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  • 1.
    Abelius, M
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Nilsson, L J
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Immunological interactions between mother and child: a characterisation of Th1-and Th2-like chemokines during pregnancy, postpartum and childhood in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 170-1712011Ingår i: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, nr 2, s. 170-171Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 2.
    Abelius, Martina S
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    High cord blood levels of the T-helper 2-associated chemokines CCL17 and CCL22 precede allergy development during the first 6 years of life2011Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, nr 5, s. 495-500Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1- and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life.

  • 3.
    Abelius, Martina S
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Janefjord, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Helsingborg Hospital, Helsingborg.
    Duchén, Karel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Nilsson, Lennart J
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Allergicentrum US.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity2015Ingår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 73, nr 5, s. 445-459Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PROBLEM: How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear.

    METHOD OF STUDY: Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring.

    RESULTS: Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P < 0.001) and IL-5 expression in PBMC with fetal galectin1 (ρ = 0.91, P < 0.001). Increased expression of Th2-associated CCL22 in CBMC preceded allergy development.

    CONCLUSIONS: Gene expression locally and systemically during pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development.

  • 4.
    Abelius, Martina S
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Janefjord, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Duchén, Karel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women2014Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background: The influence of maternal allergy on the development of immune responses and allergy in the offspring is not understood.

    Objective: To investigate (i) if maternal allergy influences the gene expression locally in placenta, systemically in peripheral blood mononuclear cells (PBMC) and fetally in cord blood mononuclear cells (CBMC), (ii) if the gene expression in the placenta and PBMC influences the gene expression in CBMC and (iii) how the gene expression at birth relates to allergy development during  childhood.

    Methods: A real-time PCR array was used to quantify forty immune regulatory genes in placenta, PBMC (gestational week 39) and in CBMC from 7 allergic and 12 non-allergic women and their offspring. Furthermore, quantitative real-time PCR was used to measure mRNA expression of Tbx21, GATA-3, Foxp3, RORC and CCL22 in CBMC, selected based on present PCR array results and previous protein findings in cord blood, in 13 children who developed and 11 children who did not develop allergy during childhood.

    Results: The gene expression profile in the placenta revealed a T-helper (Th) 2-/anti-inflammatory environment as compared with gene expression systemically, in PBMC. Maternal allergy was associated with increased expression of p35 in PBMC and CBMC and p40 in placenta. Placental p35 expression correlated with fetal Tbx21 expression (Rho=-0.88, p<0.001) and maternal IL-5 expression in PBMC with fetal Galectin-1 (Rho=0.91, p<0.001) expression. Allergy development in the children was preceded by high mRNA expression of the Th2-associated chemokine CCL22 at birth.

    Conclusion and clinical relevance: Gene expression locally and systemically during pregnancy influenced the offspring’s gene expression at birth, indicating an interplay between maternal and fetal immunity. Children developing allergy during childhood had an increased expression of the Th2-associated chemokine CCL22 at birth, indicating a Th2 skewing before disease onset. Maternal allergy was not associated with a Th2-dominance in placenta, PBMC or CBMC.

  • 5.
    Abelius, Martina S
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Lempinen, Esma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Lindblad, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy2014Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, nr 4, s. 387-393Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The influence of the intra-uterine environment on the immunity and allergy development in the offspring is unclear. We aimed to investigate (i) whether the pregnancy magnifies the Th2 immunity in allergic and non-allergic women, (ii) whether the maternal chemokine levels during pregnancy influenced the offspring’s chemokine levels during childhood and (iii) the relationship between circulating Th1/Th2-associated chemokines and allergy in mothers and children.

    Methods: The Th1-associated chemokines CXCL9, CXCL10, CXCL11, and the Th2- associated chemokines CCL17, CCL18 and CCL22 were quantified by Luminex and ELISA in 20 women with and 36 women without allergic symptoms at gestational week (gw) 10–12, 15–16, 25, 35, 39 and 2 and 12 months post-partum and in their children at birth, 6, 12, 24 months and 6 yr of age. Total IgE levels were measured using ImmunoCAP Technology.

    Results: The levels of the Th2-like chemokines were not magnified by pregnancy. Instead decreased levels were shown during pregnancy (irrespectively of maternal allergy status) as compared to post-partum. In the whole group, the Th1-like chemokine levels were higher at gw 39 than during the first and second trimester and post-partum. Maternal CXCL11, CCL18 and CCL22 levels during and after pregnancy correlated with the corresponding chemokines in the offspring during childhood. Increased CCL22 and decreased CXCL10 levels in the children were associated with sensitisation and increased CCL17 levels with allergic symptoms during childhood. Maternal chemokine levels were not associated with maternal allergic disease.

    Conclusions: Allergic symptoms and sensitisation were associated with decreased Th1-and increased Th2-associated chemokine levels during childhood, indicating a Th2 shift in the allergic children, possibly influenced by the maternal immunity during pregnancy.

