Spontaneously occurring neutralizing antibodies against granulocyte-macrophage colony-stimulating factor in patients with autoimmune disease

There is increasing evidence that spontaneous anticytokine autoantibodies a re associated with chronic infections and autoimmune diseases. We report th e sporadic occurrence in autoimmune diseases of such autoantibodies to gran ulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine involved in inflammation and the regulation of proliferation, differentiation and fu nction of granulocytic and monocytic cell lineages. In 41 of 425 patients t ested, we found low to moderate levels of autoantibodies binding to GM-CSF in serum or plasma. These were most prevalent in patients with myasthenia g ravis (MG). However, neutralizing autoantibodies against CM-CSF were very r are, being found in only three patients. Two had autoimmune MG, one with th ymoma (Patient A) and the other (Patient B) with 'seronegative' MG, i.e. wi thout the antiacetylcholine receptor autoantibodies characteristic of most MG patients, and a third (Patient D) had multiple sclerosis. Only very limi ted amounts of Patient A and Patient D serum/plasma were available for anal ysis and therefore further studies were carried out on the more plentiful s amples from Patient B. The anti-GM-CSF autoantibodies of Patient B were pre dominantly polyclonal immunoglobulin G and strongly neutralized recombinant human (rh) GM-CSF derived from different expression systems. They had simi lar immunological and immunochemical characteristics to anti-GM-CSF antibod ies that developed in immunocompetent colorectal carcinoma patients followi ng (rh)GM-GSF therapy. In serial samples from Patient B, the anti-GM-CSF au toantibodies were undetectable from diagnosis at age 8 years until at least age 13, but then developed spontaneously during (temporary) withdrawal of immunosuppressive treatment. Their neutralizing activity has persisted sinc e their first detection at age 15 years 1 month, and was at its highest lev el recently at age 17 years 7 months. There was no obvious association with other autoimmune phenomena, nor were any haematological deficiencies overt ly manifested, suggesting that any loss of GM-CSF function may have been co mpensated for by other cytokines.