Aibara Nozomi, Ohyama Kaname, Hidaka Masaaki, Kishikawa Naoya, Miyata Yasuyoshi, Takatsuki Mitsuhisa, Eguchi Susumu, Kuroda Naotaka
Graduate School of Biomedical Sciences, Nagasaki University, Japan.
Graduate School of Biomedical Sciences, Nagasaki University, Japan.
Transpl Immunol. 2018 Jun;48:60-64. doi: 10.1016/j.trim.2018.02.011. Epub 2018 Mar 2.
Liver transplantation is a life-saving procedure for many end-stage liver diseases; however, rejection after transplantation is still occurs in some recipients. The most common form of rejection is T cell-related acute cellular rejection (ACR). To understand the mechanism of rejection, it is necessary to identify immune targets. Since the development of B cell immunity depends upon concordant T cell immunity, we hypothesized that rejection-specific antigens in circulating immune complexes (CICs) may be present in the sera of recipients experiencing rejection, and as such, may be useful as diagnostic biomarkers for ACR. The purpose of this study was to investigate rejection-specific antigens in CICs (CIC-antigens) in serum of ACR patients. We applied immune complexome analysis, in which CICs are separated from whole serum and then subjected to direct tryptic digestion and identification of CIC-antigens by nano-liquid chromatography-tandem mass spectrometry, to sera of 32 living donor liver transplant recipients (10 recipients experienced ACR and the others did not experience). CIC-antigens were compared between rejection and non-rejection groups to elucidate those that were only detected in the rejection group. We identified 11 CIC-antigens that were only detected in patients who experienced rejection, 4 of which (thrombospondin-1, apolipoprotein E, apolipoprotein C-III, and complement factor H) were only detected during ACR.
肝移植是许多终末期肝病的一种挽救生命的治疗方法；然而，移植后仍有一些受者会发生排斥反应。最常见的排斥反应形式是与T细胞相关的急性细胞排斥反应（ACR）。为了了解排斥反应的机制，有必要确定免疫靶点。由于B细胞免疫的发展依赖于协调一致的T细胞免疫，我们推测循环免疫复合物（CICs）中的排斥特异性抗原可能存在于发生排斥反应的受者血清中，因此可能作为ACR的诊断生物标志物。本研究的目的是调查ACR患者血清中CICs中的排斥特异性抗原（CIC抗原）。我们应用免疫复合物组分析，即从全血清中分离出CICs，然后进行直接胰蛋白酶消化，并通过纳升液相色谱-串联质谱法鉴定CIC抗原，对32例活体供肝移植受者（10例发生ACR，其余未发生）的血清进行检测。比较排斥组和非排斥组的CIC抗原，以阐明那些仅在排斥组中检测到的抗原。我们鉴定出11种仅在发生排斥反应的患者中检测到的CIC抗原，其中4种（血小板反应蛋白-1、载脂蛋白E、载脂蛋白C-III和补体因子H）仅在ACR期间检测到。
