间质中 Foxp3 阳性 T 细胞可能有助于预测髓过氧化物酶抗中性粒细胞胞质抗体相关性肾小球肾炎患者的肾脏存活率。

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

机构信息

Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.

出版信息

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

DOI:10.1111/j.1440-1681.2010.05412.x

PMID:20528980

Abstract

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.

摘要

调节性 T 细胞（Treg）和细胞毒性 T 细胞（CTL）参与多种免疫疾病。然而，髓过氧化物酶抗中性粒细胞胞质抗体相关性肾小球肾炎（MPO-ANCA-GN）患者中 Treg 和 CTL 的预后影响尚不清楚。因此，本研究探讨了叉头框 P3（Foxp3）和 T 细胞胞质内抗原（TIA）-1、Treg 和 CTL 标志物在 MPO-ANCA-GN 患者中的表达与肾脏生存之间的关系。
40 例 MPO-ANCA-GN 患者和 10 例微小病变性肾病综合征（MCNS）患者接受了体格检查、血液化学测定和肾活检。对石蜡包埋的肾切片进行 Foxp3 和 TIA-1 的免疫组织化学染色。
尽管几乎所有患者都接受了 6 个月的标准免疫抑制治疗，但 7 例 MPO-ANCA-GN 患者需要维持性血液透析（HD），而 33 例患者则不需要（非-HD）。MPO-ANCA-GN 患者的间质和肾小球中均检测到 Foxp3-和 TIA-1 阳性细胞，而 MCNS 患者中很少检测到。HD 组的总新月体形成率明显高于非-HD 组（35.9%±3.5%对 65.8%±7.4%）。在间质中，非-HD 组的 Foxp3/TIA-1 比值明显高于 HD 组（0.016±0.016 对 0.004±0.008，P<0.05）。即使在调整新月体形成率后，非-HD 组的 Foxp3/TIA-1 比值仍明显高于 HD 组。Foxp3/TIA-1 比值，而不是 Foxp3/CD3 比值，在调整年龄和总新月体形成率后，非-HD 组仍明显高于 HD 组。Foxp3/TIA-1 比值≥0.06 的患者的肾脏生存率高于 Foxp3/TIA-1 比值<0.06 的患者（P=0.02）。
本研究结果表明，Treg 可能对 MPO-ANCA-GN 具有保护作用，间质中 Foxp3/TIA-1 比值降低可能预测 MPO-ANCA-GN 患者的未来肾衰竭。