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移植肾T细胞介导的排斥反应的病理学

郭晖

郭晖. 移植肾T细胞介导的排斥反应的病理学[J]. 器官移植, 2021, 12(2): 134-142. doi: 10.3969/j.issn.1674-7445.2021.02.003
引用本文: 郭晖. 移植肾T细胞介导的排斥反应的病理学[J]. 器官移植, 2021, 12(2): 134-142. doi: 10.3969/j.issn.1674-7445.2021.02.003
Guo Hui. Pathology of T cell-mediated rejection in renal allograft[J]. ORGAN TRANSPLANTATION, 2021, 12(2): 134-142. doi: 10.3969/j.issn.1674-7445.2021.02.003
Citation: Guo Hui. Pathology of T cell-mediated rejection in renal allograft[J]. ORGAN TRANSPLANTATION, 2021, 12(2): 134-142. doi: 10.3969/j.issn.1674-7445.2021.02.003

移植肾T细胞介导的排斥反应的病理学

doi: 10.3969/j.issn.1674-7445.2021.02.003
基金项目: 

中国医学科学院中央级公益性科研院所基本科研业务费专项资金资助 2019PT320014

详细信息
    通讯作者:

    郭晖,研究方向为移植病理学基础与临床应用研究,E-mail:zcguo@tjh.tjmu.edu.cn

  • 中图分类号: R617, R36

Pathology of T cell-mediated rejection in renal allograft

More Information
  • 摘要: T细胞介导的排斥反应(TCMR)是器官移植排斥反应的主要效应机制之一, 也是最常见的急性排斥反应类型。2019年Banff移植病理学诊断标准(Banff标准)根据免疫损伤病变的特征将TCMR分为急性TCMR (aTCMR)和慢性活动性TCMR (caTCMR)。本文对TCMR的基本定义、移植肾Banff标准中TCMR病理学的研究历程和TCMR的基本病变及其诊断分级进行综述, 旨在为早期识别、诊断和治疗TCMR提供依据, 以预防其进展为caTCMR, 进而保障移植肾和受者的长期存活。
  • 图  1  移植肾aTCMR的病理学表现(HE,×200)

    注:图示移植肾间质内炎症细胞浸润。

    Figure  1.  Pathological findings of aTCMR in renal allograft

    图  2  移植肾aTCMR的肾小管炎病理学表现

    注: A图示肾小管内2个炎症细胞浸润, 为轻度肾小管炎(t1)(HE, × 400);B图示肾小管内>4个炎症细胞浸润, 为中度肾小管炎(t2)(HE, × 400);C图示肾小管内>10个炎症细胞浸润, 为重度肾小管炎(t3)(PAS, × 400);D图示肾小管炎时CD8+T细胞浸润于肾小管上皮层(免疫组织化学, × 400)。

    Figure  2.  Pathological findings of tubulitis of aTCMR in renal allograft

    图  3  移植肾aTCMR的动脉内膜炎病理学表现

    注: A图示动脉内膜上炎症细胞浸润呈轻度动脉内膜炎(v1)(HE, × 200);B图示动脉内膜炎症细胞浸润及局部水肿致25%的管腔狭窄, 为中度动脉内膜炎(v2)(HE, × 400);C图示动脉管壁全层炎症细胞浸润, 为重度动脉内膜炎(v3)(HE, × 200);D图示动脉管壁纤维素样坏死, 为重度动脉内膜炎(v3)(HE, × 200)。

    Figure  3.  Pathological findings of endoarteritis of aTCMR in renal allograft

    图  4  移植肾caTCMR的CAV病理学表现

    注: A图示动脉内膜轻度增生, 管腔狭窄程度<25%, 为轻度CAV (cv1)(HE, × 400);B图示动脉内膜中度增生, 管腔狭窄程度在26%~50%, 为中度CAV (cv2)(HE, × 200);C图示动脉内膜重度增生, 管腔狭窄程度>50%, 增生的动脉内膜内可见炎症细胞浸润, 提示急性排斥反应仍在进展, 为重度CAV (cv3)(HE, × 200);D图示小动脉内膜重度增生>50%, 管腔接近闭塞, 为重度CAV (cv3)(HE, × 200)。

