HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis

Abstract

The HLA genetic region was studied in 51 patients with systemic onset juvenile rheumatoid arthritis: 35 with childhood onset and 16 with adult onset (adult Still's disease). HLA genotypes were established by including family members, 261 of whom were also typed in the study. The most marked difference between patients and controls involved the HLA-DR4 gene, which occurred with a frequency of 0.348 in the childhood onset patients and 0.170 in the controls (x2 = 8.97, P = 0.0028, adjusted P = 0.017). In contrast, the adult onset patients showed a marginal increase in HLA-DR7, but were similar to controls with respect to HLA-DR4. HLA-Bw35 was increased in children with systemic onset disease, in accordance with earlier findings. The results suggest that patients with systemic onset juvenile rheumatoid arthritis have complex HLA associations which are different in childhood onset and adult onset disease.

HLA-DRB1*11and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

“…This relationship has been examined in children from a variety of ancestral backgrounds. Many alleles of HLA-DRβ1, including HLA-DRB1*11 (16), have been reported to affect sJIA risk in studies of single populations (11)(12)(13)(14)(15)(16). However no association has reached the level of genome-wide significance and no single HLA-DRB1 allele has been found to influence sJIA risk across studies or populations (9,17), leading some to conclude that class II HLA molecules are not risk factors for sJIA (18).…”

“…As a result, most genetic studies of sJIA have examined modestly sized collections. The most intensively studied genetic locus in sJIA has been the cluster of HLA molecules within the MHC locus (11)(12)(13)(14)(15)(16). HLA molecules are a critical component of the adaptive immune system, acting to present peptide antigens to antigen receptors on T lymphocytes.…”

“…HLA molecules are a critical component of the adaptive immune system, acting to present peptide antigens to antigen receptors on T lymphocytes. Studies of classic HLA locus-types in sJIA have often reported one or more sJIA-associated alleles (11)(12)(13)(14)(15)(16), frequently at class II HLA loci, although no association has met the contemporary standard of genome-wide significance. In fact, there has been little agreement and no consensus among these studies, adding uncertainty to the proposed relationship between sJIA and the MHC locus.…”

Adult‐onset still's disease. Disease course and HLA associations

“…Moreover, Bw35 was decreased in the total group. Recently, Miller et a1 (6) observed an increased gene frequency of DR4 in 35 patients with juvenile-onset Still's disease, but not in 16 patients with adult-onset disease. Until now, a negative association with DRl and Bw35 has never been reported in patients with juvenile-or adult-onset Still's disease.…”

“…In adults, an increased frequency of B14 (6), Bw35 (9), Cw4 (9), and DR7 (6) has been found. This study reports on HLA phenotypes in 42 patients with AOSD, and includes radiologic features and disease course.…”