Interstitial Foxp3-positive T cells may predict renal survival in patients with myeroperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.
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.
Yoshimura
Junko
J
Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.
Fukami
Kei
K
Koike
Kiyomi
K
Nagano
Makio
M
Matsumoto
Takafumi
T
Iwatani
Ryuji
R
Kusumoto
Takuo
T
Hazama
Takuma
T
Ueda
Seiji
S
Adachi
Hisashi
H
Hirai
Yuji
Y
Takasu
Konomi
K
Ohshima
Koichi
K
Yamagishi
Sho-ichi
S
Okuda
Seiya
S
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000032:analysis*; D005921:Glomerulonephritis / Q000150:complications / Q000175:diagnosis* / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology / Q000473:pathology; D009402:Nephrosis, Lipoid / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000032:analysis*; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000209:etiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D019268:Antibodies, Antineutrophil Cytoplasmic; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D016601:RNA-Binding Proteins; C076751:TIAL1 protein, human; D009195:Peroxidase