    Figure  4.  Pathological findings of CAV of caTCMR in renal allograft

    图  5  移植肾i-IFTA的病理学表现

    注:图示移植肾IFTA区域内炎症细胞浸润(PAS,× 200)。

    Figure  5.  Pathological findings of i-IFTA in renal allograft

    图  6  移植肾t-IFTA的病理学表现

    注: 图示IFTA区域内炎症细胞浸润以及萎缩的肾小管上皮内炎症细胞浸润呈萎缩肾小管炎, A图(PAS, × 200);B图(PASM, × 400)。

    Figure  6.  Pathological findings of t-IFTA in renal allograft

    表  1  移植肾急性病理学改变及其半定量计分

    Table  1.   Acute pathological changes of renal allograft and its semi-quantitative scoring

    计分
    (分)
    间质炎症细胞浸润(i) 肾小管炎(t) 肾小球炎(g) 动脉内膜炎(v)
    0 无或仅有轻微的间质炎症细胞浸润(< 10%的肾间质被累及) 肾小管上皮层内无单个核炎症细胞浸润 无肾小球炎 无动脉内膜炎
    1 10°%~25°%的肾间质被炎症细胞浸润累及 个别肾小管管腔有1~4个炎症细胞浸润或10个肾小管上皮细胞内有1~4个炎症细胞浸润 < 25%的肾小球出现肾小球炎 至少在1支动脉血管分支横截面内可见轻度至中度动脉内膜炎
    2 26°%~50°%的肾间质被炎症细胞浸润累及 个别肾小管管腔有5~10个炎症细胞浸润或10个肾小管上皮细胞内有5~10个炎症细胞浸润 25%~75°%的肾小球出现肾小球炎 至少在1支动脉血管分支横截面内存在严重的动脉内膜炎, 因内膜水肿增厚导致至少25°%的动脉管腔丧失
    3 > 50°%的肾间质被炎症细胞浸润累及 个别肾小管管腔有 > 10个炎症细胞浸润, 或出现至少2个部位的肾小管基膜损伤并伴有i2或i3和t2 > 75°%的肾小球出现肾小球炎 透壁性动脉炎、动脉中膜平滑肌层坏死或动脉管壁纤维素样坏死
    注:①对于浸润的炎症细胞中出现嗜酸性粒细胞、中性粒细胞或浆细胞并且这些细胞数量超过浸润细胞总数的10%者,应予以注明。
    ②注明活检组织内可见多少动脉血管分支,多少动脉被累及以及肾组织是否出现梗死、出血。
    下载: 导出CSV

    表  2  移植肾慢性病理学改变及其半定量计分

    Table  2.   Chronic pathological changes of renal allograft and its semi-quantitative scoring

    计分
    (分)
    肾小球病(cg) 间质纤维化(ci) 肾小管萎缩(ct) 动脉内膜增生(cv) 肾小球毛细血管系
    膜基质增生(mm)
    0 无肾小球病, 在多数病变的肾小球内, 肾小球血管襻外周毛细血管基底膜呈双轨状变化的肾小球 < 10°% 间质纤维化累及肾皮质组织的5% 无肾小管萎缩 动脉血管无慢性血管病变 肾小球内无系膜基质增生
    1 在多数非硬化肾小球内, 肾小球血管襻外周毛细血管基底膜呈双轨状变化的肾小球接近25% 间质纤维化累及肾皮质组织的6%~25% 肾皮质组织内 < 25°%的肾小管萎缩 动脉内膜增生形成管腔狭窄导致管腔闭塞 < 25%, 伴或不伴动脉内弹力膜的损伤或内膜泡沫细胞形成以及炎症细胞浸润 < 25%的非硬化肾小球内出现系膜基质增生(至少为中度增生)
    2 在多数非硬化肾小球内, 肾小球血管襻外周毛细血管基底膜呈双轨状变化的肾小球达到26%~50% 间质纤维化累及肾皮质组织的26%~50% 肾皮质组织内26%~50%的肾小管萎缩 cv1的病变进一步进展, 动脉内膜增生导致管腔狭窄使管腔闭塞26%~50% 26%~50%的非硬化肾小球内出现系膜基质增生(至少为中度增生)
    3 在多数非硬化肾小球内, 肾小球血管襻外周毛细血管基底膜呈双轨状变化的肾小球 > 50% 间质纤维化累及 > 50%的肾皮质组织 肾皮质组织内 > 50°%的肾小管萎缩 严重的慢性动脉血管病变, 动脉内膜增生致管腔狭窄使管腔闭塞 > 50% > 50%的非硬化肾小球内出现系膜基质增生(至少为中度增生)
    下载: 导出CSV
  • [1] 中华医学会器官移植学分会. 器官移植病理学临床技术操作规范(2019版)--总论与肾移植[J]. 器官移植, 2019, 10(2): 128-141. DOI: 10.3969/j.issn.1674-7445.2019.02.004.

