Tissue-based Gene Expression Diagnosis of Mild and Moderate T-cell-mediated Rejection to Guide Therapy in Kidney Transplants.

IF 5 2区医学 Q1 IMMUNOLOGY

Transplantation Pub Date : 2025-08-01 Epub Date: 2024-12-23 DOI:10.1097/TP.0000000000005296

Dhiren Kumar, Nihar Raju, Bekir Tanriover, Louiza Azzouz, Irfan Moinuddin, Mary Philogene, Layla Kamal, Felecia McDougan, Hugh Davis Massey, Selvaraj Muthusamy, Inkoo Lee, Philip Halloran, Gaurav Gupta

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引用次数: 0

Abstract

Background: Mild histologic lesions of tubulo-interstitial inflammation could represent a "response-to-wounding" rather than allorecognition. Tissue gene expression may complement histopathology for T-cell-mediated rejection (TCMR) diagnostics.

Methods: We report on the incorporation of tissue gene expression testing using a Molecular Microscope Diagnostic System into the management of kidney transplant biopsies with suspected TCMR. Patients (N = 209) were divided into 3 groups based upon diagnosis and TCMR therapy (with high-dose steroids and/or anti-thymocyte globulin): Group 1: Untreated histologic TCMR with molecular quiescence (H+M-); Group 2: Treated histologic and molecular TCMR (H+M+); and Group 3: Controls, with no histologic or molecular (H-M-) rejection.

Results: At biopsy, estimated glomerular filtration rate was worse ( P = 0.006) in H+M+ (N = 35; 33 ± 22 mL/min/1.73 m 2 ) and H+M- (N = 30; 40 ± 18 mL/min/1.73 m 2 ) groups; compared with H-M- (N = 144; 47 ± 24 mL/min/1.73 m 2 ) group. In H+M- biopsies, mean molecular acute kidney injury scores (0.33 versus 0.10; P = 0.03) were higher than in H-M-; while molecular TCMR was lower compared with H+M+ (0.04 versus 0.54; P < 0.001). At 12 m postbiopsy estimated glomerular filtration rate remained low ( P < 0.001) in H+M+ (38 ± 22 mL/min/1.73 m 2 ) but improved in untreated H+M- (44 ± 22 mL/min/1.73 m 2 ) and H-M- (50 ± 23 mL/min/1.73 m 2 ) groups. At a mean follow-up of 2.1 ± 1.2 y post-index biopsy, death-censored graft survival was lower in H+M+ (74%) than in H+M- (90%) and H-M- (92%; P = 0.001). H+M+ cases had numerically higher rejection on follow-up biopsy (20%) than H+M- (7%) ( P = 0.12) and de novo donor-specific antibody formation (H+M+ 24%; H+M- 10%; P = 0.13).

Conclusions: In this large single-center study, biopsies with untreated histological TCMR and molecular quiescence had comparable clinical outcomes to cases with no rejection, whereas those with histologic and tissue gene expression confirmed TCMR had inferior outcomes.

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轻度和中度t细胞介导的排斥反应的组织基因表达诊断指导肾移植治疗。

背景：小管间质炎症的轻度组织学病变可能代表“对伤害的反应”，而不是同种异体识别。组织基因表达可以补充组织病理学诊断t细胞介导的排斥反应（TCMR）。方法：我们报道使用分子显微镜诊断系统将组织基因表达检测纳入可疑TCMR肾移植活检的管理。209例患者根据诊断和TCMR治疗（大剂量类固醇和/或抗胸腺细胞球蛋白）分为3组：1组：未经治疗的组织学TCMR伴分子静止（H+M-）；2组：经治疗的组织学和分子TCMR (H+M+)；第3组：对照组，无组织或分子（H-M-）排斥反应。结果：活检时，H+M+组肾小球滤过率较差（P = 0.006） (N = 35；33±22 mL/min/1.73 m2)和H+M- (N = 30；40±18 mL/min/1.73 m2)组；H-M- (N = 144)；47±24 mL/min/1.73 m2)组。在H+M活检中，平均分子急性肾损伤评分(0.33 vs 0.10；P = 0.03)高于H-M-组；而分子TCMR较H+M+低(0.04比0.54；P < 0.001)。活检后12 m时，H+ m +组肾小球滤过率仍较低（P < 0.001）（38±22 mL/min/1.73 m2），但未治疗的H+ m -组（44±22 mL/min/1.73 m2）和H- m -组（50±23 mL/min/1.73 m2）有所改善。在指数活检后平均随访2.1±1.2 y时，H+M+组（74%）的死亡剔除移植物存活率低于H+M-组（90%）和H-M-组（92%）；P = 0.001)。在随访活检中，H+M+病例的排斥反应（20%）高于H+M- (7%) （P = 0.12）和新生供者特异性抗体形成(H+M+ 24%；H + M - 10%;P = 0.13)。结论：在这项大型单中心研究中，未经治疗的组织学TCMR和分子静止活检的临床结果与没有排斥反应的病例相当，而组织学和组织基因表达证实TCMR的患者预后较差。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.