Interstitial Foxp3-positive T cells may predict renal survival in patients with myeroperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis

Clin Exp Pharmacol Physiol. 2010 Sep;37(9):879-83. doi: 10.1111/j.1440-1681.2010.05412.x. Epub 2010 May 28.

Abstract

1. Regulatory T cells (T(reg)) and cytotoxic T cells (CTL) are involved in various immune diseases. However, the prognostic impact of T(reg) and CTL in patients with myeroperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) is not well known. Therefore, in the present study, we examined the relationship between expression of forkhead box P3 (Foxp3) and T cell intracytoplasmic antigen (TIA)-1, T(reg) and CTL markers and renal survival in patients with MPO-ANCA-GN. 2. Forty patients with MPO-ANCA-GN and 10 patients with minimal change nephrotic syndrome (MCNS) underwent physical examination, determination of blood chemistry and renal biopsy. Immunohistochemical staining for Foxp3 and TIA-1 was performed on paraffin-embedded renal sections. 3. Although almost all patients received standard immunosuppressive treatment for 6 months, seven MPO-ANCA-GN patients needed maintenance haemodialysis (HD), whereas 33 patients did not (non-HD). Both Foxp3- and TIA-1-positive cells were detected in the interstitium and glomeruli of MPO-ANCA-GN patients, whereas they were rarely detected in patients with MCNS. The total crescent rate was significantly higher in the HD group than in the non-HD group (35.9 +/- 3.5 vs 65.8 +/- 7.4, respectively). In the interstitium, the age-adjusted Foxp3/TIA-1 ratio was significantly higher in the non-HD group than in the HD group (0.016 +/- 0.016 vs 0.004 +/- 0.008, respectively; P < 0.05). The Foxp3/TIA-1 ratio, but not the Foxp3/CD3 ratio, remained significantly higher in the non-HD group than in the HD group even after adjustment for crescent rate. Age- and total crescent rate-adjusted renal survival rates were higher in patients with a Foxp3/TIA-1 ratio > or = 0.06 than in patients with a Foxp3/TIA-1 ratio < 0.06 (P = 0.02). 4. The results of the present study suggest that T(reg) could play a protective role against MPO-ANCA-GN and that a decreased Foxp3/TIA-1 ratio in interstitial areas may predict future renal failure in patients with MPO-ANCA-GN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antineutrophil Cytoplasmic / blood
  • Antibodies, Antineutrophil Cytoplasmic / immunology
  • Antibodies, Antineutrophil Cytoplasmic / metabolism
  • Forkhead Transcription Factors / analysis*
  • Glomerulonephritis / complications
  • Glomerulonephritis / diagnosis*
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / therapy
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney / immunology
  • Kidney / pathology
  • Nephrosis, Lipoid / immunology
  • Peroxidase / immunology
  • Prognosis
  • RNA-Binding Proteins / analysis*
  • Renal Dialysis
  • Renal Insufficiency / etiology*
  • T-Lymphocytes, Cytotoxic* / immunology
  • T-Lymphocytes, Regulatory* / immunology

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunosuppressive Agents
  • RNA-Binding Proteins
  • TIAL1 protein, human
  • Peroxidase