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 .mu./ml of IFN-.alpha. but not with 500 .mu./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 .mu./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.