基于组织的轻度和中度T细胞介导排斥反应的基因表达诊断以指导肾移植治疗

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

作者信息

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

机构信息

Division of Nephrology, Virginia Commonwealth University, Richmond, VA.

Division of Nephrology, University of Arizona, Tucson, AZ.

出版信息

Transplantation. 2024 Dec 23. doi: 10.1097/TP.0000000000005296.

DOI:10.1097/TP.0000000000005296

PMID:39710875

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 m2) and H+M- (N = 30; 40 ± 18 mL/min/1.73 m2) groups; compared with H-M- (N = 144; 47 ± 24 mL/min/1.73 m2) 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 m2) but improved in untreated H+M- (44 ± 22 mL/min/1.73 m2) and H-M- (50 ± 23 mL/min/1.73 m2) 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.

摘要

背景

肾小管间质性炎症的轻度组织学病变可能代表一种“创伤反应”而非同种异体识别。组织基因表达可能有助于补充组织病理学用于T细胞介导的排斥反应（TCMR）诊断。

方法

我们报告了将使用分子显微镜诊断系统进行的组织基因表达检测纳入疑似TCMR的肾移植活检管理中。患者（N = 209）根据诊断和TCMR治疗（使用大剂量类固醇和/或抗胸腺细胞球蛋白）分为3组：第1组：未治疗的组织学TCMR且分子静止（H+M-）；第2组：治疗后的组织学和分子TCMR（H+M+）；第3组：对照组，无组织学或分子（H-M-）排斥反应。

结果

活检时，H+M+组（N = 35；33±22 mL/min/1.73 m²）和H+M-组（N = 30；40±18 mL/min/1.73 m²）的估计肾小球滤过率较差（P = 0.006）；与H-M-组（N = 144；47±24 mL/min/1.73 m²）相比。在H+M-活检中，平均分子急性肾损伤评分（0.33对0.10；P = 0.03）高于H-M-组；而分子TCMR低于H+M+组（0.04对0.54；P < 0.001）。活检后12个月时，H+M+组（38±22 mL/min/1.73 m²）的估计肾小球滤过率仍然较低（P < 0.001），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。在首次活检后的平均随访2.1±1.2年时，H+M+组的死亡审查移植物存活率（74%）低于H+M-组（90%）和H-M-组（92%；P = 0.001）。H+M+病例在随访活检时的排斥反应发生率（20%）在数值上高于H+M-组（7%）（P = 0.12），且新发供体特异性抗体形成情况（H+M+ 24%；H+M- 10%；P = 0.13）。