Current status and progress on antibody-mediated rejection in heart transplantation

doi:10.3877/cma.j.issn.1674-3903.2022.05.002

Abstract

Abstract:

Antibody-mediated rejection (AMR) is proved to be a crucial complication in heart transplantation, which has not been well evaluated and studied in China. Nowadays, it is considered that AMR contains a series of evolution process from pathological changes to clinic manifestation, which starts with the accumulation of immune factors (such as antibody, complement), the activation of complement and ends with graft tissues injury. Clinically, AMR was classified as circulating antibody silent stage, sub-clinical stage and symptomatic AMR stage. The mechanism of AMR involved in an inflammatory reaction induced by deposition of immunoglobulins and complements within the microvessels of the grafts, in which the activation of complements played a core role. Therefore, immunological assay of C4d and C3d in endomyocardial biopsy specimens combined with evidence of histopathology capillaries injury were necessary for the diagnosis of AMR. While noninvasive gene detection with Allomap and donor-derived cell-free DNA were effective method serving as screening and monitoring AMR. Recommendations on management of AMR consisted a combination of corticosteroid, intravenous immune globulin, plasmapheresis or rituximab by scale of AMR, which were proven to be effective against immune injury. However, the efficacy of anti-CD52 monoclonal antibody, eculizumab and photochemotherapy remains to be further evaluated.

Key words: Cardiac transplantation, Antibody-mediated rejection, Acute cellular rejection, Cardiac allograft vasculopathy, Treatment

Shouguo Yang. Current status and progress on antibody-mediated rejection in heart transplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2022, 16(05): 266-276.

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URL: https://zhyzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3903.2022.05.002

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References 52

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1990年版		2004年版
分级	依据	分级	依据
AMR 0级	无组织损害证据	无AMR	无AMR的组织病理学改变或免疫病理学改变
AMR 1级	体液性排斥反应，免疫荧光阳性，血管炎或在无细胞浸润情况下的严重组织水肿	AMR阳性	AMR组织病理学证据阳性；免疫荧光(C3d和/或C4d)阳性或免疫过氧化物酶染色(CD68/C4d)阳性

1990年版		2004年版
分级	依据	分级	依据
AMR 0级	无组织损害证据	无AMR	无AMR的组织病理学改变或免疫病理学改变
AMR 1级	体液性排斥反应，免疫荧光阳性，血管炎或在无细胞浸润情况下的严重组织水肿	AMR阳性	AMR组织病理学证据阳性；免疫荧光(C3d和/或C4d)阳性或免疫过氧化物酶染色(CD68/C4d)阳性

标志物	免疫学意义	AMR中的可检测性	局限性
IgG/IgM	免疫球蛋白结合	+	容易解离，半衰期短，不同研究者评估有差异
C3/C1q	补体活化	+	半衰期短
C3d/C4d	补体活化	+	半衰期长，二者联合检测诊断AMR更具价值
HLA-DR	血管内皮完整性	+	染色多数阳性，但断裂模式代表血管损伤
纤维蛋白	血栓环境	+	间质渗出提示严重AMR
CD55/CD59	补体抑制因子	－	需长时间孵化和颗粒染色模式
CD31/CD34/CD68	血管内巨噬细胞	+	CD68可用于确认单核细胞的巨噬细胞谱系；CD31/CD34是内皮细胞的标记，用于标记并区别巨噬细胞在血管内的定位

标志物	免疫学意义	AMR中的可检测性	局限性
IgG/IgM	免疫球蛋白结合	+	容易解离，半衰期短，不同研究者评估有差异
C3/C1q	补体活化	+	半衰期短
C3d/C4d	补体活化	+	半衰期长，二者联合检测诊断AMR更具价值
HLA-DR	血管内皮完整性	+	染色多数阳性，但断裂模式代表血管损伤
纤维蛋白	血栓环境	+	间质渗出提示严重AMR
CD55/CD59	补体抑制因子	－	需长时间孵化和颗粒染色模式
CD31/CD34/CD68	血管内巨噬细胞	+	CD68可用于确认单核细胞的巨噬细胞谱系；CD31/CD34是内皮细胞的标记，用于标记并区别巨噬细胞在血管内的定位

	必需条件	可选条件
免疫病理学证据：抗体介导的损伤(a，b，c任一项)	a.免疫荧光检测：C3d和/或C4d或C1q(++~+++)；同时合并IgG、IgM和/或IgA阳性 b.免疫组织化学：毛细血管内CD68阳性和/或毛细血管C4d(++~+++) c.血管内存在纤维蛋白(重度)	无
组织病理学证据：急性毛细血管损伤(a和b同时具备)	a.毛细血管内皮水肿 b.毛细血管内巨噬细胞	c.毛细血管内中性粒细胞(重度) d.间质水肿或出血(重度)
临床证据：移植物功能障碍	－	临床症状、血流动力学指标异常或超声心动图LVEF降低
血清抗体证据	－	HLA抗体或非HLA抗体阳性

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