FC gamma RII (CD32)-dependent induction of interferon-alpha by serum from patients with lupus erythematosus

Interferon-alpha (IFN-alpha) is detected in the serum of 70-80% of patients with systemic lupus erythematosus (SLE). Furthermore, soluble factors in S LE serum can induce peripheral blood mononuclear cells (PBMC) to produce IF N-alpha. The purpose of this work was to investigate the mechanism of this IFN-alpha induction. In eleven of fifteen SLE serum samples, an IFN-alpha i nducing activity was detected, whereas serum from healthy controls, patient s with other autoimmune disease and patients,vith viral infections were ine ffective under the same conditions. After gel filtration of the serum, the inducing activity was found in the same fraction as IgG. The IFN-alpha indu cing activity was inhibited by native monoclonal antibodies to the receptor s for the Fc portion of IgG: Fc gamma RIIA/C and Fc gamma RIIB subclasses ( CD32) and by their F(ab)'(2) fragments. Purified Fc fragments of human IgG were also effective in abolishing the IFN-alpha-inducing activity. Since no anti-CD32 autoantibodies were found in SLE serum, this IFN-alpha-inducing activity may be due to immune complex antibodies. Such results may allow be tter understand the origin of endogenous IFN-alpha, which has a deleterious effect on the course of this autoimmune disease. The inhibition of this fu nction by the CD32 antibody could lead to new therapeutic approach in SLE.