PDF(Pubmed)
Abstract：
Acute mixed cellular and antibody-mediated rejection (MR) has an estimated prevalence of 7.8%. However, knowledge of MR immune pathogenesis in cardiac graft rejection remains sparse. We report a case of acute MR in a heart transplant patient with a mutation in the MYH7 gene encoding the protein β-myosin heavy chain, resulting in familial hypertrophic cardiomyopathy. The patient presented with substantial eosinophilic infiltration and extensive production of Human Leukocyte Antigen (HLA)-antibodies associated with shared epitopes. Eosinophilic infiltration in the endo- and myocardium was diagnosed in routine post-transplant biopsies stained with hematoxylin-eosin on day 6 after transplantation. On day 27, the patient presented with dyspnea, weight gain, increased pro-brain natriuretic peptide, and was hospitalized due to suspected acute rejection. Endomyocardial biopsies showed eosinophils in endo- and myocardium with additional lymphocytes and hyperplastic endothelium. Immunohistochemistry, including CD31/CD68 double stain confirmed endothelium-associated macrophages in capillaries and severe C4d positivity in the capillaries and endocardial endothelium. Lymphocytes were identified as primarily CD45+/CD3+ T cells with a concomitant few CD45+/CD20+ B cells. HLA-antibody analysis demonstrated a significant increase in 13 HLA-antibodies present in pre-transplant-serum, of which anti-B7 was donor-specific, and 23 strong de-novo HLA-class I antibodies of which anti-B62 was donor-specific. 72% of HLA-antibodies, including the two donor-specific antibodies, shared the same HLA antigen epitope; 43P+69A or 163L+167W. This is a case reporting both HLA-antibody and pathohistological data indicating the need for better understanding of interactions between cellular and antibody-mediated immune response mechanisms in graft rejection, and the significance of pre-transplant donor-specific antibodies during immunological pre-transplant risk assessment.
摘要：
急性混合细胞和抗体介导的排斥（MR）的患病率估计为7.8％。然而,心脏移植物排斥反应中MR免疫发病机制的知识仍然很少。我们报告了一例心脏移植患者的急性MR病例，该患者的MYH7基因突变编码蛋白β-肌球蛋白重链，导致家族性肥厚型心肌病。患者呈现大量嗜酸性粒细胞浸润和与共有表位相关的人白细胞抗原(HLA)抗体的大量产生。在移植后第6天用苏木精-伊红染色的常规移植后活检中诊断出心肌和心肌中的嗜酸性粒细胞浸润。在第27天，患者出现呼吸困难，体重增加,脑钠肽前体增加，并因怀疑急性排斥而住院。心内膜活检显示心肌和心肌中的嗜酸性粒细胞以及其他淋巴细胞和增生性内皮。免疫组织化学,包括CD31/CD68双重染色证实了毛细血管中的内皮相关巨噬细胞以及毛细血管和心内膜内皮中的严重C4d阳性。淋巴细胞被鉴定为主要是CD45+/CD3+T细胞,伴随少量CD45+/CD20+B细胞。HLA抗体分析表明，移植前血清中存在的13种HLA抗体显着增加，其中抗B7是供体特异性的，和23个抗B62是供体特异性的强从头HLA-I类抗体。72%的HLA抗体,包括两种供体特异性抗体，共有相同的HLA抗原表位;43P+69A或163L+167W。此病例同时报告HLA抗体和病理组织学数据，表明需要更好地了解移植物排斥反应中细胞和抗体介导的免疫应答机制之间的相互作用。以及移植前供体特异性抗体在移植前免疫风险评估中的意义。