    Branch of Organ Transplantation of Chinese Medical Association. Clinical technical operation specification for pathology of organ transplantation (2019 edition): general introduction and kidney transplantation[J]. Organ Transplant, 2019, 10(2): 128-141. DOI: 10.3969/j.issn.1674-7445.2019.02.004.
    [2] 陈实, 郭晖. 移植病理学[M]. 北京: 人民卫生出版社, 2009.
    [3] LOUPY A, HAAS M, ROUFOSSE C, et al. The Banff 2019 kidney meeting report (I): updates on and clarification of criteria for T cell-and antibody-mediated rejection[J]. Am J Transplant, 2020, 20(9): 2318-2331. DOI: 10.1111/ajt.15898.
    [4] SOLEZ K, AXELSEN RA, BENEDIKTSSON H, et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology[J]. Kidney Int, 1993, 44(2): 411-422. DOI: 10.1038/ki.1993.259.
    [5] SOLEZ K, BENEDIKTSSON H, CAVALLO T, et al. Report of the third Banff conference on allograft pathology (July 20-24, 1995) on classification and lesion scoring in renal allograft pathology[J]. Transplant Proc, 1996, 28(1): 441-444. http://europepmc.org/abstract/med/8644308
    [6] RACUSEN LC, SOLEZ K, COLVIN RB, et al. The Banff 97 working classification of renal allograft pathology[J]. Kidney Int, 1999, 55(2): 713-723. DOI: 10.1046/j.1523-1755.1999.00299.x.
    [7] SOLEZ K. History of the Banff classification of allograft pathology as it approaches its 20th year[J]. Curr Opin Organ Transplant, 2010, 15(1): 49-51. DOI: 10.1097/MOT.0b013e328334fedb.
    [8] SOLEZ K, COLVIN RB, RACUSEN LC, et al. Banff'05 meeting report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN')[J]. Am J Transplant, 2007, 7(3): 518-526. DOI: 10.1111/j.1600-6143.2006.01688.x.
    [9] SOLEZ K, COLVIN RB, RACUSEN LC, et al. Banff 07 classification of renal allograft pathology: updates and future directions[J]. Am J Transplant, 2008, 8(4): 753-760. DOI: 10.1111/j.1600-6143.2008.02159.x.
    [10] BURDICK JF, BESCHORNER WE, SMITH WJ, et al. Characteristics of early routine renal allograft biopsies[J]. Transplantation, 1984, 38(6): 679-684. DOI: 10.1097/00007890-198412000-00026.
    [11] OLSEN S, BURDICK JF, KEOWN PA, et al. Primary acute renal failure ("acute tubular necrosis") in the transplanted kidney: morphology and pathogenesis[J]. Medicine (Baltimore), 1989, 68(3): 173-187. DOI: 10.1097/00005792-198905000-00005.
    [12] BATES WD, DAVIES DR, WELSH K, et al. An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome[J]. Nephrol Dial Transplant, 1999, 14(10): 2364-2369. DOI: 10.1093/ndt/14.10.2364.
    [13] ISONIEMI H, TASKINEN E, HÄYRY P. Histological chronic allograft damage index accurately predicts chronic renal allograft rejection[J]. Transplantation, 1994, 58(11): 1195-1198. doi: 10.1097/00007890-199412150-00010
    [14] SOLEZ K, RACUSEN LC. The Banff classification revisited[J]. Kidney Int, 2013, 83(2): 201-206. DOI: 10.1038/ki.2012.395.
    [15] LOUPY A, HAAS M, SOLEZ K, et al. The Banff 2015 kidney meeting report: current challenges in rejection classification and prospects for adopting molecular pathology[J]. Am J Transplant, 2017, 17(1): 28-41. DOI: 10.1111/ajt.14107.
    [16] NIN M, COITIÑO R, KURDIAN M, et al. Acute antibody-mediated rejection in kidney transplant based on the 2013 Banff criteria: single-center experience in Uruguay[J]. Transplant Proc, 2016, 48(2): 612-615. DOI: 10.1016/j.transproceed.2016.03.019.
    [17] SHIMIZU T, ISHIDA H, HAYAKAWA N, et al. Clinical and pathological analyses of cases of acute vascular rejection after kidney transplantation[J]. Transplant Proc, 2017, 49(10): 2251-2255. DOI: 10.1016/j.transproceed.2017.09.046.
    [18] HAAS M, LOUPY A, LEFAUCHEUR C, et al. The Banff 2017 kidney meeting report: revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials[J]. Am J Transplant, 2018, 18(2): 293-307. DOI: 10.1111/ajt.14625.
    [19] 黄亚冰, 郭晖, 钟伟雄. 2017年Banff移植病理学会议纪要及移植肾病理诊断分类修订[J]. 中华器官移植杂志, 2018, 39(9): 565-570. DOI: 10.3760/cma.j.issn.0254-1785.2018.09.011.

