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肾移植中富含浆细胞排斥反应的临床病理及免疫组化分析:肾小管内Th1/Th2平衡在浆细胞富集中的作用

Clinicopathological and immunohistochemical analysis of plasma cell-rich rejection in renal transplantation: Involvement of intratubular Th1/Th2 balance in plasma cell enrichment.

作者信息

Nishimura Ayako, Masuzawa Naoko, Nakamura Tsukasa, Harada Shumpei, Nobori Shuji, Ushigome Hidetaka, Yoshimura Norio, Konishi Eiichi

机构信息

Division of Surgical Pathology, Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Department of Diagnostic Pathology, Otsu City Hospital, Shiga, Japan.

出版信息

Nephrology (Carlton). 2018 Jul;23 Suppl 2:52-57. doi: 10.1111/nep.13273.

Abstract

AIM

Plasma cell-rich rejection (PCRR) has been considered a subtype of acute T-cell-mediated rejection (ATCR). However, PCRR is recognized as refractory rejection and different from ATCR in various ways. In order to elucidate the pathogenesis of PCRR, we analysed PCRR clinicopathologically and immunohistochemically by comparing it with ATCR.

METHODS

Twelve cases of PCRR (PCRRs) and 22 cases of usual ATCR (ATCRs) diagnosed at our hospital between January 2008 and March 2017 were included. Between PCRRs and ATCRs, we compared clinical data, Banff classification, graft outcome and the total sum number of T-bet- and GATA3-positive lymphocytes infiltrating in tubular epithelium using immunohistochemistry.

RESULTS

Plasma cell-rich rejections occurred later than ATCRs (median time after transplantation 1340.5 days vs. 52.5 days). Serum creatinine levels at discharge after treatment were significantly higher in PCRRs than in ATCRs (median 2.38 vs. 1.65 mg/dL). Cumulative rate of graft loss was significantly higher in PCRRs than in ATCRs (1-, 2- and 5-year: 26.7%, 51.1% and 51.1% vs. 0%, 0% and 17.5%). For profiles of Th1 and Th2, we found significantly lower ratio of T-bet/GATA3-positive lymphocytes in PCRRs compared with ATCRs.

CONCLUSION

This study suggests that PCRR is more refractory than ATCR and there are significant differences in populations of helper T-cell subsets between them. We consider helper T-cell subset analysis valuable for developing new treatment strategies for PCRR.

摘要

目的

富含浆细胞的排斥反应(PCRR)被认为是急性T细胞介导的排斥反应(ATCR)的一种亚型。然而,PCRR被认为是难治性排斥反应,并且在多种方面与ATCR不同。为了阐明PCRR的发病机制,我们通过将PCRR与ATCR进行比较,对其进行了临床病理和免疫组织化学分析。

方法

纳入2008年1月至2017年3月在我院诊断的12例PCRR(PCRR组)和22例普通ATCR(ATCR组)。我们比较了PCRR组和ATCR组之间的临床数据、Banff分级、移植物结局以及使用免疫组织化学检测的浸润于肾小管上皮的T-bet和GATA3阳性淋巴细胞总数。

结果

富含浆细胞的排斥反应比ATCR发生得晚(移植后中位时间1340.5天对52.5天)。治疗后出院时PCRR组的血清肌酐水平显著高于ATCR组(中位值2.38对1.65mg/dL)。PCRR组的移植物丢失累积率显著高于ATCR组(1年、2年和5年:26.7%、51.1%和51.1%对0%、0%和17.5%)。对于Th1和Th2谱,我们发现与ATCR组相比,PCRR组中T-bet/GATA3阳性淋巴细胞的比例显著更低。

结论

本研究表明PCRR比ATCR更难治,并且它们之间辅助性T细胞亚群的群体存在显著差异。我们认为辅助性T细胞亚群分析对于开发PCRR的新治疗策略具有重要价值。

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