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急性肾移植排斥反应中B细胞的表达模式。

Expression patterns of B cells in acute kidney transplant rejection.

作者信息

Carpio Virna Nowotny, Noronha Irene de Lourdes, Martins Hugo Ludovico, Jobim Luiz Fernando, Gil Beatriz Chamun, Külzer Adriane Silva, Loreto Melina da Silva, Gonçalves Luiz Felipe Santos, Manfro Roberto Ceratti, Veronese Francisco Veríssimo

机构信息

From the Postgraduate Program in Medicine/Medical Sciences, Federal University of Rio Grande do Sul, Division of Nephrology and Laboratory of Molecular Biology Applied to Nephrology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.

出版信息

Exp Clin Transplant. 2014 Oct;12(5):405-14.

Abstract

OBJECTIVES

To evaluate B-cell expression patterns and association with function and survival in dysfunctional kidney allografts.

MATERIALS AND METHODS

There were 110 kidney transplant recipients included who had for-cause biopsies. Demographic and transplant data were collected. Immunostaining for B cells, plasma cells, and C4d was performed by the immunoperoxidase technique in paraffin-embedded samples. Circulating antihuman leukocyte antigen donor-specific antibodies were detected in a single-antigen assay at biopsy. The main outcomes were kidney graft survival and function. The patients were evaluated in 3 groups according to the Banff classification: no rejection (40 patients), T-cell-mediated rejection (50 patients), and antibody-mediated rejection (20 patients).

RESULTS

The CD138-positive plasma cell-rich infiltrates predominated in antibody-mediated rejection and were associated with stronger reactivity against panel antibodies (r = 0.41; P ≤ .001) and positive donor-specific antibodies (r = 0.32; P ≤ .006). The CD20-positive lymphocytes were associated with T-cell-mediated rejection, increased human leukocyte antigen mismatch, and frequency of retransplant. The CD138-positive cell infiltrates also were significantly greater in patients who had late than early rejection. There was no correlation between cellular CD20 and CD138 expression, and neither CD20 nor CD138 predicted worse graft function or survival. Other markers of antibody-mediated rejection such as C4d and donor-specific antibodies were associated with worse graft function and survival at 4 years after transplant. In multivariate analysis, C4d was the only risk factor associated with graft loss.

CONCLUSIONS

After kidney transplant, CD20-positive B-cell infiltrates were associated with T-cell-mediated rejection, and CD138-positive plasma cells were associated with antibody-mediated rejection. Graft loss was associated with the presence of C4d.

摘要

目的

评估功能失调的肾移植受者中B细胞的表达模式及其与功能和生存的关系。

材料与方法

纳入110例行因病因活检的肾移植受者。收集人口统计学和移植数据。采用免疫过氧化物酶技术对石蜡包埋样本中的B细胞、浆细胞和C4d进行免疫染色。在活检时通过单抗原检测法检测循环中的抗人白细胞抗原供体特异性抗体。主要观察指标为肾移植的存活和功能。根据Banff分类将患者分为3组:无排斥反应(40例患者)、T细胞介导的排斥反应(50例患者)和抗体介导的排斥反应(20例患者)。

结果

在抗体介导的排斥反应中,富含CD138阳性浆细胞的浸润占主导地位,且与针对一组抗体的更强反应性相关(r = 0.41;P≤0.001)以及供体特异性抗体阳性相关(r = 0.32;P≤0.006)。CD20阳性淋巴细胞与T细胞介导的排斥反应、人白细胞抗原错配增加及再次移植频率相关。CD138阳性细胞浸润在晚期排斥反应患者中也显著多于早期排斥反应患者。细胞CD20和CD138表达之间无相关性,且CD20和CD138均不能预测移植肾功能更差或存活情况更差。抗体介导的排斥反应的其他标志物如C4d和供体特异性抗体与移植后4年的移植肾功能更差和存活情况更差相关。在多变量分析中,C4d是与移植肾丢失相关的唯一危险因素。

结论

肾移植后,CD20阳性B细胞浸润与T细胞介导的排斥反应相关,而CD138阳性浆细胞与抗体介导的排斥反应相关。移植肾丢失与C4d的存在相关。

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