Autoantibodies to crude human leucocyte interferon (IFN), native human IFN, recombinant human IFN-alpha 2b and human IFN-gamma in healthy blood donors.

Recently, naturally occurring antibodies to IFN-alpha were discovered in a few systemic lupus erythematosus (SLE) and cancer patients; however, in most patients monitored for anti-IFN antibodies before treatment, no antibodies were found. In an attempt to explain the 'IFN-blocking effect' that we observed in all serum samples we investigated 200 sera from healthy blood donors. We isolated the globulin fraction, and used rabbit anti-human IgG and IgM columns, protein A columns and T-gel affinity chromatography to isolate human IgG and IgM. All sample fractions were tested in a biological IFN neutralization assay by means of a sensitive MTT-assay. We found that normal human serum contained autoantibodies to crude human leucocyte IFN, native human fibroblast IFN, recombinant human leucocyte IFN-alpha 2b and recombinant human IFN-gamma, and that these naturally occurring antibodies were biologically active immunoglobulins of IgG and IgM type. These anti-IFN antibodies were also present in purified human normal immunoglobulin pools. We conclude that all humans have naturally occurring anti-interferon antibodies in their serum, and it is a tempting theory that human cytokines and lymphokines are, at least partly, regulated by immunoglobulins.