ANTINEUTROPHIL CYTOPLASM ANTIBODIES (ANCA) OF IGA ISOTYPE IN ADULT HENOCH-SCHONLEIN PURPURA

ANCA are associated with certain forms of systemic vasculitis, and hav e been reported previously to be of the IgG and IgM isotype. We examin ed the possible association between IgA ANCA and the IgA-related disea ses Henoch-Schonlein purpura (HSP) and IgA nephropathy (IgAN). IgA and IgG ANCA were detected by isotype-specific solid-phase assays with a crude neutrophil extract, and their presence was confirmed by antigen- specific fluid-phase competitive inhibition tests and by indirect immu nofluorescence. The possible interference by IgA rheumatoid factor was excluded. IgA ANCA were detected in sera from 11/14 HSP patients (79% ), from 1/30 IgAN patients (3%), from 1/40 patients with vasculitides classically associated with IgG ANCA (2.5%), and in none of 60 sera fr om healthy blood donors. IgG ANCA were present with IgA ANCA in three patients with HSP. Only one HSP serum had anti-myeloperoxidase (MPO) a ctivity by both IgA and IgG isotype-specific ELISA, and none was posit ive for proteinase 3 (PR3). Western blot analysis performed with neutr ophil extract showed that the four strongest IgA ANCA-positive HSP ser a reacted with a 51-kD protein; Western blot performed on cellular fra ctions showed that this protein is primarily membrane-associated, and different from fibronectin. Our study suggests that adult HSP is close ly associated with circulating IgA ANCA, which may be directed against a different autoantigen than that recognized by IgG PINCA.