title: Genetic evidence for involvement of adaptive immunity in the development of IgA nephropathy: MHC class II alleles are protective in a Caucasian population.
abstract: There is evidence suggesting that IgA nephropathy (IgAN) is an immunological disease. The role of HLA class II DR beta 1 (DRB1) has previously not been well studied. The aim of our study was to investigate the association of HLA-DRB1 variants with IgAN in a Swedish Caucasian cohort. Our study consisted of 213 patients with biopsy proven IgAN, all of self-reported Caucasian ancestry. As a control cohort, 1569 healthy subjects from the same population in Sweden were included. HLA-DRB1 low-resolution genotyping was performed and odds ratios were calculated to assess the risk. In an allelic model the HLA-DRB1(*)03 and (*)10, demonstrated association for IgAN after correction for multiple comparison, with subsequent OR=0.54 (95% CI 0.37-0.78) and 3.44 (95% CI 1.67-7.07). When the influence of risk allelic groups was adjusted for protective allelic groups and vice versa, only a protective effect of HLA-DRB1(*)03 remained significant. In conclusion, the variants of HLA-DRB1 were associated with IgAN of which the HLA-DRB1(*)03 revealed a strong protective effect for IgAN. Our data replicates finding from other Caucasian populations and suggest that involvement of adaptive immunity may be of importance in the development of the disease.
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mai Tuyet
authors.initials: MT
authors.lastname: Vuong
authors.forename: Sigrid
authors.initials: S
authors.lastname: Lundberg
authors.forename: Iva
authors.initials: I
authors.lastname: Gunnarsson
authors.forename: Lars
authors.initials: L
authors.lastname: Wramner
authors.forename: Emeli
authors.initials: E
authors.lastname: Lundström
authors.forename: Anders
authors.initials: A
authors.lastname: Fernström
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Jacobson
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology*; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II