Interstitial Immunostaining and Renal Outcomes in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis.

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.

• Authors: 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, RAVE-ITN Research Group
• Journal: American journal of nephrology (Am J Nephrol) Vol. 46 Issue 3 Pg. 231-238 ( 2017) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 28881339 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2017 S. Karger AG, Basel.

Chemical References

• Antibodies, Antineutrophil Cytoplasmic
• Antigens, CD20
• CD3 Complex
• Immunosuppressive Agents
• Rituximab
• Cyclophosphamide

Topics

• Aged
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (blood, drug therapy, immunology, pathology)
• Antibodies, Antineutrophil Cytoplasmic (blood, immunology)
• Antigens, CD20 (analysis)
• B-Lymphocytes (immunology)
• Biopsy
• CD3 Complex (analysis)
• Cyclophosphamide (therapeutic use)
• Female
• Follow-Up Studies
• Glomerular Filtration Rate
• Glomerulonephritis (blood, drug therapy, immunology, pathology)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Kidney (immunology, pathology)
• Male
• Middle Aged
• Prognosis
• Rituximab (therapeutic use)
• T-Lymphocytes (immunology)