A B S T R A C T Evidence has been sought for a genetically determined predisposition among children with juvenile rheumatoid arthritis (JRA) who are also at particular risk for the development of inflammatory eye disease.45 unrelated Caucasian patients (41 female) with early-onset pauciarticular JRA were human leukocyte antigen (HLA) typed. 28 of the study group were found to be HLA-DRw5 compared with 16 of 84 controls (X2, 24.3, P = <0.001). 9 patients were HLA-DRw8 compared with 4 of 84 controls (X2, 7.51, P = <0.01). Iritis developed in 24 of the 45 children studied, 17 of whom were typed as HLA-DRw5 when compared to controls (X2, 26.76, P = <0.001) and 6 with iritis typed as HLA-DRw8 (X2, 9.10, P = <0.01). Antinuclear antibody was found in the serum of 17 of the 28 patients typing as HLA-DRw5 compared with 4 of the 17 who did not have this antigen (X2, 5.88, P = <0.02). No such association was seen in patients with HLA-DRw8.In a study of linked genes, a delta value of 0.090 was found for HLA-DRw5 with HLA-B12, of 0.070 for DRw5 with HLA-Cw4, and a value of 0.050 for DRw5 and HLA-Bw35. This suggests a linkage disequilibrium between HLA-DRw5 and these two B series alleles, a conclusion which was supported by haplotype analysis in families of 11 of the disease probands. HLA-DRw5 has not previously been reported to be increased in any rheumatic disease group. It is proposed that HLA-DRw5 is a genetic marker defining those at risk for early-onset pauciarticular JRA with iritis.

Two genetic markers, HLA‐Bw35 and HLA‐B8, are found to be associated with “febrile” or “systemic” onset juvenile rheumatoid arthritis (JRA). Evidence is presented that JRA patients are probably heterogeneous with respect to these antigens.

Systemic lupus erythematosus (SLE) is characterized by increased numbers of circulating B cells activated polyclonally to secrete immunoglobulin. Because T cells secrete, or shed, various factors that are functionally important in regulating immunoglobulin production by B cells, a reverse hemolytic plaque assay was developed to quantitate such activated T cells. In this technique, we used a rabbit antiserum raised to supernatants of concanavalin-A-stimulated human lymphocytes. The relevant antigenic specificity of this antiserum is directed toward the shed surface membrane determinant(s) preferentially expressed on activated T cells. Freshly isolated peripheral blood mononuclear cells from 14 SLE patients contained more than 10 times the number of endogenously activated T cells than cells from normal subjects. Within the SLE group, plaqueforming T cells were particularly increased in patients with active disease. By linear regression analysis, a significant positive correlation was revealed between such activated T cells and immunoglobulin-secreting B cells, also measured by a reverse plaque assay (r = circulate in increased numbers in SLE. Additional investigation will be required to define the molecular nature of the T cell product(s) being measured and to clarify the relationship of these findings to the immunoregulatory abnormalities in this disorder. 0.83). It appears that both activated B cells and T cellsPresent investigations of the immunologic abnormalities in systemic lupus erythematosus (SLE) focus on humoral hyperactivity and T cell hypofunction. The hypergammaglobulinemia, autoantibody formation, and elevated antibody titers to exogenous antigens that characterize this disorder are accompanied by increased numbers of circulating B cells endogenously activated to secrete immunoglobulin (1-5) or specific antibodies (6-8). Most investigators have found T cell function to be impaired with respect to mitogen, antigen, or allogeneic lymphocyte responsiveness (9-12); generation of T suppressor cell activity (13-16); and autologous mixed lymphocyte reactivity (17). In general, both T and B cell abnormalities have been most marked in patients who have active SLE.Available technology has limited the assessment of ongoing T cell activation in SLE; however, increased numbers of small lymphocytes that synthesize DNA have been detected in SLE by autoradiographic techniques (18,19). We have developed a reverse hemolvticL daaue a s p L Ibased _nn--tbe-approach originally used in murine systems by Primi et a1 (20)] that quantitates activated T cells, both in mononuclear cell preparations from freshly isolated peripheral blood and after in vitro culture in the presence of various mitogens and antigens (21). In the present study, this method has been applied to the analysis of circulating T cells in SLE. From the data, it appears

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