High Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody (ANCA) Level Measured by the Capture Enzyme-Linked Immunosorbent Assay Method Is Associated with Decreased Patient Survival in ANCA-Associated Vasculitis with Renal Involvement

Abstract

Abstract. Wegener granulomatosis (WG) and microscopic polyangiitis (MP), diseases associated with antineutrophil cytoplasmic antibodies (ANCA), had an extremely poor prognosis before the introduction of cyclophosphamide and corticosteroids for their treatment. However, there is still reduced patient survival, and some studies have documented severe side effects of the immunosuppressants used. This 10-yr follow-up study assessed 117 consecutive patients with WG or MP with biopsy-confirmed renal involvement. The cumulative relative patient survival was lower: 0.664 for women and 0.648 for men. The causes of death (n ϭ 64) were in most cases registered as associated with the vasculitic disease. Analysis of possible predictive factors for patient survival by multiple Cox regression analysis revealed that a very high level of proteinase 3 (PR3)-ANCA measured by the capture ELISA method, a diagnosis of MP, and older age were factors predicting poorer patient survival. High levels of B-thrombocytes at time of diagnosis were associated with a better prognosis. For patients surviving the first year, remission-sustaining therapy with azathioprine for longer than 12 mo was associated with improved patient survival. Thirty-nine patients developed end-stage renal failure. Elevated serum creatinine at time of diagnosis and a very high level of PR3-ANCA by capture ELISA were factors predicting a higher risk for renal failure during follow-up. The epitope on PR3 assessed by capture ELISA needs to be further analyzed and explored: it seemed to implicate poorer patient and renal survival in WG or MP with renal involvement.

Outcome and Treatment of Elderly Patients with ANCA-Associated Vasculitis

“…In our cohort, 15% of the patients had a previous malignancy before the diagnosis of AAV. This is similar to other studies showing a frequency of malignancies of 8%-16% (17,22 (23). The effect of differences in life expectancies in the general population when comparing the survival of AAV is difficult to discern.…”

“…High age and impaired renal function have previously been shown to predict mortality in younger age groups as well (6,11,14,(17)(18)(19)(20). The inverse relationship between BVAS and survival is intriguing and opposite of some previous findings (11,18).…”

“…Comorbidities were more common in Czech patients; only 16% had no comorbidities compared with 47% and 40% of the Swedish and English patients, respectively (P,0.001). Median BVAS was 12 (IQR, 9-12) in patients with renal-limited disease and 16 (IQR, [13][14][15][16][17][18][19] in patients with more than one organ system involved (P,0.001).…”

Translational Mini-Review Series on Immunology of Vascular Disease: Accelerated atherosclerosis in vasculitis

“…Several studies have now shown that, during long-term follow-up, cardiovascular disease is a major cause of mortality in patients with ANCA-associated vasculitis [40][41][42][43][44][45][46][47][48]. Zaenker et al reported that patients with Wegener's granulomatosis had a higher frequency of cardiovascular diseases compared with healthy controls [odds ratio (OR) 6·7] [49].…”

Drug Induced Small Vessel Vasculitis

“…The combination of PR3-ANCA with normal neutrophils fixed with acetone produces a typical cytoplasmic discoloration, and hence the term C-ANCA. The MPO-ANCA induces a perinuclear change known as P-ANCA (Westman K, et al, 2003). Other drugs that cause DIL and DIV include, but are not limited to: carbamazepine, chlorpromazine, isoniazide, methimazole, alpha methyldopa, mynocicline, phenytoin, procainamide and quinidine (Ullman S. et al, 2004).…”