The value of serial ANCA testing during follow-up studies in patients with ANCA-associated vasculitides. A review

Anti-neutrophil cytoplasmic autoantibodies (ANCA) have specificity for cytoplasmic proteins of myeloid cells. Many antigens recognized by ANCA have already been described. In most patients with primary forms of vasculitis such as Wegener's granulomatosis (WG), the Churg-Strauss Syndrome (CSS) and microscopic polyangiitis (MPA), ANCA with specificity for either proteinase 3 (PR3) or myeloperoxidase (MPO) can be detected. The diagnostic potential of these antibodies is now fairly well established. In a patient with signs and symptoms of vasculitis, anti-PR3 suggests a diagnosis of WG, whereas anti-MPO is associated with WG, CSS, MPA, and with idiopathic necrotizing crescentic glomerulonephritis. Anti-MPO, however, also occurs, incidentally, in other diseases. During follow-up studies, it has been shown that the persistence of ANCA or its reappearance is a risk factor for relaspe and/or poor renal outcome. In addition, rising ANCA levels are associated with recurrence in many cases. ANCA increases are, however, not invariably followed by relapse and high levels of ANCA may be found during clinical remission. So, different functional characteristics of antibodies may be of importance with respect to the development of relapses. Functional characteristics that might be important in disease reactivation include: subclass distribution, the capacity of ANCA to induce oxygen radicals, its capacity to inhibit the irreversible inactivation of proteinase 3 by al-antitrypsin, and/or its capacity to inhibit the proteolytic activity of PR3. ANCA levels may be either used to institute ''pre-emptive'' therapy, or to closely monitor patients to detect early signs of disease relapse, or to adopt an approach in which reductions of immunosuppressive treatment are postponed in those patients who remain ANCA positive. In a prospective study, relapses were prevented when treatment was started immediately after an increase in ANCA titers. These data, however, must be confirmed by studies on larger groups of patients. Hence, there is still an obvious need for more prospective studies