Malheiro Jorge, Santos Sofia, Tafulo Sandra, Dias Leonídio, Martins La Salete, Fonseca Isabel, Almeida Manuela, Pedroso Sofia, Beirão Idalina, Castro-Henriques António, Cabrita António
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.
Hum Immunol. 2018 Jun;79(6):413-423. doi: 10.1016/j.humimm.2018.03.004. Epub 2018 Mar 22.
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.
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。