Wegener's granulomatosis: inflammatory cells and markers of repair and fibrosis in renal biopsies--a clinicopathological study

Scand J Urol Nephrol. 2001 Oct;35(5):401-10. doi: 10.1080/003655901753224477.

Abstract

Objective: This study aimed to quantitate inflammatory cells in renal biopsies from patients with Wegener's granulomatosis (WG) and to identify cells participating in early fibrogenesis. The goal was to determine whether these cells correlated with the severity of renal disease and whether their presence had a bearing on renal prognosis.

Material and methods: Sixty-one patients with WG who had a renal biopsy taken at the time of diagnosis were included in the study. Immunostaining with monoclonal antibodies towards macrophages (CD68), T- and B-lymphocytes, alpha-smooth muscle actin (alpha-SMA) and vimentin was done.

Results: The dominating intraglomerular leucocytes were macrophages (29.9 +/- 15 cells/glomerular cross-section) and to a lesser extent T-cells (2.57 +/- 1.8 cells/glomerular cross-section). No B-lymphocytes were detected in the glomeruli. More than two-thirds of the T-cells were CD8+ (cytotoxic) cells. Macrophages and T-lymphocytes were distributed equally in the renal interstitium and were numerous around crescentic glomeruli. Glomerular and interstitial macrophages and interstitial T-cells correlated significantly with serum (S-) creatinine at the time of biopsy but not after 1 year. S-creatinine at the time of biopsy and after 1 year differed significantly among the three levels of interstitial alpha-SMA staining. S-creatinine at biopsy was highest when tubular vimentin staining was strongest, and tubular vimentin staining was strongest in patients with acute tubular damage.

Conclusions: Evidence was found for a cellular type IV immune response in WG, with CD8+ T-lymphocytes and macrophages dominating the cellular infiltrate. The detection of interstitial alpha-SMA, probably staining myofibroblasts implicated in renal fibrogenesis, indicated a low glomerular filtration rate 1 year after renal biopsy.

MeSH terms

  • Actins / analysis
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / analysis
  • Biomarkers / analysis
  • Biopsy
  • Creatinine / blood
  • Female
  • Fibrosis / blood
  • Granulomatosis with Polyangiitis / metabolism
  • Granulomatosis with Polyangiitis / pathology*
  • Granulomatosis with Polyangiitis / physiopathology
  • Humans
  • Immunohistochemistry
  • Inflammation / metabolism
  • Inflammation / pathology
  • Kidney / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Severity of Illness Index
  • Vimentin / analysis

Substances

  • Actins
  • Antigens, CD
  • Biomarkers
  • Vimentin
  • Creatinine