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The dog as a genetic model for immunoglobulin A (IgA) deficiency: Identification of several breeds with low serum IgA concentrations
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
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2014 (Engelska)Ingår i: Veterinary Immunology and Immunopathology, ISSN 0165-2427, E-ISSN 1873-2534, Vol. 60, nr 3-4, s. 255-259Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Immunoglobulin A (IgA) serves as the basis of the secretory immune system by protecting the lining of mucosal sites from pathogens. In both humans and dogs, IgA deficiency (IgAD) is associated with recurrent infections of mucosal sites and immune-mediated diseases. Low concentrations of serum IgA have previously been reported to occur in a number of dog breeds but no generally accepted cut-off value has been established for canine IgAD. The current study represents the largest screening to date of IgA in dogs in terms of both number of dogs (n = 1267) and number of breeds studied (n = 22). Serum IgA concentrations were quantified by using capture ELISA and were found to vary widely between breeds. We also found IgA to be positively correlated with age (p < 0.0001). Apart from the two breeds previously reported as predisposed to low IgA (Shar-Pei and German shepherd), we identified six additional breeds in which > 10% of all tested dogs had very low (<0.07 g/l) IgA concentrations (Hovawart, Norwegian elkhound, Nova Scotia duck tolling retriever, Bullterrier, Golden retriever and Labrador retriever). In addition, we discovered low IgA concentrations to be significantly associated with canine atopic dermatitis (CAD, p < 0.0001) and pancreatic acinar atrophy (PAA, p = 0.04) in German shepherds.

Ort, förlag, år, upplaga, sidor
2014. Vol. 60, nr 3-4, s. 255-259
Nyckelord [en]
Immunoglobulin A (IgA) deficiency, Immunodeficiency, Dog, German shepherd
Nationell ämneskategori
Immunologi inom det medicinska området Veterinärmedicin
Identifikatorer
URN: urn:nbn:se:uu:diva-230943DOI: 10.1016/j.vetimm.2014.05.010ISI: 000340221400014OAI: oai:DiVA.org:uu-230943DiVA, id: diva2:743252
Tillgänglig från: 2014-09-03 Skapad: 2014-09-01 Senast uppdaterad: 2018-01-11Bibliografiskt granskad
Ingår i avhandling
1. Genetic Studies in Dogs Implicate Novel Genes Involved in Atopic Dermatitis and IgA Deficiency
Öppna denna publikation i ny flik eller fönster >>Genetic Studies in Dogs Implicate Novel Genes Involved in Atopic Dermatitis and IgA Deficiency
2015 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

This thesis presents genetic studies of atopic dermatitis (AD) and IgA deficiency in dogs.

AD is a chronic inflammatory and pruritic skin disorder caused by allergic reactions against environmental allergens. Both genetic and environmental factors are involved in the development of Canine AD (CAD) and human AD. In Paper I, we performed genome-wide association studies (GWAS) and identified a locus on chromosome 27 significantly associated with CAD in German shepherd dogs (GSDs). The locus contains several genes and fine-mapping indicated strongest association close to the candidate gene PKP2. In Paper II, we performed additional fine-mapping and identified four highly associated SNPs located in regions with transcriptional regulatory potential in epithelial and immune cells. The risk alleles were associated with increased transcriptional activity and the effect on expression was cell-type dependent. These data indicate that multiple cell-type specific enhancers regulate the expression of PKP2, and/or the neighboring genes YARS2, DNM1L and FGD4, and predispose GSDs to CAD.

IgA deficiency is the most common primary immune deficiency disorder in both humans and dogs, characterized by a higher risk of recurrent mucosal tract infections, allergic and other immune-mediated diseases. In Paper III, we performed the widest screening (to date) of serum IgA levels in dog breeds (Ndogs=1267, Nbreeds=22) and defined eight breeds as predisposed to low IgA levels. In Paper IV, we performed GWAS in four of the breeds defined as prone to low IgA levels. We used a novel percentile groups-approach to establish breed-specific cut-offs to perform analyses in a close to continuous manner. In total, 35 genomic loci were suggestively associated (p<0.0005) to IgA levels, and three genomic regions (including the genes KIRREL3 and SERPINA9) were genome-wide significantly associated with IgA levels in GSDs. A ~20kb long haplotype on chromosome 28, significantly associated to IgA levels in Shar-Pei dogs, was positioned within the first intron of the gene SLIT1 overlapping with a possible dog domestication sweep.

This thesis suggests novel candidate genes involved in two immune-mediated disorders in the dog. Hopefully, these results will become an important resource for the genetic research of the corresponding human diseases.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2015. s. 88
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1128
Nyckelord
GWAS, canine model, genetic association, immunogenetics, atopic dermatitis, IgA deficiency
Nationell ämneskategori
Medicinsk genetik
Forskningsämne
Molekylär genetik
Identifikatorer
urn:nbn:se:uu:diva-259606 (URN)978-91-554-9304-2 (ISBN)
Disputation
2015-10-06, B22, BMC, Husargatan 3, Uppsala, 13:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2015-09-11 Skapad: 2015-08-10 Senast uppdaterad: 2018-01-11

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Av författaren/redaktören
Tengvall, KatarinaFall, ToveIvansson, EmmaLindblad-Toh, Kerstin
Av organisationen
Institutionen för medicinsk biokemi och mikrobiologiScience for Life Laboratory, SciLifeLabMolekylär epidemiologi
I samma tidskrift
Veterinary Immunology and Immunopathology
Immunologi inom det medicinska områdetVeterinärmedicin

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