  • 6.
    Berg, Göran
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ekerfelt, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Hammar, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Lindgren, R
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi.
    Matthiesen, Leif
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Cytokine changes in postmenopausal women treated with estrogens: A placebo-controlled study2002Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem: Hormone replacement therapy (HRT) is being increasingly used in postmenopausal women. Sex steroids are known to affect the immune system in several ways, although this is mainly based on clinical observations and experimental studies. Method of study: We studied the in vivo effects of transdermal estrogens (50 ╡g 17 ▀-Estradiol/24 hr) on cytokine production in postmenopausal women. A total of 17 women were randomized to either placebo (n = 7) or active estrogen therapy (n = 10) for 14 weeks, with addition of oral medoxyprogesterone acetate 10 mg daily during the last 2 weeks in both groups. Secretion of the cytokines IFN-?, IL-4, IL-10 and IL-6 in blood mononuclear cells was determined, spontaneously and after stimulation with common vaccination antigens and mitogen, using the cell ELISA technique. Results: IL-6 production after stimulation with purified protein derivate (PPD) decreased in the estrogen treated group (P < 0.01). Mitogen-induced IL-6 production was reduced in the estrogen treated group in contrast to an increase in the placebo group, leading to a significant difference (P < 0.01) between the groups after 12 weeks of treatment. This difference was eliminated after an addition of progestagens for 2 weeks. No significant changes were noted for IFN-?, IL-4 or IL-10 in relation to estrogen or placebo treatment. Conclusions: In the present controlled study, the main in vivo effect of estrogens was a decrease in IL-6 production, indicating a possible beneficial effect of estrogen therapy.

  • 7.
    Boij, R
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Nilsson-Ekdahl, K
    Uppsala University.
    Svensson, J
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Sandholm, K
    Linneus University.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Palonek, E
    Karolinska University.
    Jarle, M
    Karolinska University.
    Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 94, issue 1, pp 109-1092012Ingår i: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2012, Vol. 94, nr 1, s. 109-109Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 8.
    Boij, Roland
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. County Hospital Ryhov, Sweden.
    Mjosberg, Jenny
    Karolinska Institute, Sweden.
    Svensson Arvelund, Judit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Hjorth, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Helsingborg Hospital, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia2015Ingår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, nr 4, s. 368-378Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Objective Utilizing recent advances in flow cytometry phenotyping, we aimed to assess whether a deficiency of Treg subpopulations occurs in preeclampsia. Method of study Six-color flow cytometry was used for Treg phenotyping in 18 preeclamptic women (one early-onset, one severe and 16 both), 20 women with normal pregnancy, and 20 non-pregnant controls. Results No differences were found in major Treg populations including CD127(low)CD25(+)/CD127(ow)FOXP3(+), resting (FOXP3(dim)CD45RA(+)), and activated (FOXP3(bright)CD45RA(-)) Treg cells, whereas preeclamptic women showed increased CTLA-4(+) and CCR4(+) proportions within resting/activated Treg populations. Corticosteroid treatment prior to blood sampling (n = 10) affected the distribution of Treg populations. Conclusions Although we found no major alterations in circulating Treg frequencies, differences in CTLA-4(+) and CCR4(+) frequencies suggest a migratory defect of Treg cells in preeclampsia. Corticosteroid treatment should be taken into account when evaluating Treg cells.

  • 9.
    Boij, Roland
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Svensson, Judit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson-Ekdahl, Kristina
    Uppsala University, Sweden Linneaus University, Sweden .
    Sandholm, Kerstin
    Linneaus University, Sweden .
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Palonek, Elzbieta
    Karolinska University Hospital, Sweden Doping Control Lab, Sweden .
    Garle, Mats
    Karolinska University Hospital, Sweden Doping Control Lab, Sweden .
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia2012Ingår i: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 1046-7408, Vol. 68, nr 3, s. 258-270Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem Although preeclampsia has been associated with inflammation, coagulation, and angiogenesis, their correlation and relative contribution are unknown. Method of Study About 114 women with preeclampsia, 31 with early onset (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls were included. A broad panel of 32 biomarkers reflecting coagulation, inflammation, and angiogenesis was analyzed. Results Preeclampsia was associated with decreased antithrombin, IL-4 and placental growth factor levels and with increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in the preeclampsia and EOP group than in controls, respectively. No correlations between the biomarkers were found in preeclampsia. Multivariate logistic regression tests confirmed the results. Conclusions Cytokines, chemokines and complement activation seem to be part of a Th1-like inflammatory reaction in preeclampsia, most pronounced in EOP, where chemokines may be more useful than cytokines as biomarkers. Biomarkers were not correlated suggesting partly independent or in time separated mechanisms.

  • 10.
    Ekerfelt, Christina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Lidström, Charlotte
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Sharma, Surendra
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Spontaneous secretion of interleukin-4, interleukin-10 and interferon-gamma by first trimester decidual mononuclear cells2002Ingår i: American Journal of reproductive immunology, ISSN 8755-8920, Vol. 47, nr 3, s. 159-166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PROBLEM: A T-helper cell type 2 (Th2) cytokine dominated microenvironment has been predicted to be crucial for successful pregnancy. However, little information is available about local cytokine secretion in the human decidua. We determined the spontaneous secretion of interleukin-4 (IL-4), interferon-γ (IFN-γ) and IL-10 by decidual mononuclear cells at the single cell level and compared it with their secretion by peripheral blood mononuclear cells (PBMC) in the first trimester of pregnancy.

    METHODS OF STUDY: The cytokine secretion from decidual and blood cells was detected by a sensitive enzyme-linked immunosorbent spot-forming cell (ELISPOT)-assay.

    RESULTS: Cells secreting IL-4 (median 153, range 8–530), IL-10 (median 188, range 32–1600) and IFN-γ (median 123, range 15–1140) were detected in all decidual and blood samples. The cytokine secretion showed a co-linear pattern in both the blood and decidua, i.e. when one cytokine was secreted at high levels, the others followed the trend. No correlation was found between the number of cytokine secreting cells in blood and decidua for any of the cytokines.