    HUANG YB, GUO H, ZHONG WX. 2017 Banff allograft pathology conference summary and revised classification of transplant kidney pathology[J]. Chin J Organ Transplant, 2018, 39(9): 565-570. DOI: 10.3760/cma.j.issn.0254-1785.2018.09.011.
    [20] PASCUAL J, PÉREZ-SÁEZ MJ, MIR M, et al. Chronic renal allograft injury: early detection, accurate diagnosis and management[J]. Transplant Rev (Orlando), 2012, 26(4): 280-290. http://europepmc.org/abstract/MED/22902496
    [21] WILSON PC, KASHGARIAN M, MOECKEL G.Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis[J].Clin Kidney J, 2018, 11(2): 207-218.DOI: 10.1093/ckj/sfx093.
    [22] MENGEL M, REEVE J, BUNNAG S, et al.Scoring total inflammation is superior to the current Banff inflammation score in predicting outcome and the degree of molecular disturbance in renal allografts[J].Am J Transplant, 2009, 9(8): 1859-1867.DOI: 10.1111/j.1600-6143.2009.02727.x.
    [23] MANNON RB, MATAS AJ, GRANDE J, et al.Inflammation in areas of tubular atrophy in kidney allograft biopsies: a potent predictor of allograft failure[J].Am J Transplant, 2010, 10(9): 2066-2073.DOI: 10.1111/j.1600-6143.2010.03240.x.
    [24] HUESO M, NAVARRO E, MORESO F, et al.Intragraft expression of the IL-10 gene is up-regulated in renal protocol biopsies with early interstitial fibrosis, tubular atrophy, and subclinical rejection[J].Am J Pathol, 2010, 176(4): 1696-1704.DOI: 10.2353/ajpath.2010.090411.
    [25] LEFAUCHEUR C, GOSSET C, RABANT M, et al.T cell-mediated rejection is a major determinant of inflammation in scarred areas in kidney allografts[J].Am J Transplant, 2018, 18(2): 377-390.DOI: 10.1111/ajt.14565.
    [26] NANKIVELL BJ, SHINGDE M, KEUNG KL, et al.The causes, significance and consequences of inflammatory fibrosis in kidney transplantation: the Banff i-IFTA lesion[J].Am J Transplant, 2018, 18(2): 364-376.DOI: 10.1111/ajt.14609.
    [27] LEFAUCHEUR C, VIGLIETTI D, LOUPY A.Recognition of i-IF/TA as a component of the T cellmediated rejection spectrum: unselected population approach vs random case selection[J].Am J Transplant, 2018, 18(3): 771-772.DOI: 10.1111/ajt.14667.
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  • 收稿日期:  2021-01-25
  • 网络出版日期:  2021-03-19
  • 刊出日期:  2021-03-15

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