ANINUCLEAR ANTIBODIES IN EARLY ONSET PAUCIARTICULAR JUVENILE CHRONIC ARTHRITIS (JCA) ARE ASSOCIATED WITH HLA-DQB1^*0603: A POSSIBLE JCA-ASSOCIATED HUMAN LEUCOCYTE ANTIGEN HAPLOTIYPE

Abstract

A panel of 43 early onset pauciarticular (EOPA) juvenile chronic arthritis (JCA) patients have been typed for human leucocyte antigens (HLA) DRB1, DPB1, DQA1 alleles, and DQB1*0603 status using molecular-based methods. Increased frequencies of DRB1*08 [odds ratio (OR) 7.7, 95% confidence interval (CI) 2.6-22.3], DRB1*11 (OR 3.1, 95% CI 1.2-8.1), DRB1*1301 (OR 7.7, 95% CI 2.6-22.3), DPB1*0201 (OR 3.5, 95% CI 1.6-8.0), DQA1*0103 (OR 4.4, 95% CI 1.5-13.3), DQA1*0501 (OR 2.9, 95% CI 1.3-6.6), DQA1*0601 (OR 30, 95% CI 3.6-241) and DQB1*0603 (OR 7.3, 95% CI 3.0-17.6) were found in the EOPA-JCA group compared with Caucasoid controls. Stratification of the EOPA-JCA group into antinuclear antibody (ANA) positive (n = 18) and ANA negative (n = 25) individuals revealed that ANA positivity was only associated with DRB1*1301 (OR 4.2, 95% CI 1.0-17.3), DPB1*0201 (OR 4.0, 95% CI 1.0-15.7) and DQB1*0603 (OR 11.5, 95% CI 2.5-53.4). Further analysis of the relative contributions of HLA antigens to ANA status revealed that DQB1*0603 determined the primary HLA effect. No apparent interaction between DQB1*0603 and DRB1*1301 or between DQB1*0603 and DPB1*0201 was found to contribute to the association with ANA. We suggest that those ANA positive individuals with a restricted HLA background, (DQB1*0603 positive), defines a group of EOPA-JCA patients which will be especially valuable in the characterization of the ANA associated with EOPA-JCA.

An Insertion Mutant in DQA1*0501 Restores Susceptibility to HLA-DM: Implications for Disease Associations

“…The relationship between some of these alleles and autoimmune diseases has been reported. For example, DQ7.6 (DQA1*0601:DQB1*0301) is associated with asthma in Chinese population (43) and pauciarticular juvenile chronic arthritis without anti-nuclear antibodies (44). The allele of DQA1*0401 has been found associated with primary chronic progressive multiple sclerosis among the Ashkenazi patients (45).…”

Juvenile rheumatoid arthritis as a complex genetic trait

“…Homozygosity, at least with DR or DQ, does not result in increased risk for EOPA JRA and may even be protective (33). It should be restated that linkage disequilibrium is not involved with the susceptibility alleles discussed in this section, with the possible exception of DRB1*1301 and DPB1*0201 haplotypes (35). Fine mapping of the MHC genes in JRA, as a way of establishing the critical loci, is now possible.…”

Uveitis Related to Juvenile Idiopathic Arthritis: Familial Cases and Possible Genetic Implication in the Pathogenesis

“…Although the immunogenetic basis of JIA-associated uveitis has not been extensively investigated, a small study found that HLA DRB1*1301 allele is associated with ANA positivity, classically considered as a biomarker regarding the development of uveitis. 29 Another study has also found strong evidence supporting the involvement of HLA DRB1*13 in JIA-associated uveitis. 15 Several non-HLA susceptibility loci have been reported in association with JIA.…”