title: Histologic and immunohistologic study and clinical presentation of ANCA-associated glomerulonephritis with correlation to ANCA antigen specificity.
abstract: BACKGROUND
  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.
  
  
  METHODS
  The authors evaluated renal biopsy light microscopy and immunofluorescence findings, clinical presentation, and outcome in 135 patients with ANCA-associated vasculitides.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. alenka.vizjak@mf.uni-lj.si
authors.forename: Alenka
authors.initials: A
authors.lastname: Vizjak
authors.forename: Tomaz
authors.initials: T
authors.lastname: Rott
authors.forename: Mira
authors.initials: M
authors.lastname: Koselj-Kajtna
authors.forename: Blaz
authors.initials: B
authors.lastname: Rozman
authors.forename: Stasa
authors.initials: S
authors.lastname: Kaplan-Pavlovcic
authors.forename: Dusan
authors.initials: D
authors.lastname: Ferluga
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D000918:Antibody Specificity / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D015267:Churg-Strauss Syndrome / Q000097:blood / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D005921:Glomerulonephritis / Q000097:blood / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000201:enzymology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin; D009195:Peroxidase / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D016896:Treatment Outcome; D014657:Vasculitis / Q000097:blood / Q000201:enzymology / Q000276:immunology / Q000473:pathology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin