Histologic and immunohistologic study and clinical presentation of ANCA-associated glomerulonephritis with correlation to ANCA antigen specificity.

The major antigen specificities of antineutrophil cytoplasmic antibodies (ANCA) are for proteinase 3 (PR3) and myeloperoxidase (MPO). Only a limited number of studies have systematically assessed renal pathology with respect to ANCA antigen specificity. The authors evaluated renal biopsy light microscopy and immunofluorescence findings, clinical presentation, and outcome in 135 patients with ANCA-associated vasculitides. Patients were divided into 3 groups: PR3-ANCA (n = 55), MPO-ANCA (n = 74), and ANCA of other specificities (n = 6). The mean duration of renal disease at biopsy was significantly longer in patients with MPO-ANCA than in those with PR3-ANCA (6.9 v 3.0 months). Immunofluorescence results showed mostly pauci-immune glomerulonephritis (n = 129) and rarely diffuse granular glomerular immune deposits suggesting immune complex deposition (n = 6). A focal form of crescentic glomerulonephritis was more frequent (P < 0.001), and glomerular necrosis was more prominent (P = 0.013) in the PR3-ANCA group, whereas diffuse crescentic glomerulonephritis, glomerulosclerosis, and interstitial fibrosis predominated in the MPO-ANCA group (P < 0.001). Extraglomerular vasculitis, present in 22.2%, and chronic vascular lesions indicative of previous vasculitis, present in 11.9% of patients, correlated with systemic involvement. The evolution of the pathologic lesions of PR3-ANCA and MPO-ANCA-associated glomerulonephritis seems to be similar. Differences in histopathology could be explained by the observation that in patients with PR3-ANCA, kidney biopsy was performed soon after renal involvement appeared, and focal active lesions were prevalent, whereas in patients with MPO-ANCA, kidney biopsy was done late in the course of the disease, and diffuse chronic sclerotic lesions predominated. Renal extraglomerular small vessel vasculitis appeared to be predictive of systemic involvement.

Vizjak A ，Rott T ，Koselj-Kajtna M ，Rozman B ，Kaplan-Pavlovcic S ，Ferluga D ... -  《-》

An index for renal outcome in ANCA-associated glomerulonephritis.

The aim of this study is to analyze the predictive value of clinical, serological, and histological parameters for renal outcome in antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis by multivariate analysis and create an index valid for clinical use. Data from 160 patients with Wegener's granulomatosis, microscopic polyangiitis, and idiopathic rapidly progressive glomerulonephritis without immune deposits (renal-limited vasculitis) were collected. The Cockcroft formula was used to assess renal function expressed by glomerular filtration rate (GFR) at the time of renal biopsy (t = 0) and 1 year later (t = 1). Other clinical parameters were age, sex, and diagnosis. ANCA test results were scored as cytoplasmic ANCA/antiproteinase 3 (anti-PR3) or perinuclear ANCA/antimyeloperoxidase (anti-MPO) positive or negative. Histological data included normal glomeruli, fibrinoid necrosis, extracapillary proliferation, granulomas, interstitial edema, focal and diffuse infiltrates, fibrosis, tubular cylinders/casts, tubular atrophy, tubular necrosis, sclerosis, mesangial proliferation, mesangial matrix expansion, arteriosclerosis, and infiltrates in arterioles. In a separate analysis, we explored whether there were histological differences between patients with anti-PR3 and anti-MPO ANCA test results. Forty percent of the variation in renal function at the time of biopsy can be explained by the presence or absence of tubular atrophy, normal glomeruli, fibrinoid necrosis, extracapillary proliferation, and age. Renal function at the time of biopsy is the best predictor for renal function at t = 1 in patients with ANCA-associated glomerulonephritis. Together with normal glomeruli, fibrinoid necrosis, and age, it explains more than 60% of the variation in GFR at t = 1. ANCA subtype has no independent contribution in predicting patient prognosis. Results translated into a clinically relevant index: GFR at t = 1 = 36.96 + 0.65* (GFR at t = 0) + 10.52 (if normal glomeruli present) + 7.72 (if fibrinoid necrosis present) - 0.42* (age). The index created with results from this study provides an indication of renal outcome in patients diagnosed with ANCA-associated glomerulonephritis.

Vergunst CE ，van Gurp E ，Hagen EC ，van Houwelingen HC ，Hauer HA ，Noël LH ，Waldherr R ，Ferrario F ，van der Woude FJ ，Bruijn JA ，Bajema IM ，EC/BCR Project for ANCA-Assay Standardisation ... -  《-》

Diagnostic performance of antineutrophil cytoplasmic antibody tests for idiopathic vasculitides: metaanalysis with a focus on antimyeloperoxidase antibodies.

Choi HK ，Liu S ，Merkel PA ，Colditz GA ，Niles JL ... -  《JOURNAL OF RHEUMATOLOGY》

Clinical spectrum associated with ANCA of defined antigen specificities in 98 selected patients.

Geffriaud-Ricouard C ，Noël LH ，Chauveau D ，Houhou S ，Grünfeld JP ，Lesavre P ... -  《CLINICAL NEPHROLOGY》

-463 G/A myeloperoxidase promoter polymorphism is associated with clinical manifestations and the course of disease in MPO-ANCA-associated vasculitis.

Wegener's granulomatosis, microscopic polyangiitis, and Churg Strauss syndrome are forms of systemic vasculitides in which neutrophils and monocyte macrophages infiltrate the walls of small blood vessels, leading to destruction and occlusion. These diseases are associated with autoantibodies directed against granular components of neutrophils and monocytes, i.e., antineutrophil cytoplasmic antibodies (ANCA). The most common target antigens of ANCA in these vasculitides are myeloperoxidase (MPO) and proteinase 3 (PR3). ANCA-stimulated neutrophils injure endothelial cells, a process that is dependent upon the production of reactive oxygen radicals and the release of granular components such as MPO and PR3. Here we investigate whether a common functional MPO promoter polymorphism (-463 G/A) is associated with increased incidence and clinical aspects of ANCA-associated small vessel vasculitis. Genotyping was carried out for 142 patients with ANCA-associated small vessel vasculitis and 129 ethnically matched controls. The GG genotype was found to be associated with an increased risk for MPO-ANCA-associated vasculitis in females (86% GG, P = 0.045), but not males (64% GG, P = 1.0). Interestingly, the MPO A allele is associated with an increased incidence of relapses (P = 0.012) and an earlier age at diagnosis (P = 0.03) of MPO-ANCA-associated vasculitis. Both these associations are specific for MPO-ANCA and are not observed in patients with PR3-ANCA-associated vasculitis. These findings suggest that MPO expression levels influence the disease course of MPO-ANCA-associated vasculitis and further support the view that genetic factors are involved in the pathophysiology of this autoimmune disease.

Reynolds WF ，Stegeman CA ，Tervaert JW 《CLINICAL IMMUNOLOGY》