Antibody‐mediated rejection (AMR) driven by the development of donor‐specific antibodies (DSA) directed against mismatched donor human leukocyte antigen (HLA) is a major risk factor for graft loss in cardiac transplantation. Recently, the relevance of non‐HLA antibodies has become more prominent as AMR can be diagnosed in the absence of circulating DSA. Here, we assessed a single‐center cohort of 64 orthotopic heart transplant recipients transplanted between 1994 and 2014. Serum collected from patients with ≥ pAMR1 (n = 43) and non‐AMR (n = 21) were tested for reactivity against a panel of 44 non‐HLA autoantigens. The AMR group had a significantly greater percentage of patients with elevated reactivity to autoantigens compared to non‐AMR (P = .002) and healthy controls (n = 94, P < .0001). DSA‐positive AMR patients exhibited greater reactivity to autoantigens compared to DSA‐negative (P < .0001) and AMR patients with DSA and PRA > 10% were identified as the subgroup with significantly elevated responses. Reactivity to 4 antigens, vimentin, beta‐tubulin, lamin A/C, and apolipoprotein L2, was significantly different between AMR and non‐AMR patients. Moreover, increased reactivity to these antigens was associated with graft failure. These results suggest that antibodies to non‐HLA are associated with DSA‐positive AMR although their specific role in mediating allograft injury is not yet understood.

中文翻译：

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分析心脏移植后抗体介导的排斥反应中的非 HLA 抗体反应。

由针对错配的供体人类白细胞抗原 (HLA) 的供体特异性抗体 (DSA) 的发展驱动的抗体介导的排斥反应 (AMR) 是心脏移植移植物丢失的主要危险因素。最近，非 HLA 抗体的相关性变得更加突出，因为可以在没有循环 DSA 的情况下诊断 AMR。在这里，我们评估了 1994 年至 2014 年间移植的 64 名原位心脏移植受者的单中心队列。从 pAMR1 (n = 43) 和非 AMR (n = 21) 患者收集的血清针对一组44 种非 HLA 自身抗原。与非 AMR ( P  = .002) 和健康对照组 (n = 94, P <.0001)。与 DSA 阴性相比，DSA 阳性 AMR 患者对自身抗原表现出更高的反应性 ( P  < .0001)，并且 DSA 和 PRA > 10% 的 AMR 患者被确定为反应显着升高的亚组。AMR 和非 AMR 患者对 4 种抗原（波形蛋白、β-微管蛋白、核纤层蛋白 A/C 和载脂蛋白 L2）的反应性显着不同。此外，对这些抗原的反应性增加与移植失败有关。这些结果表明，非 HLA 抗体与 DSA 阳性 AMR 相关，尽管它们在介导同种异体移植物损伤中的具体作用尚不清楚。