    CONCLUSIONS: Interleukin-4 and IL-10 are locally secreted in the decidua early during normal pregnancy, probably counteracting the fetal rejecting effects of co-expressed IFN-γ. The cytokine secretion by blood cells does not generally reflect the local secretion pattern during first trimester pregnancy.

  • 11.
    Ekerfelt, Christina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Mathiesen, Leif
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Berg, Göran
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Th2-deviation of fetus-specific T cells1999Ingår i: Immunology today (Amsterdam. Regular ed.), ISSN 0167-5699, E-ISSN 1355-8242, Vol. 20, s. 534-534Artikel i tidskrift (Refereegranskat)
  • 12.
    Ernerudh, Jan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Forsberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Straka, E
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Johansson, Ewa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Bhai Mehta, Ratnesh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Svensson, J
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Boij, R
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Mjösberg, Jenny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    T helper cells and T helper cell plasticity in pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 131-1312011Ingår i: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, nr 2, s. 131-131Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 13.
    Gustafsson (Lidström), Charlotte
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Hummerdal, Pernilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Cytokine secretion in decidual mononuclear cells from term human pregnancy with or without labour: ELISPOT detection of IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha2006Ingår i: Journal of reproductive immunology, ISSN 0165-0378, Vol. 71, nr 1, s. 41-56Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cytokines are believed to be important in maintaining pregnancy and in the process of labour induction in humans. The aim of this study was to investigate the secretion of the cytokines interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-10, transforming growth factor-β (TGF-β) and tumour necrosis factor-α (TNF-α) in decidual tissue with or without labour.

    Decidual tissue was collected from 32 healthy women undergoing elective caesarean sections before the onset of labour (n = 17) or after normal vaginal delivery (n = 15). Mononuclear cells were analysed for cytokine secretion with ELISPOT. To validate the widely used method of tissue collected at caesarean sections and after vaginal deliveries as a representative of before and after labour, respectively, placenta biopsies were collected from 12 healthy women to study the expression of the prostaglandin pathway enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase (mPGES).

    Decidual mononuclear cells from term human pregnancy spontaneously secrete IFN-γ, IL-4, IL-10, TGF-β and TNF-α. No difference was seen in cytokine secretion with or without labour, indicating that decidual leukocytes are not the main cell population responsible for plausible cytokine regulation in the process of termination of pregnancy. Placental tissues obtained after vaginal delivery showed a higher mRNA expression of the prostaglandin regulating molecules COX-2 and mPGES than tissues from caesarean sections before the onset of labour, validating that the model can be used as a representative of the state before and after labour.

  • 14.
    Gustafsson (Lidström), Charlotte
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Mjösberg, Jenny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Matussek, Andreas
    Department of Clinical Microbiology, County Hospital Ryhov, Jönköping, Sweden.
    Geffers, Robert
    Mucosal Immunity, Helmholtz Centre for Infection Research (HCI), Braunschweig, Germany.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Sharma, Surendra
    Department of Pediatrics, Brown University and Women and Infants' Hospital of Rhode Island, Providence, Rhode Island, United States of America.
    Buer, Jan
    Institute of Medical Microbiology, University Hospital Essen, Essen, Germany.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Gene expression profiling of human decidual macrophages: Evidence for immunosuppressive phenotype2008Ingår i: PLoS ONE, ISSN 1932-6203, Vol. 3, nr 4, s. e2078-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known.

    Methodology/Principal Findings: Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications.

    Conclusions/Significance: The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.

  • 15.
    Jablonowska, Barbara
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Palfi, Miodrag
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Transfusionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Selbing, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Kjellberg, Svante
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    T and B lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment2002Ingår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 48, nr 5, s. 312-318Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Jablonowska B, Palfi M, Matthiesen L, Selbing A, Kjellberg S, Ernerudh J. T and B Lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment. AJRI 2002; 48:312–318 © Blackwell Munksgaard, 2002

    PROBLEM: To investigate circulating lymphocyte subsets in women with recurrent spontaneous abortion (RSA) in relation to pregnancy outcome and to treatment with intravenous immunoglobulin (IVIG).

    METHOD OF STUDY: Forty-one women with a history of unexplained RSA were examined during first trimester of pregnancy before IVIG or placebo treatment and after pregnancy. The results were compared with five healthy, non-pregnant women and five women in the first trimester of normal pregnancy. Circulating lymphocyte subsets with focus on T-cell subpopulations were determined by flow cytometry.

    RESULTS:  The proportions of human leukocyte antigen (HLA)-DR positive T cells (CD3+ HLA-DR+), T-killer/effector cells (CD8+ S6F1+) and B cells (CD19+) were increased, whereas the proportion of T-suppressor/inducer cells (CD4+ CD45RA+) was decreased during first trimester pregnancy of RSA women compared with pregnant normal controls. T and B lymphocyte subsets did not correlate with pregnancy outcome on either IVIG or placebo group.

    CONCLUSIONS: In RSA patients, the immune system seems to be activated in contrast to the suppression noted in normal pregnancy.

