Stratification of the haplotype data suggested that susceptibility to JIA in the haplotype spanning the SLC11A1 locus is independent (P < 0.01) of an association with a DRB1 JIA shared epitope (DRB1*JIASE) that includes well-characterized strong susceptibility to DRB1*08 and *11 alleles.
We found DRB1*0801/DQB1*0402 haplotype to be strongly associated (p < 0.001) with JIA, supporting findings of the haplotype associations-based ASP design.
These findings are consistent with the most compelling results of previous reports on HLA associations and suggest a JIADRB1 shared epitope encompassing critical amino-acid residues in the third hypervariable region of this molecule.
Three haplotypes (DRB1*08-DQA1*0401-DQB1*0402; DRB1*11-DQA1*05-DQB1*03; DRB1*1301-DQA1*01-DQB1*06) were associated with increased risk and one (DRB1*04-DQA1*03-DQB1*03) with decreased risk of JIA.
No haplotypes which carried DQA1*0401 and DQB1*0402 in the absence of DRB1*08 were found, either among patients with JIA (Polish and Norwegian) or among the controls (Polish).
JIA is associated with particular alleles at, at least, three different HLA loci: HLA-A (HLA-A*0201), -DR/DQ (DRB1*08, DRB1*11, DRB1*13) and -DP (DPB1*0201, DPB1*0301), with marked differences between the disease subtypes.
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).
Certain HLA associations (DRB1*0801, DPB1*0201) appear to be present in patients with JA in most studies; others (DRB1*1301, DPB1*0301) are more variable.