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  • Title: Relationship between disease activity and anti-neutrophil cytoplasmic antibody concentration in long-term management of systemic vasculitis.
    Author: De'Oliviera J, Gaskin G, Dash A, Rees AJ, Pusey CD.
    Journal: Am J Kidney Dis; 1995 Mar; 25(3):380-9. PubMed ID: 7872315.
    Abstract:
    Autoantibodies directed against neutrophil cytoplasmic antigens (ANCA) are valuable in the diagnosis of primary systemic vasculitis, and immunofluorescence studies suggest that changes in ANCA concentration reflect changes in disease activity. We used enzyme-linked immunosorbent assays to examine retrospectively the relationship between ANCA concentration and disease activity in 56 patients with systemic vasculitis. We included patients with Wegener's granulomatosis, microscopic polyangiitis, idiopathic rapidly progressive glomerulonephritis, and Churg-Strauss syndrome, and examined separately the initial treatment period (mean length of follow-up, 26 months) and long-term management (mean length of follow-up, 59 months). Levels of ANCA decreased during induction therapy with prednisolone and cyclophosphamide, with or without plasma exchange. During follow-up, 27 relapses were documented in 20 patients (10 with Wegener's granulomatosis, nine with microscopic polyangiitis, and one with Churg-Strauss syndrome), occurring between 4 and 183 months (mean, 62 months) after initial presentation. Patients in whom ANCA were detectable 1 year or more after treatment were at particular risk of clinical relapse. Proteinase 3-directed ANCA appeared to be associated with a higher rate of relapse (44% of patients relapsed) than myeloperoxidase-directed ANCA (13% of patients relapsed). Twenty-four of the 27 relapses occurred in the presence of detectable ANCA; in 21 of these, ANCA concentration was high or rising. The temporal relationship between changes in ANCA concentration and clinical relapse varied considerably between patients; in seven patients, ANCA remained at high levels for many months (range, 14 to 67 months) before eventual relapse. One patient showed high concentrations of ANCA over a period of 11 years without relapse. In five patients, increases in the ANCA level were not temporally associated with relapse (although four of these patients relapsed on other occasions.) We conclude that monitoring ANCA by enzyme-linked immunosorbent assays is of value in the long-term management of patients with Wegener's granulomatosis, microscopic polyangiitis, idiopathic rapidly progressive glomerulonephritis, and Churg-Strauss syndrome. Increases in ANCA and persistently high levels point to the risk of relapse and indicate the need for frequent clinical review and continuing maintenance immunosuppression. However, our results suggest that ANCA assays should always be used in conjunction with other indices of disease activity and should not be the sole basis for changing therapy.
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