  • 16.
    Jonsson, Yvonne
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Nieminen, Katri
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Indications of an altered immune balance in preeclampsia: A decrease in in vitro secretion of IL-5 and IL-10 from blood mononuclear cells and in blood basophil counts compared with normal pregnancy2005Ingår i: Journal of Reproductive Immunology, ISSN 0165-0378, Vol. 66, nr 1, s. 69-84Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It has been suggested that maladaptation of the maternal immune response during pregnancy might be a causal factor for preeclampsia. This study was designed to examine the systemic immune status at both the innate level and the adaptive level in pregnancies complicated by preeclampsia (n = 15) and normal pregnancies (n = 15). Spontaneous and in vitro-induced secretion of IL-5, IL-6, IL-10, IL-12, IL-13 and TNF-α, in response to paternal blood cells and the vaccination antigens purified protein derivate of tuberculin (PPD) and tetanus toxoid (TT), was detected in cell culture supernatants from blood mononuclear cells by ELISA. Preeclamptic women showed reduced numbers of basophil granulocytes in the blood (p = 0.004) and lower spontaneous secretion of IL-5 from blood mononuclear cells (p = 0.016). In addition, paternal antigen-induced secretion of IL-10 was decreased in preeclampsia compared with normal pregnancy (p = 0.012). No further differences between preeclampsia and normal pregnancy were found for any stimuli or cytokines. The present findings of reduced basophil numbers and lower spontaneous in vitro secretion of IL-5 in preeclampsia compared with normal pregnancy indicate a decrease in systemic Th2 immunity in preeclampsia. Furthermore, the decrease in paternal antigen-induced secretion of the immunosuppressive cytokine IL-10 in preeclampsia indicates a fetus-specific decrease in immunosuppression mediated by blood mononuclear cells. Whether these systemic changes are a cause or a consequence of preeclampsia remains to be elucidated.

  • 17.
    Jonsson, Yvonne
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Rubér, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Nieminen, Katri
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Sharma, Surendra
    Departments of Pediatrics and Pathology, Brown University and Women and Infants’ Hospital of Rhode Island, Providence, RI, USA.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Cytokine mapping of sera from women with preeclampsia and from women with normal pregnancies2006Ingår i: Journal of Reproductive Immunology, ISSN 0165-0378, Vol. 70, nr 1-2, s. 83-91Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction

    Preeclampsia is a pregnancy-specific syndrome. The immune system in preeclampsia is changed with an increased innate activity and there is a hypothesis of a shift towards Th1-type immunity. The aim of this study was to determine a spectrum of soluble immunological factors denoting different aspects of immune activation in third trimester sera from women with preeclampsia (N = 15) and compare with levels in sera from normal pregnant women (N = 15).

    Material and methods

    IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFN-α, IFN-γ, TNF-α, GM-CSF, MIP-lα, MIP-1β, MCP-1, eotaxin and RANTES were measured in serum using multiplex bead arrays. The levels of soluble CD14 and soluble IL-4 receptor were measured by enzyme-linked immunoassay (ELISA).

    Results

    Preeclamptic women had significantly increased levels of circulating IL-6 (p = 0.002), IL-8 (p = 0.003) and soluble IL-4R (p = 0.037), compared to women with normal pregnancies.

    Conclusion

    This study supports the hypothesis of increased inflammatory responses in preeclampsia, illustrated by the increased levels of IL-6 and IL-8. The finding of increased levels of soluble IL-4 receptor is an intriguing finding with several interpretations, which may partly support the hypothesis of a Th1 shift in preeclampsia.

  • 18.
    Lidström Gustafsson, Charlotte
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Sharma, Surendra
    Department of Pediatrics & Department of Pathology, Brown University and Women and Infants' Hospital of Rhode Island, Providence, RI, USA.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Cytokine secretion patterns of NK cells and macrophages in early human pregnancy decidua and blood: Implications for suppressor macrophages in decidua2003Ingår i: American Journal of reproductive immunology, ISSN 8755-8920, Vol. 50, nr 6, s. 444-452Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem: Local immune modulation has been shown to be of considerable importance for the maintenance of successful pregnancy. We have previously reported the secretion of interferon-γ (IFN-γ), interleukin-4 (IL-4) and IL-10 in human decidua from early normal pregnancy. The aim of this study was to investigate the cellular source of cytokine secretion in the decidua, and compare this to secretion patterns in peripheral blood.

    Method of study: Decidual tissue and peripheral blood was collected from 20 women undergoing surgical abortion during first trimester pregnancy. Monocytes/macrophages and NK cells were enriched by immunomagnetic cell separation and cytokine secretion was detected by enzyme-linked immunosorbent spot-forming cell assay.

    Results: Decidual and peripheral monocytes/macrophages and NK cells spontaneously secrete IFN-γ, IL-4 and IL-10. The number of IL-10 secreting cells was significantly higher in decidual macrophages compared with decidual non-monocytic cells as well as compared with blood monocytes/macrophages. These differences were not seen for IFN-γ or IL-4.

    Conclusions: Our results indicate that decidual macrophages subserve important suppressive functions in the pregnant uterus.

  • 19.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Letter: Reply to Do dose-related mechanisms exist for the angiogenic behaviours of heparin derivatives?, Yavuc C, Karahan O.2012Ingår i: American Journal of Reproductive Immunology and Microbiology, ISSN 8755-8920, Vol. 68, nr 3, s. 187-188Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 20.
    Matthiesen, Leif
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Berg, Göran
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Jonsson, Yvonne
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Sharma, Surendra
    Department of Pediatrics and Pathology, Women and Infants Hospital of Rhode Island, Brown University, Providence, R.I., USA.
    Immunology of preeclampsia2005Ingår i: Immunology of Pregnancy / [ed] Markert U.R. (Jena), Basel, Switzerland: S. Karger, 2005, Vol. 89, s. 49-61Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-α and interferon-γ. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.

