Effects of interferon-alpha on the expression of a lupus idiotype in normal humans.
Interferon (IFN) has extensive immunoregulatory effects but its role in systemic lupus erythematosus (SLE) remains obscure. The observations that a high proportion of patients with active SLE have increased IFN levels in their sera, and that IFN injected to lupus-prone mice aggrevates their disease, led us to examine the effects of IFN on the production of 16/6--a high frequency idiotype of monoclonal anti-DNA antibodies produced by human-human hybridomas derived from SLE patients. Peripheral blood mononuclear cells (PBMC) of healthy donors or of patients with SLE were incubated with IFN and pokeweed mitogen (PWM). Seven-day supernatants were assayed for total IgM, for IgM with 16/6 idiotype, and for IgM anti-DNA activity. PWM-stimulated PBMC of all healthy donors examined produced the 16/6 idiotype (mean 2.5 ng/ml). A significant increase of 16/6 in normals (above the level with PWM alone) was noted with 10-100 u/ml of IFN-alpha but not with 500 u/ml. In 3/10 normals the addition of IFN-alpha resulted in detectable anti-DNA activity. The IFN-induced increase in 16/6 idiotype was significantly more than the increase in IgM (335% vs 47% above baseline, with 10 u/ml of IFN). These effects of IFN could not be demonstrated in the absence of PWM nor in T-cell-depleted preparations. Recombinant IFN-gamma had no augmenting effect on 16/6 production. Three SLE patients in remission had elevated levels of 16/6 in their PBMC supernatant (15-200 ng/ml) which could not be further augmented by IFN. Thus, we have demonstrated the potential of PWM-stimulated normal lymphocytes to generate a "lupus" idiotype and shown that production of this idiotype requires T cells and is preferentially enhanced by IFN-alpha. Further studies of the effects of IFN on the expression of anti-DNA antibodies may clarify a postulated role of IFN in autoimmune diseases.
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000209:etiology; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007370:Interferon Type I / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008214:Lymphocytes / Q000378:metabolism; D008875:Middle Aged; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011817:Rabbits
D001323:Autoantibodies; D007106:Immune Sera; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007370:Interferon Type I; D011043:Pokeweed Mitogens; D004247:DNA