Similar disturbances in B cell activity and regulatory T cell function in Henoch-Schönlein purpura and systemic lupus erythematosus.

Abstract

Abstract The immunoglobulin synthesizing activities of peripheral mononuclear cells (MNC) from five patients with Henoch-Schönlein purpura (HSP) and eight patients with active systemic lupus erythematosus (SLE) were compared. Cumulative amounts of IgM, IgG, and IgA synthesized and secreted by unstimulated and PWM-stimulated patient cells over a 12-day period were determined in a solid-phase radioimmunoassay. In unstimulated control cultures mean rates of IgM, IgG, and IgA synthesis were less than 250 ng/ml. The synthetic activities of patient MNC were markedly increased. In HSP cultures IgA was the major immunoglobulin class produced (2810 1.33 ng/ml) followed by IgG (1754 1.32 ng/ml) and IgM (404 1.16 ng/ml). In SLE cultures IgA and IgG syntheses were equally elevated (4427 1.20 and 4438 1.49 ng/ml, respectively) whereas IgM synthesis averaged 967 1.66 ng/ml. PWM stimulation of patient MNC caused a sharp decline in the synthesis of all three immunoglobulin classes. After T cell depletion B cell-enriched fractions from HSP and SLE patients maintained high levels of IgA and IgG synthesis that were inhibited by PWM and by normal allogeneic but not autologous T cells. In PWM-stimulated co-cultures, patient T cells non-specifically suppressed the synthetic activities of autologous and control B cells. In contrast patient B cells achieved normal levels of immunoglobulin synthesis when cultured with control T cells plus PWM. In longitudinal studies patient B and T cell disturbances persisted despite clinical improvement. These findings indicate that sustained B cell activation is not specific for SLE. Moreover, the simultaneous occurrence of similar B and T cell abnormalities in HSP and SLE suggests the cellular changes are closely interrelated and may represent an integrated response to a variety of immunologic stimuli.