Autoantibodies to native myeloperoxidase in patients with pulmonary hemorrhage and acute renal failure

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Abstract
Sera from 245 patients were screened by indirect immunofluorescence for perinuclear/nuclear staining (P-ANCA) of ethanol-fixed neutrophils, a staining pattern which is associated with the presence of antibodies to myeloperoxidase. Using immunoblot and immunoprecipitation techniques on 15 P-ANCA-positive sera, 13 patients demonstrated antibody to purified or native myeloperoxidase but not to denatured myeloperoxidase. In patients with P-ANCA, the most frequent reason for medical attention was hemoptysis (8/13; 62%). Of the 15 sera with P-ANCA, acute renal failure was identified in 9 patients (60%). Five patients (33%) had both. All patients (eight of eight) with hemoptysis had antibodies which bound functional MPO as compared to three of seven P-ANCA-positive patients without hemoptysis (P<0.001), suggesting that antibodies which recognize conformational sites on native myeloperoxidase occur in a subgroup of patients with alveolar hemorrhage as their presenting clinical sign. These findings may provide insight into the disease process associated with P-ANCA. We further identify a subgroup of patients with a severe pulmonorenal syndrome and antibodies recognizing native myeloperoxidase.