A novel specificity of anticytoplasmic autoantibodies directed against eosinophil peroxidase

Abstract

SUMMARY Vasculitis associated anticytoplasmic autoantibodies (ANCA) are directed against enzymes in the granules of both neutrophils and monocytes. These autoantibodies can be detected by indirect immunofluorescence technique (IIFT) using ethanol-fixed cytospins. We here report the identification of a novel specificity of autoantibodies, present in the sera of eight patients, that reacted only with eosinophils in the IIFT. By immunoprecipitation and ELISA experiments it was shown that the autoantibodies in these sera were directed against eosinophil peroxidase (EPO). There was no apparent influence on initial substrate conversion rate, but reduced plateau levels suggested increased inactivation of the enzyme in the course of the peroxidase reaction. Flow cytometry studies demonstrated the presence of EPO on the surface of primed eosinophils. Anti-EPO sera and purified anti-EPO immunoglobulins significantly increased the release of reactive oxygen species from primed eosinophils. The patients with anti-EPO antibodies suffered from clinically diverse disorders, with more or less generalized manifestations involving the kidneys, blood vessels, lungs and/or joints.