Are There Different Forms of Life in the Antineutrophil Cytoplasmic Antibody Universe?

The causes of most forms of noninfectious vasculitis are unknown, despite being labeled as “autoimmune.” For some autoimmune diseases, autoantibodies and their target antigens provide some information about pathogenesis and disease phenotypes. What do antineutrophil cytoplasmic antibodies (ANCAs) tell us about a patient with vasculitis? Does ANCA or the antigen that it recognizes identify patients whose vasculitis differs in clinical expression and relapse potential? If so, might this information guide treatment? Two articles in this issue (1, 2) address these questions.

Antibody directed against certain neutrophil cytoplasmic proteins (ANCA) is present in several forms of vasculitis. Wegener granulomatosis is characterized by granulomatous inflammation of the upper and lower airways, glomerulonephritis, and vasculitis of small- to medium-sized vessels. Antineutrophil cytoplasmic antibodies directed against proteinase 3 are present in about 90% of patients with severe Wegener granulomatosis and in about 65% of patients with milder disease (3). Antineutrophil cytoplasmic antibodies targeting myeloperoxidase are present in about 80% of patients with microscopic polyangiitis, another primary small- and medium-sized vessel disease that often causes glomerulonephritis and pulmonary capillaritis. These antigen specificities are not entirely reliable diagnostic tools. In about 20% of patients with Wegener granulomatosis or microscopic polyangiitis, ANCA is specific for the antigen that is usually the ANCA target in the other disease (that is, antimyeloperoxidase in Wegener granulomatosis and anti–proteinase 3 in microscopic polyangiitis) (4, 5). More important, some patients with a well-established diagnosis of Wegener granulomatosis or microscopic polyangiitis lack detectable ANCA. In the Churg–Strauss syndrome, only about 50% of patients are ANCA-positive (40% to 75%) (1, 5). Because some patients with these vasculitides do not have ANCA, how ANCA could play an essential role in pathogenesis is difficult to determine.

In this issue, Sablé-Fourtassou and colleagues (1) analyzed the clinical and histologic features of patients with the …