HLA–D region epitopes associated with juvenile arthritis. recognition by alloreactive t cell clones and alloantisera

Abstract

The HLA-D region antigens DR5 (wll,w12), DRw6 (w13,w14), DRw8, DRw52, and DQwl have previously been shown to be increased in frequency in subsets of patients with juvenile arthritis. Since the HLA-D region is complex (composed of at least 3 subregions encoding multiple molecules, each in turn presenting multiple alloantigenic epitopes), we sought to clarify whether one strongly associated factor might explain the previous findings. To search for the pertinent HLA-D region stimulatory epitopes, alloreactive T cells were primed against DR5 and DRw6 haplotypes and cloned by limiting dilution. Three T cell clones and I alloantiserum met the criteria for significant association with juvenile arthritis on patient testing, including DR5, DRw6, and DRw8 haplotypes. Monoclonal antibody blocking revealed that all 4 recognized epitopes on DR subregion products. For 2 of the clones, the relative risks for JA (10.5 and 9.4) were higher than the risks with any other previously described typing reagents.

Hla antigens in juvenile Arthritis

“…We observed this sequence in 19 patients in the present study. Previous studies had suggested that similar immunogenetic factors were involved in susceptibility to both the pauciarticular and the polyarticular RF-negative forms of JA (12). In the present study, HLA-DRw8-Dw8.1 and DQw4 were increased in all 3 groups of JA patients studied compared with the frequencies found in normal controls.…”

“…Studies with T cell clones having such reactivity patterns confirmed this possibility (12,16). A separate effect of DPw2, primarily involved in susceptibility for pauciarticular disease, has been postulated (14,15).…”

“…Children with rheumatoid factor (RF)-positive polyarthritis, those with systemic onset, and boys with late onset of arthritis have usually been the subject of separate studies and will not be considered further in this report. The RF-negative pauciarticular and polyarticular groups were sometimes combined because it was thought the HLA antigens involved in disease susceptibility in these 2 groups of patients were similar (12). The HLA antigens identified as conferring risk for JA in various reports were DRw8 (1,(4)(5)(6)(8)(9)(10)(11), DR5 (2,3,6-9,13), DRw6 (7), DRw52 (8,9,13), DQwl (lo), and more recently, DPw2 (14,15).…”

Wilson's disease presenting as isolated arthritis of the hip

“…It is characterized by degenerative changes of the central nervous system, cirrhosis of the liver, and renal dysfunction (1,2). In the natural course of the disease, osteoarticular changes have been observed (3)(4)(5)(6)(7)(8).…”

6.2-05 Rheumatoid-factor-negative polyarticular and pauciarticular juvenile arthritis are immunogenetically distinct

“…One hypothesis proposed to explain the involvement of so many different HLA antigens suggested that a form of DRw52, which might include DR5, DRw6, and DRw8, but excludes DR3, was the main susceptibility factor. Studies with T cell clones having such reactivity patterns confirmed this possibility (12,16). A separate effect of DPw2, primarily involved in susceptibility for pauciarticular disease, has been postulated (14,15).…”