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供者特异性抗体与慢性活动性抗体介导排斥反应表型的不依从性之间的相关性及其对肾移植存活的影响。

Correlations between donor-specific antibodies and non-adherence with chronic active antibody-mediated rejection phenotypes and their impact on kidney graft survival.

作者信息

Malheiro Jorge, Santos Sofia, Tafulo Sandra, Dias Leonídio, Martins La Salete, Fonseca Isabel, Almeida Manuela, Pedroso Sofia, Beirão Idalina, Castro-Henriques António, Cabrita António

机构信息

Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.

Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Portugal.

出版信息

Hum Immunol. 2018 Jun;79(6):413-423. doi: 10.1016/j.humimm.2018.03.004. Epub 2018 Mar 22.

Abstract

Chronic-active antibody-mediated rejection (CAABMR) is associated with poor kidney graft survival and has no clear effective treatment. Forty-one cases of CAABMR were detected in indication graft biopsies and evaluated according to current Banff classification. We investigated the impact of concurrent donor-specific antibodies (DSA) and their characteristics, together with non-adherence regarding immunosuppression on CAABMR histopathological phenotypes and prognosis. Twenty-four (59%) patients had detectable DSA at biopsy, with 15 of them being considered non-adherent. Graft function at biopsy was similar in DSA (+) and (-) patients. DSA (+) patients had significantly higher tubulointerstitial inflammation (i and ti) and acute humoral (g+ptc+v+C4d) composite score than DSA (-). DSA (+)/non-adherent cases presented additionally with increased microvascular inflammation (ptc and v), besides having a distinctively lower ah score. C1q DSA strength was higher (P = .046) in non-adherent patients and correlated closely with C4d score (P = .002). Lower graft function and ah score, higher proteinuria and ci + ct score, and, separately per each model, DSA (+) (HR = 2.446, P = .034), DSA (+)/non-adherent (HR = 3.657, P = .005) and DSA (+)/C1q (+) (HR = 4.831, P = .003) status were independent predictors of graft failure. CAABMR with concomitant DSA pose a higher risk of graft failure. Adherence should be evaluated, and histopathological phenotyping and DSA characterization may add critical information.

摘要

慢性活动性抗体介导的排斥反应(CAABMR)与肾移植存活率低相关,且尚无明确有效的治疗方法。在指征性移植肾活检中检测到41例CAABMR,并根据当前的班夫分类法进行评估。我们研究了同时存在的供者特异性抗体(DSA)及其特征,以及免疫抑制不依从对CAABMR组织病理学表型和预后的影响。24例(59%)患者在活检时可检测到DSA,其中15例被认为不依从。DSA阳性和阴性患者活检时的移植肾功能相似。DSA阳性患者的肾小管间质炎症(i和ti)和急性体液性(g+ptc+v+C4d)综合评分显著高于DSA阴性患者。DSA阳性/不依从病例除了具有明显较低的急性体液性评分外,还表现为微血管炎症(ptc和v)增加。非依从患者的C1q DSA强度更高(P = 0.046),且与C4d评分密切相关(P = 0.002)。较低的移植肾功能和急性体液性评分、较高的蛋白尿和ci + ct评分,以及在每个模型中单独的DSA阳性(HR = 2.446,P = 0.034)、DSA阳性/不依从(HR = 3.657,P = 0.005)和DSA阳性/C1q阳性(HR = 4.831,P = 0.003)状态是移植失败的独立预测因素。伴有DSA的CAABMR移植失败风险更高。应评估依从性,组织病理学表型分析和DSA特征分析可能会提供关键信息。

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