HDCN Article Review/Hyperlink

Merkel PA, Polisson RP, Chang YX, Skates SJ, Niles JL

Prevalence of antineutrophil cytoplasmic antibodies in a large inception cohort of patients with connective tissue diseases

Ann Int Med (Jun) 126:866-873 1997

Antineutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (C-ANCA) and myeloperoxidase (P-ANCA) are hallmarks of vasculitis, and can also be seen in idiopathic necrotizing and crescentic GN. When assayed by indirect immunofluorescence, anti-PR3 ANCA produces a cytoplasmic pattern of staining, whereas anti-MPO produce a perinuclear pattern, which is largely an artifact of fixation. The question of falsely positive ANCA tests is a vexing one, as renal involvement with a positive ANCA test, if indicative of vasculitis, often militates for aggressive treatment with cytotoxic drugs.

In this paper, the question of the prevalence of falsely positive ANCA tests (e.g., not associated with vasculitis) in patients with connective tissue disease is explored. Stored serum specimens from a study that was designed to study the course of undifferentiated connective tissue disease, but which included substantial numbers of patients with SLE, scleroderma, Sjogren syndrome, and the antiphospholipid syndrome. Random blood donors served as a negative control group, and fifty-two patients with Wegener s granulomatosis, microscopic polyangiitis, or related vasculitis served as positive controls. ANCA was assayed by both indirect immunofluorescence and by two ELISA methods (a direct and a sandwich technique) specific for anti-MPO or anti-PR3.

ANCA-C was relatively specific, as it was not present in any of the patients without vasculitis but with rheumatoid arthritis, lupus, scleroderma, or polymyositis. Nor was it present in patients with Sjogren's syndrome or anti-phospholipid antibody syndrome. P- ANCA, however, was not nearly as specific, as it occurred frequently (31%) in patients with SLE. Atypical ANCA fluorescence, which could not be typed specifically as cytoplasmic or perinuclear, was present in 10-20% of various connective tissue disorders excluding SLE, and in 39% of SLE patients! Almost none of the patients positive for P- ANCA by indirect immunofluorescence were positive for anti-MPO antibodies by ELISA.

Comment: This is an elegantly done study. The patient sample size is large, a wide spectrum of connective tissue diseases are represented, and follow-up of the patients was long to make sure that they did not develop signs or symptoms of vasculitis over a period as long as 5 years. Furthermore, all samples were assayed in a blinded fashion. The clinical message from this study is, that indirect immunofluorescence tests for ANCA should not be used to diagnose nor treat patients with vasculitis, but that more specific anti-PR3 and anti-MPO ELISA tests should be employed. (John T. Daugirdas, M.D., University of Illinois at Chicago)