Association of neutropenia in systemic lupus erythematosus (SLE) with anti-Ro and binding of an immunologically cross-reactive neutrophil membrane antigen

SLE is associated with the production of autoantibodies to self-constituent s. In particular, certain ribonucleoprotein particles are targeted. Despite the multitude of autoantibodies produced and the remarkable concentrations of these antibodies in the sera of SLE patients, there have been little da ta that the autoantibodies found in SLE are involved in the pathogenesis of disease or its manifestations. The present work demonstrates that anti-Ro (or SSA) is associated with granulocytopenia, binds the surface of granuloc ytes and fixes complement to this membrane surface. Binding is a property o f anti-Ro Fab fragments and can be inhibited by 60-kD Ro. However, the anti gen bound on the surface of granulocytes is a 64 000 mol. wt protein that i s a novel autoantigen in SLE. As suggested by inhibition studies, sequence identity between 60-kD Ro and eight tandem repeats in the 64-kD antigen may be responsible for the observed serologic cross-reactivity. These data imp ly that anti-Ro antibodies that also bind the 64-kD protein mediate neutrop enia in patients with SLE.