Interstitial immunostaining and renal outcomes in antineutrophil cytoplasmic antibody-Associated glomerulonephritis

Duvuru Geetha, Sanjeev Sethi, An S. De Vriese, Ulrich Specks, Cees G.M. Kallenberg, Noha Lim, Robert Spiera, E. William St Clair, Peter A. Merkel, Philip Seo, Paul A. Monach, Nicola Lepori, Barri J. Fessler, Carol A. Langford, Gary S. Hoffman, Rishi Sharma, John H. Stone, Fernando C. Fervenza

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Immunopathologic features predict renal function at baseline and follow-up in antineutrophil cytoplasmic antibody (ANCA)-Associated glomerulonephritis (GN). The interstitial infiltrate consists predominantly of T lymphocytes, but their pathophysiologic significance is unclear, especially in light of the success of B-cell-directed therapy. Methods: Renal biopsies from 33 patients treated with cyclophosphamide (CYC; n = 17) or rituximab (RTX; n = 16) in the RTX in ANCA-Associated vasculitis (RAVE) trial were classified according to the new ANCA GN classification. T-And B-cell infiltration in the interstitium was assessed by immunostaining for CD3 and CD20. Correlations of clinical and histologic parameters with renal function at set time points were examined. Results: The mean (SD) baseline estimated glomerular filtration rate was 36 (20) mL/min/1.73 m2. ANCA GN class distribution was 46% focal, 33% mixed, 12% sclerotic and 9% crescentic. The interstitial infiltrate consisted of >50% CD3 positive cells in 69% of biopsies, but >50% CD20 positive cells only in 8% of biopsies. In a multiple linear regression model, only baseline glomerular filtration rate (GFR) correlated with GFR at 6, 12, and 18 months. Interstitial B-And T-cell infiltrates had no significant impact on long-Term prognosis, independent of the treatment limb. A differential effect was noted only at 6 months, where a dense CD3 positive infiltrate predicted lower GFR in the RTX group and a CD20 positive infiltrate predicted higher GFR in the CYC group. Conclusions: In ANCA-Associated GN, the interstitial infiltrate contains mainly T lymphocytes. However, it is neither reflecting baseline renal function nor predictive of response to treatment, regardless of the immunosuppression regimen employed.

Original languageEnglish (US)
Pages (from-to)231-238
Number of pages8
JournalAmerican journal of nephrology
Volume46
Issue number3
DOIs
StatePublished - Sep 1 2017

Keywords

  • Antineutrophil cytoplasmic antibody
  • B cells
  • Rituximab
  • T cells
  • Vasculitis

ASJC Scopus subject areas

  • Nephrology

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    Geetha, D., Sethi, S., De Vriese, A. S., Specks, U., Kallenberg, C. G. M., Lim, N., Spiera, R., St Clair, E. W., Merkel, P. A., Seo, P., Monach, P. A., Lepori, N., Fessler, B. J., Langford, C. A., Hoffman, G. S., Sharma, R., Stone, J. H., & Fervenza, F. C. (2017). Interstitial immunostaining and renal outcomes in antineutrophil cytoplasmic antibody-Associated glomerulonephritis. American journal of nephrology, 46(3), 231-238. https://doi.org/10.1159/000480443