  • 21.
    Matthiesen, Leif
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Berg, Göran
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Håkansson, L
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Lymphocyte subsets and mitogen stimulation of blood lymphocytes in preeclampsia.1999Ingår i: American Journal of Reproductive Immunology and Microbiology, ISSN 8755-8920, Vol. 41, s. 192-203Artikel i tidskrift (Refereegranskat)
  • 22.
    Matthiesen, Leif
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Berg, Göran
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Skogh, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Reumatologi. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    A prospective study on the occurrence of autoantibodies in low-risk pregnancies. 1999Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 83, s. 21-26Artikel i tidskrift (Refereegranskat)
  • 23.
    Matthiesen, Leif
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Khademi, Mohsen
    Ekerfelt, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sharma, Surendra
    Olsson, Tomas
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    In-situ detection of both inflammatory and anti-inflammatory cytokines in resting peripheral blood mononuclear cells during pregnancy2002Ingår i: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 58, nr 1, s. 49-59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Local and possibly systemic curtailment of the maternal immune response is important for a successful pregnancy. Although the local milieu at the utero-placental interface is likely to harbor the most prominent alterations, it is suggested, at least in mice, that systemic immunity is also tolerized during pregnancy. In the present study, we investigated mRNA expression of the key immunomodulatory cytokines, interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-a and interferon (IFN)-? during normal pregnancy. Material and methods: In-situ hybridization (ISH) of cytokine mRNA in resting peripheral blood mononuclear cells (PBMCs) was used to detect the number of cells spontaneously expressing cytokines. Eleven women with normal gestations were followed during pregnancy as well as 8 weeks postpartum, and compared with 10 non-pregnant healthy controls. Results: The numbers of IFN-? and IL-4 mRNA expressing cells were found to be significantly increased during pregnancy and postpartum compared with non-pregnant controls. Pregnant women and non-pregnant controls did not differ in their expression of TNF-a and IL-10. Conclusion: Our studies demonstrated increased numbers of both IFN-? and IL-4 mRNA expressing cells in blood suggesting that systemic immunomodulation, albeit partial, takes place during normal pregnancy. It is proposed that enhanced IL-4 expression, possibly in concert with other elevated anti-inflammatory immunomodulatory cytokines, curtail the potentially hazardous effects of IFN-? on systemic immunity during pregnancy.

  • 24.
    Mjösberg, Jenny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Boij, Roland
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Jenmalm, Maria C.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Circulating CD4dimCD25highFOXP3+ regulatory T cells in severe early-onset preeclampsiaManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Preeclampsia is an inflammatory condition suggested to involve regulatory CD4+CD25high T helper cell (Treg) disturbances. However, the importance of Tregs in early-onset preeclampsia, associated with increased disease severity and possibly representing a more distinct placental disease, remains unclear. We recently showed that by defining Tregs as CD4dimCD25high cells, the risk of including activated non-Tregs, being more prominent in the circulation during pregnancy, is avoided. The aim of this study was to determine, using updated Treg markers and flow cytometric gating strategies, the frequency and phenotype of circulating Tregs from women with severe early-onset preeclampsia (n=10) as compared with healthy pregnant (n=20) and nonpregnant (n=20) women. The frequency of CD4dimCD25high cells and the expression of FOXP3 was similar in healthy and preeclamptic pregnancy. However, the occurrence of CTLA-4+ and HLA-DR+ cells in the Treg population from preeclamptic women tended to be higher than in healthy pregnant women, indicating alterations in Treg functionality in preeclampsia. Further, the Treg population from healthy pregnant, but not preeclamptic, women tended to be enriched for CCR4+ and CD45R0+ cells as compared with nonpregnant women. In conclusion, although the findings do not support a role for diminished circulating Treg frequency in severe early-onset preeclampsia, the study suggests functional alterations related to Treg suppression, activation and migration mechanisms in this subgroup of preeclamptic women.

  • 25.
    Palfi, Miodrag
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Transfusionsmedicin. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Hildén, Jan-Olof
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Transfusionsmedicin. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Matthiesen, Leif
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Selbing, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Berlin, Gösta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Transfusionsmedicin. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    A case of severe Rh (D) alloimmunization treated by intensive plasma exchange and high-dose intravenous immunoglobulin2006Ingår i: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 35, nr 2, s. 131-136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In extremely severe Rh (D) alloimmunization, during pregnancy, early diagnosis and treatment is essential to avoid hydrops fetalis. Intrauterine transfusion (IUT) is of utmost importance in the prevention of fetal anemia but it is usually feasible only after 20 weeks of pregnancy. Therefore, additional treatment options in early pregnancy are needed. Study design and methods: A 27-year-old severely D + C immunized woman was admitted at 8 weeks of gestation in her fifth pregnancy with an extremely high concentration of anti-D. Her first pregnancy was uneventful but resulted in D + C alloimmunization. The next two pregnancies were unsuccessful, because of hydrops fetalis resulting in fetal death in pregnancy week 20 and 24, respectively, despite treatment with high-dose intravenous immunoglobulin (IVIG) and IUT treatment. A fourth pregnancy was terminated with legal abortion. The patient was eager and persistent to accomplish a successful pregnancy. Therefore, a combination of treatments consisting of plasma exchange (PE) three times/week and IVIG 100 g/week was started in pregnancy week 12. PE was performed 53 times and totally 159 L of plasma was exchanged. Results: The anti-D concentration was 12 μg/mL (IAT titer 2000) before start of treatment by PE and IVIG in pregnancy week 12. The concentration of anti-D was gradually reduced to approximately 3 μg/mL after only two weeks of treatment and was maintained at that level until pregnancy week 22. In pregnancy week 26 and 27, signs of hydrops were detected by ultrasonography and IUT were performed at each occasion. Sectio was inevitable at pregnancy week 28 + 1 and a male baby was born: Hb 58 g/L (cord sample) and 68 g/L (venous sample), weight 1385 g, Apgar score = 4-5-7, Bilirubin 56-150 mmol/L (4 h). Exchange transfusion was performed on day two and day five. Phototherapy was also implemented for eight days. The newborn's recovery thereafter was uneventful and complete. Conclusion: A combination of PE and IVIG may be an efficient treatment possible to start in early pregnancy in patients with extremely severe Rh (D) alloimmunization, with a history of hydrops fetalis in previous pregnancies. © 2006 Elsevier Ltd. All rights reserved.

