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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Immunoproteomic Analysis of Potentially Severe Non-Graft-Versus-Host Disease Hepatitis After Allogenic Bone Marrow Transplantation
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Immunoproteomic Analysis of Potentially Severe Non-Graft-Versus-Host Disease Hepatitis After Allogenic Bone Marrow Transplantation

机译：同种异体骨髓移植后可能严重的非移植物抗宿主病毒性肝炎的免疫免疫组学分析

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摘要

The development of potentially severe non-graft-versus-host disease (GVHD) hepatitis resembling autoimmune hepatitis (AIH) has been reported after bone marrow transplantation (BMT). The aim of this study was to better characterize this form of hepatitis, particularly through the identification of autoantigens recognized by patient sera. Five patients who received an allogeneic BMT for the treatment of hematological diseases developed liver dysfunction with histological features suggestive of AIH. Before and during the onset of hepatic dysfunction, sera were tested on immunoblottings performed with cytosolic, microsomal, mitochondrial, and nuclear proteins from rat liver homogenate and resolved by two-dimensional electrophoresis. Antigenic targets were identified by mass spectrometry. During the year that followed BMT, all patients presented with GVHD. Acute hepatitis then occurred after the withdrawal, or during the tapering, of immunosuppressive therapy. At that time, no patients had a history of liver toxic drug absorption, patent viral infection, or any histopathological findings consistent with GVHD. Immunoreactive spots stained by sera collected at the time of hepatic dysfunction were more numerous and more intensely expressed than those stained by sera collected before. Considerable patient-dependent pattern heterogeneity was observed. Among the 259 spots stained exclusively by sera collected at the time of hepatitis, a total of 240 spots were identified, corresponding to 103 different proteins. Twelve of them were recognized by sera from 3 patients. Conclusions: This is the first immunological description of potentially severe non-GVHD hepatitis occurring after BMT, determined using a proteomic approach and enabling a discussion of the mechanisms that transform an alloimmune reaction into an autoimmune response. Any decision to withdraw immunosuppression after allogeneic BMT should be made with caution.
机译：骨髓移植（BMT）后，已经报道了潜在的严重非移植物抗宿主病（GVHD）肝炎，类似于自身免疫性肝炎（AIH）。这项研究的目的是更好地表征这种肝炎，特别是通过鉴定患者血清识别的自身抗原。五名接受同种异体BMT治疗血液疾病的患者出现肝功能障碍，其组织学特征提示AIH。在肝功能异常发作之前和期间，对血清进行了免疫印迹试验，用来自大鼠肝脏的细胞质，微粒体，线粒体和核蛋白匀浆并通过二维电泳进行了免疫印迹分析。通过质谱鉴定抗原靶标。在BMT之后的一年中，所有患者均出现了GVHD。急性肝炎然后在免疫抑制治疗停药后或逐渐减少期间发生。当时，没有患者有肝毒性药物吸收史，病毒性感染或任何与GVHD一致的组织病理学发现。与之前收集的血清染色相比，被肝功能障碍时收集的血清染色的免疫反应斑点数量更多，表达更强烈。观察到相当多的患者依赖性模式异质性。在肝炎时收集的仅被血清染色的259个斑点中，总共鉴定出240个斑点，对应于103种不同的蛋白质。其中有12例被3例患者的血清所识别。结论：这是使用蛋白质组学方法确定的BMT后发生的潜在严重非GVHD肝炎的首次免疫学描述，并能够讨论将同种免疫反应转化为自身免疫反应的机制。异基因BMT后撤回免疫抑制的任何决定均应谨慎。

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