Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians

Abstract

Objective. To define the relative importance (RI) of class II major histocompatibility complex (MHC) alleles and peptide binding motifs as risk or protective factors for juvenile dermatomyositis (DM), and to compare these with HLA associations in adult DM.Methods. DRB1 and DQA1 typing was performed in 142 Caucasian patients with juvenile DM, and the results were compared with HLA typing data from 193 patients with adult DM and 797 race-matched controls. Random Forests classification and multiple logistic regression were used to assess the RI of the HLA associations.Results. The HLA-DRB1*0301 allele was a primary risk factor (odds ratio [OR] 3.9), while DQA1*0301 (OR 2.8), DQA1*0501 (OR 2.1), and homozygosity for DQA1*0501 (OR 3.2) were additional risk factors for juvenile DM. These risk factors were not present in patients with adult DM without defined autoantibodies. DQA1 alleles *0201 (OR 0.37), *0101 (OR 0.38), and *0102 (OR 0.51) were identified as novel protective factors for juvenile DM, the latter 2 also being protective factors in adult DM. The peptide binding motif DRB1 9 EYSTS 13 was a risk factor, and DQA1 motifs F 25 , S 26 , and 45 (V/A)W(R/K) 47 were protective. Random Forests classification analysis revealed that among the identified risk factors for juvenile DM, DRB1*0301 had a higher RI (100%) than DQA1*0301 (RI 57%), DQA1*0501 (RI 42%), or the peptide binding motifs. In a logistic regression model, DRB1*0301 and DQA1*0201 were the strongest risk and protective factors, respectively, for juvenile DM.Conclusion. DRB1*0301 is ranked higher in RI than DQA1*0501 as a risk factor for juvenile DM. DQA1*0301 is a newly identified HLA risk factor for juvenile DM, while 3 of the DQA1 alleles studied are newly identified protective factors for juvenile DM.

Juvenile idiopatiske inflammatoriske myopatier

“…Beta-hemolytiske streptokokker gruppe A (40) og coxsackievirus (41) har vaert undersøkt med negativt resultat. En studie kunne ikke påvise noen sammenheng mellom parvovirusinfeksjon og JDM (42). Ulike vaksiner har også vaert undersøkt som mulig utløsende faktor ved JDM uten at man har funnet sikre sammenhenger (33).…”

HLA class I and II alleles may influence susceptibility to adult dermatomyositis in a Mexican mestizo population

“…The principal genetic risk factor for IIM is related to chromosomal region 6p21.3 that regulates HLA [13,14].…”

Dermatomiosite juvenil: revisão e atualização em patogênese e tratamento

“…Several cases are related to the presence of class II major histocompatibility complex (MHC) (for example, HLA-DQA1*0501 -especially in Hispanics and African-Americans, and DMA*0103; DMB*0102; and DQA1*0301). 1,[2][3][4][5] Recently, DRBI*0301 was listed as the one with the greatest relative importance in JDM in Caucasians. On the other hand, the alleles DQA1*0201, *0101, and *0102 4 have been described as protective.…”

“…1,[2][3][4][5] Recently, DRBI*0301 was listed as the one with the greatest relative importance in JDM in Caucasians. On the other hand, the alleles DQA1*0201, *0101, and *0102 4 have been described as protective. There are those who defend the role of microchimerism.…”