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Antibodies to the Plasmodium falciparum rhoptry protein RAP-2/RSP-2 in relation to anaemia in Cameroonian children
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi. (Klavs Berzins)
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
Vise andre og tillknytning
2011 (engelsk)Inngår i: Parasite immunology (Print), ISSN 0141-9838, E-ISSN 1365-3024, Vol. 33, nr 2, s. 104-115Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Previous studies have implicated reactive antibodies to the low molecular weight rhoptry-associated proteins (RAP-1, RAP-2/RSP-2 and RAP-3) in erythroid cell destruction during Plasmodium falciparum infection. In this pilot study, the frequency, specificity and functional capacity of naturally acquired anti-RAP-2/RSP-2 antibodies were investigated in the sera of anaemic and nonanaemic malaria-infected Cameroonian children. All sera recognized RAP-2/RSP-2 by FACS, irrespective of the clinical status of the subjects. However, the anaemic children showed higher levels of IgG antibodies than the nonanaemic group, while both groups showed similar levels of IgM antibodies. Only few individuals had detectable levels of RAP-2/RSP-2-specific IgG1 and IgG3 subclass antibodies, while no IgG2 and IgG4 subclass antibodies were detected in these subjects. By ELISA, the anaemic group tended to show higher levels of antibodies to RAP-2/RSP-2 regarding all antibody classes tested, except for IgG4 and IgE. Unexpectedly, sera from the nonanaemic group activated complement to a greater extent than those from the anaemic group. These results need to be confirmed in extended studies but indicate that the effector functions of the RAP-2/RSP-2-reactive antibodies may be more important than their amounts. Such antibodies could play a role in both immunity and pathogenesis during P. falciparum infection.

sted, utgiver, år, opplag, sider
2011. Vol. 33, nr 2, s. 104-115
Emneord [en]
antibodies, complement, malarial anaemia; Rhoptry-associated protein-2 (RAP-2/RSP-2)
Emneord [la]
Plasmodium falciparum
HSV kategori
Identifikatorer
URN: urn:nbn:se:su:diva-57253DOI: 10.1111/j.1365-3024.2010.01259.xOAI: oai:DiVA.org:su-57253DiVA, id: diva2:414865
Tilgjengelig fra: 2011-05-05 Laget: 2011-05-04 Sist oppdatert: 2018-01-12bibliografisk kontrollert
Inngår i avhandling
1. Studies on Plasmodium falciparum asexual blood stage antigens: RAP-2/RSP-2 and Pf332 in focus
Åpne denne publikasjonen i ny fane eller vindu >>Studies on Plasmodium falciparum asexual blood stage antigens: RAP-2/RSP-2 and Pf332 in focus
2011 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The life cycle of the malaria parasite is very complex and provides a number of potential targets for vaccination. In this thesis, data on two plasmodial asexual blood stage antigens (RAP-2 and Pf332) are presented.

A partial aim of the work presented herein was to investigate the mechanisms responsible for the destruction of erythroid cells in anaemia, and more specifically to define the role of the rhoptry associated protein (RAP)-2 and other members of the RAP complex, RAP-1 and -3 in processes resulting in anaemia. Antibodies to the RAP complex were shown to have the potential to mediate the destruction of RAP-2-tagged erythroid cells by phagocytosis or by complement activation and lysis. In addition, antibodies to RAP-1 and RAP-2 could induce the apoptotic death of RAP-2- tagged erythroblasts. The frequency and functionality of naturally occurring RAP-2 antibodies in the sera of anaemic and non-anaemic Cameroonian children were also investigated. All sera tested contained RAP-2-reactive antibodies by both immunofluorescence and flow cytometry. The anaemic group of children had higher levels of IgG than the non-anaemic ones, while the levels of IgM were similar. With respect to IgG subclasses, higher levels of IgG3 were seen in the non-anaemic individuals as compared to anaemic subjects. The non-anaemic individuals recognised a greater proportion of RAP-2-tagged RBCs and activated complement to a greater extent than the anaemic ones.

Earlier studies observed that humans continuously exposed to malaria, recognised Pf332 extensively. Further studies revealed that Pf332 antibodies were able to inhibit parasite growth and cytoadherence in vitro. Making use of Pf332-C231, a sub-fragment of Pf332, we studied the effects/mode of action of C231-specific antibodies on P. falciparum parasite growth and development in vitro. The antibodies appeared to act mainly on late stage parasites by two main mechanisms: 1) through the induction of abnormal/pyknotic parasites, and, 2) RBC lysis (disintegration of RBCs), thus limiting parasite growth and development. The antibody isotype in this context was IgG. Following the removal of immune pressure, parasites resumed growth, albeit at a much slower rate. The results suggest that during natural infections, antibodies to C231 could play a role in parasite control.

In summary, these data suggest that antibodies to both antigens could be instrumental in immune responses leading to disease control, but could also mediate pathology.

sted, utgiver, år, opplag, sider
Stockholm: The Wenner-Gren Institute, Stockholm University, 2011. s. 94
Emneord
immunity, malaria, RBCs, anaemia
HSV kategori
Forskningsprogram
immunologi
Identifikatorer
urn:nbn:se:su:diva-57255 (URN)978-91-7447-284-4 (ISBN)
Disputas
2011-06-14, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (engelsk)
Opponent
Veileder
Merknad
At the time of the doctoral defense, the following publication was unpublished and had a status as follows: Paper 3: Manuscript.Tilgjengelig fra: 2011-05-12 Laget: 2011-05-04 Sist oppdatert: 2018-01-12bibliografisk kontrollert

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