Immunoregulatory aberrations in patients with polyarticular juvenile rheumatoid arthritis

The presence of hypergammaglobulinemia and various circulating autoantibodies in children with polyarticular juvenile rheumatoid arthritis (JRA) implies an immunoregulatory disorder. We report here experiments planned to elucidate the underlying cellular aberrations in this disease. Twelve children with polyarticular JRA were studied. Percentages of Leu-1, Leu-2, and Leu 3 T cells were comparable to those of normal individuals. Immunofluorescent double staining studies demonstrated elevated numbers of activated (DR+) T cells of both Leu-2 and Leu-3 phenotype. B cells characterized both phenotypically (Leu-12) and functionally (as spontaneous plaque-forming cells, PFC) were elevated. In vitro PFC responses to pokeweed mitogen (PWM) and Epstein-Barr virus (EBV) were diminished. The levels of concanavalin A-induced suppressor cells of the PWM-stimulated PFC responses were comparable to control values. In contrast, the EBV-associated suppressor T cells were significantly impaired in both EBV-seropositive and EBV-seronegative patients. These studies indicate that peripheral blood B-cell activity is abnormal in polyarticular JRA. Defective T-cell responses in vitro suggest that this may be due to disruption of normal regulatory circuits between B and T cells and may contribute to the pathogenesis of this disease.