Evidence for IgA-specific B cell hyperactivity in patients with IgA nephropathy.

Spontaneous in vitro IgA synthesis by peripheral blood mononuclear cells (PBMC) of patients with IgA nephropathy was elevated; 419 +/- 71 ng/10(6) cells (Mean +/- SEM) compared with controls; 217 +/- 35 (P less than 0.02). Pokeweed mitogen (PWM) stimulated IgA synthesis was also elevated in patients; 4326 +/- 1140 ng/10(6) cells (Mean +/- SEM) versus 1458 +/- 406 (P less than 0.02) but the PWM stimulation index for patients did not differ significantly from that of the controls. Concanavalin A (Con A) suppression of PWM stimulated IgA synthesis resulted in the generation of similar quantities of IgA by PBMC from both patients and controls but the percentage suppression was significantly elevated in patients; 87 +/- 5 (Mean +/- SEM) versus 58 +/- 10 (P less than 0.05). Synthesis of IgG and IgM followed the same pattern as that described for IgA. T and B cells from patients and controls were cultured alone and in various co-culture permutations. Enriched B cells of patients demonstrated a selectively increased capacity for IgA production; 266 +/- 106 ng/5 X 10(5) cells (Mean +/- SEM) compared with controls; 42 +/- 9 (P less than 0.01) and this parameter correlated significantly with serum IgA concentrations (R = 0.77, P less than 0.05). Overall analysis of co-culture data showed no significant difference between the influences of autologous, control or patient T cells on immunoglobulin synthesis by normal B cells. Autolymphocytotoxic antibodies were not detected and, compared with controls, patient sera had no differential effect on numbers of IgA producing cells generated in culture.(ABSTRACT TRUNCATED AT 250 WORDS)