  • 26.
    Palfi, Miodrag
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Transfusionsmedicin. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Jablonowska, Barbara
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Matthiesen, Leif
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Circulating interferon-gamma- and interleukin-4 - secreting cells in recurrent spontaneous abortions. 1999Ingår i: American Journal of Reproductive Immunology and Microbiology, ISSN 8755-8920, Vol. 41, s. 257-263Artikel i tidskrift (Refereegranskat)
  • 27.
    Persson, Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Jonsson, Yvonne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Sandberg, Martina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Hälsouniversitetet.
    Increased circulating paternal antigen-specific IFN-γ- and IL-4-secreting cells during pregnancy in allergic and non-allergic women2008Ingår i: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 79, nr 1, s. 70-78Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Allergic women have been reported to give birth to more children than non-allergic women, speculatively explained by the former's predisposition for Th2 polarization, possibly favoring pregnancy.

    AIM: The aim of this study was to test the hypothesis that allergy is associated with more Th2-deviated responses to paternal antigens throughout pregnancy.

    METHODS: Blood samples were collected on six occasions during pregnancy and two occasions postpartum (pp). Of the 86 women initially included, 54 women had a normal pregnancy and completed the sampling procedures. Eleven women fulfilled the strict criteria for allergy (allergic symptoms and circulating IgE antibodies to inhalant allergens) and 23 were strictly non-allergic (non-sensitized without symptoms). The numbers of blood mononuclear cells secreting IFN-gamma and IL-4, spontaneously and in response to paternal alloantigens, were compared between the groups.

    RESULTS: The numbers of spontaneously as well as paternal antigen-induced IFN-gamma- and IL-4-secreting cells were similar in allergic and non-allergic pregnant women on all occasions. A similar increase in the numbers of both IFN-gamma- and IL-4-secreting cells were found in allergic and non-allergic women during pregnancy, both regarding spontaneous and paternal antigen-induced secretion.

    CONCLUSIONS: This study does not support the hypothesis of a more pronounced Th2-deviation to paternal antigens in allergic pregnant women compared with non-allergic pregnant women, as measured by number of cytokine-secreting cells. The observed increase of both IFN-gamma- and IL-4-secreting cells during normal pregnancy may be interpreted as a Th2-situation, since the effects of IL-4 predominate over the effects of IFN-gamma.

  • 28. Plevyak, M
    et al.
    Hanna, N
    Mayer, S
    Murphy, S
    Pinar, H
    Fast, L
    Ekerfelt, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Sharma, S
    Deficiency of decidual IL-10 in first trimester missed abortion: A lack of correlation with the decidual immune cell profile2002Ingår i: American Journal of Reproductive Immunology and Microbiology, ISSN 8755-8920, Vol. 47, nr 4, s. 242-250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PROBLEM: To determine if first trimester missed abortion decidua is characterized by an altered immune cell profile and/or a modified interleukin (I L)-10 and interferon (IFN)-gamma production pattern compared with decidua from elective termination. METHOD OF STUDY: Flow cytometry and immunohistochemistry techniques were used to determine the decidual immune cell phenotypic profile and production pattern of IL-10 and IFN-gamma in cases of elective termination (n = 14) and missed abortion (n = 12). RESULTS: Both groups had a similar proportion of CD56(+) CD16(-),CD56(+) CD16(+), CD19(+), CD3(+), CD4(+), CD8(+), alphabeta T cells and gammadelta T cells. The majority of alphabeta and gammadelta positive T cells in both groups coexpressed the natural killer (NK) cell marker CD56, but lacked cell surface expression of CD3. Diminished decidual IL-10 staining was noted in 7/10 missed abortion cases compared with none of the elective termination cases (n = 12) (P = 0.007). A uniform decidual IFN-gamma staining pattern was observed in both groups. CONCLUSION: Decreased IL-10 production coupled with a sustained IFN-gamma presence noted in missed abortion compared with elective termination cases suggest that these cytokines may be important determinants in pregnancy outcome. In contrast, differences in the proportion of immune cells between both groups may not be a critical factor in early pregnancy loss. In normal pregnancy, decidual alphabeta and gammadelta positive T cells with reduced CD3 on their cell surface may be intrinsically restricted in T-cell receptor (TCR)-mediated activation.

  • 29.
    Sandberg, Martina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Frykman, Anne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Cord blood cytokines and chemokines and development of allergic disease2009Ingår i: PEDIATRIC ALLERGY AND IMMUNOLOGY, ISSN 0905-6157, Vol. 20, nr 6, s. 519-527Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exposure to ubiquitous allergens early in life, even before birth, may influence the incidence of allergic diseases later in life. During pregnancy, the fetomaternal interface is surrounded by high levels of T-helper (Th)2-like cytokines, possibly favouring the development of Th2-like immune responses in the offspring. The aim of this study was to evaluate the relation between cord blood (CB) IgE antibodies, Th1- and Th2-like cytokines and chemokines, maternal allergy and development of allergic disease during the first 2 yr of life in the offspring. The CB cytokine and chemokine levels from children of 20 allergic and 36 non-allergic women were determined by a multiplexed Luminex assay and ELISA. Total CB and maternal IgE antibody concentrations were quantified using ImmunoCAP technology. The maternal IgE levels during and after pregnancy correlated with CB IgE and Th2-associated macrophage-derived chemokine [MDC (CCL22)] levels. Development of allergic disease and sensitization was associated with increased CB IgE and MDC (CCL22) levels, as well as high ratios of MDC (CCL22) to Th1-associated interferon-gamma inducible protein 10 [IP-10 (CXCL10)] and interferon-gamma inducible T-cell alpha-chemoattractant [I-TAC (CXCL11) (n = 7 allergic vs. n = 25 non-allergic)]. The correlations between maternal IgE and CB IgE and MDC (CCL22) levels possibly indicate that the maternal immunity can affect the Th1/Th2 profile in the neonate. Development of allergic disease is associated with a more marked Th2-like deviation already at birth, shown as increased levels of CB IgE and MDC (CCL22) and higher ratios of MDC (CCL22) to IP-10 (CXCL10) and I-TAC (CXCL11).

  • 30.
    Sandberg, Martina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Frykman, Anne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Jonsson, Yvonne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Persson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy2009Ingår i: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 0165-0378, Vol. 81, nr 1, s. 82-88Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type 2 T-helper cell (Th2)-skewed immunity is associated with successful pregnancy and the ability to easily direct immune responses to a Th2-polarised profile may be an evolutionary benefit. The Th2-like immunity associated with allergic disease might generate favourable effects for the maintenance of pregnancy, but could also promote development of Th2-like immune responses and allergic disease in the offspring. The aim of this study was to explore, by using IgE as a stable proxy for Th2, the Th1/Th2 balance in allergic and non-allergic women by measuring allergen-specific and total IgE antibody levels in plasma during pregnancy and after delivery. Specific and total IgE antibody levels were determined by ImmunoCAP technology at five occasions during pregnancy (gestational weeks 10-12, 15-16, 25, 35 and 39), as well as at 2 and 12 months after delivery. Thirty-six women without and 20 women with allergic symptoms were included, of whom 13 were sensitised with allergic symptoms and 30 were non-sensitised without allergic symptoms. The levels of total IgE, but not allergen-specific IgE, were increased during early pregnancy when compared to 12 months after delivery in the sensitised women with allergic symptoms, but not in the non-sensitised women without allergic symptoms (pandlt;0.01). This increase in total IgE levels during early pregnancy only in the sensitised women with allergic symptoms indicates that allergy is associated with an enhanced Th2 deviation during pregnancy.

  • 31.
    Sharma, Surendra
    et al.
    Brown University.
    Stabila, Joan
    Brown University.
    Pietras, Linda
    Brown University.
    Singh, Arvind R
    Brown University.
    McGonnigal, Bethany
    Brown University.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Padbury, James F
    Brown University.
    Haplotype-dependent Differential Activation of the Human IL-10 Gene Promoter in Macrophages and Trophoblasts: Implications for Placental IL-10 Deficiency and Pregnancy Complications2010Ingår i: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 1046-7408, Vol. 64, nr 3, s. 179-187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem Polymorphic changes in the IL-10 gene promoter have been identified that lead to altered IL-10 production. We hypothesized that because of these genotypic changes, the IL-10 promoter might be expressed in a cell type-specific manner and may respond differentially to inflammatory triggers. Method of study We created reporter gene promoter constructs containing GCC, ACC, and ATA haplotypes using DNA from patients harboring polymorphic changes at -1082 (G -andgt; A), -819 (C -andgt; T), and -592 (C -andgt; A) sites in the IL-10 promoter. These individual luciferase reporter constructs were transiently transfected into either primary term trophoblasts or THP1 monocytic cells. DNA-binding studies were performed to implicate the role of the Sp1 transcription factor in response to differential promoter activity. Results Our results suggest that the GCC promoter construct was activated in trophoblast cells in response to lipopolysaccharide (LPS), as demonstrated by reporter gene expression, but not in monocytic cells. The ACC construct showed weaker activation in both cell types. Importantly, while the ATA promoter was constitutively activated in both cell types, its expression was selectively repressed in response to LPS, but only in trophoblasts. DNA-nuclear protein binding assays with nuclear extracts from LPS treated or untreated cells suggested a functional relevance for Sp1 binding differences at the -592 position. Conclusions These results demonstrate cell type-specific effects of the genotypic changes in the IL-10 gene promoter. These responses may be further modulated by bacterial infections or other inflammatory conditions to suppress IL-10 production in human trophoblasts.

  • 32.
    Skamris Matthiesen, Leif
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Immune Changes in Pregnancy: A Survey of some Immunological Variables in Normal and Complicated Pregnancies1998Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The maternal systemic immune response during pregnancy is only fragmentarily understood. An adequate immune response to the gestational product is of vital importance for a successful pregnancy. Research in the field of reproductive immunology could clarify whether there is a difference between the immune responses in women with normal pregnancies and women with complicated pregnancies.

    The present thesis is a survey of selected immunological variables in non-pregnant women and in women with uncomplicated and complicated pregnancies. This was done by studying Jymphocyte populations, the proliferative capacity of lymphocytes as stimulated with mitogcns and immunomodulating drugs, the presence of iL-4 and JFN-g secreting cells, and the presence of certain autoantibodies in a low-risk pregnant population.

    Normal pregnancies were characterised by decreased levels of B cells (CD19+),_ NK cells (CD56+), expression of the IL-2 Receptor on lymphocytcs (CD25+) as well as HLA-DR+ on T cells (CD3+) and increased level of inactivated CD4+CD45RA+ T cells. Increased levels of NK cells, expression ofHLA-DR on T cells and antigen activated CD4+CD45R0+ T cells was found in preeclamptic patients compared with normal pregnancies. Thus, the immunosuppression that was found in normal pregnancies was not seen in pregnancies complicated by prccclampsia.

    Addition ofmitogens to cell cultures in either autologous or AB serum culture media demonstrated the existence of serum and cell mediated suppressor activity. The lymphoprolifcrative response to mitogens was reduced during nmmal pregnancies, possibly mediated by PGE2 and the presence ofT lymphocytes with suppressor function. The lymphoproliferative response in pregnancies complicated with severe precclampsia was further reduced as compared with normal pregnancies.

    Circulating IFN-g and IL-4 secreting cells increased during nonnal pregnancies. By the use of a mixed lymphocyte culture test it was found that paternal lymphocytes as stimulator-cells generated an elevated IL-4 secretion from maternal responder cells. These results indicate that the maternal immune response is shifted towards humoral immunity (TH2) by the recognition of the paternal allo-antigens, possibly to avoid maternal allo-reactivity against the fetus. The present findings also indicate that cell-mediated immunity (THl) to antigens were allowed to occur.

    The prevalence of anticardiolipin antibodies (aCL, IgG, ELISA), antinuclear antibodies (ANA, Indirect immunofluorescence) and rheumatoid factor (RF, agglutination test) in a low-risk pregnant population was low. However, there was an association, albeit weak, between ANA and women with preeclampsia.

    In summary, the maternal systemic immune response is characterised by suppression and non-aggression in nmmal human pregnancies. In women with pregnancy complications, such as preeclampsia, this suppression and inactivation is only partially achieved.

  • 33.
    Uustal Fornell, Eva K.
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Haalböök, Olof
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Linköpings universitet, Hälsouniversitetet.
    Matthiesen, Leif S.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Sjödahl, Rune
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Linköpings universitet, Hälsouniversitetet.
    Clinical consequences of anal sphincter rupture during vaginal delivery1996Ingår i: Journal of the American College of Surgeons, ISSN 1072-7515, E-ISSN 1879-1190, Vol. 183, nr 6, s. 553-558Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Rupture of the anal sphincters at childbirth is considered rare in obstetric literature. Long-term effects are sparingly mentioned. In clinical practice, however, it is not uncommon to meet women with anal incontinence. The aim of our study was to record the incidence and to evaluate the consequences of rupture of the anal sphincter at childbirth.

    STUDY DESIGN:

    Fifty-one consecutive women with primarily sutured anal sphincter rupture and 31 women without anal sphincter rupture were prospectively studied after vaginal delivery. All were assessed clinically at 3 days, 6 weeks, and 6 months after delivery. After 6 months, all women underwent anorectal manometry and answered a questionnaire about incontinence, social function, and general health.

    RESULTS:

    The overall incidence of sphincter rupture was 2.4 percent. Significantly lower values were found for maximum anal squeeze pressure and squeeze pressure area 6 months postpartum in the women with sphincter rupture compared with those without rupture. The resting pressures did not differ between groups. Approximately 40 percent of the women in both groups had noted some fecal incontinence by 6 months postpartum. Symptoms were significantly more severe in patients with sphincter rupture.

    CONCLUSIONS:

    Anal sphincter rupture was 2.4 times as common as reported in Swedish birth statistics. The high incidence of fecal incontinence by 6 months postpartum in all women is surprising and deserves further investigation, specifically regarding occult sphincter rupture.

  • 34.
    Uustal Fornell, Eva
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Matthiesen, Leif
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Sjödahl, Rune
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Obstetric anal sphincter injury ten years after: subjective and objective long term effects2005Ingår i: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 112, nr 3, s. 312-316Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective  To establish the long term effects of obstetric anal sphincter rupture.

    Design  Prospective observational study.

    Setting  University hospital in Sweden.

    Population  Eighty-two women from a prospective study from 1990 to compare anorectal function after third degree tear.

    Methods  Women completed a structured questionnaire, underwent a clinical examination and anorectal manometry, endoanal ultrasound (EAUSG) with perineal body measurement.

    Main outcome measures  Symptoms of anal incontinence, sexual symptoms, anal manometry scores and evidence of sphincter damage on EAUSG.

    Results  Five women had undergone secondary repair and three were lost to follow up. Fifty-one women (80%) completed the questionnaire. Twenty-six out of 46 (57%) of the original study group and 6/28 (20%) of the original controls were examined. Incontinence to flatus and liquid stool was more severe in the study group than in controls. Flatus incontinence was significantly more pronounced among women with subsequent vaginal deliveries. Mean maximal anal squeeze pressures were 69 mmHg in the partial rupture group and 42 mmHg in the complete rupture group (P= 0.04). Study group women with signs of internal sphincter injury reported more pronounced faecal incontinence and had lower anal resting pressures (24 mmHg) than those with intact internal sphincters (40 mmHg) (P= 0.01). Perineal body thickness of less than 10 mm was associated with incontinence for flatus and liquid stools, less lubrication during sex and lower anal squeeze pressures (58 mmHg vs 89 mmHg, P= 0.04).

    Conclusions  Subjective and objective anal function after anal sphincter injury deteriorates further over time and with subsequent vaginal deliveries. Thin perineal body and internal sphincter injury seem to be important for continence and anal pressure.

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