Petrohai Agnes, Nagy Gergely, Bosze Szilvia, Hudecz Ferenc, Zsiros Emese, Paragh György, Nyárády Zoltán, Németh Péter, Berki Timea
Department of Cardiovascular Surgery, Semmelweis University, Városmajor út 68, 1122, Budapest, Hungary.
Transpl Int. 2005 May;17(12):834-40. doi: 10.1007/s00147-004-0794-4. Epub 2005 Feb 15.
Autoimmune mechanisms play an important role in the pathogenesis of allograft vasculopathy following heart transplantation, but the autoantigens involved have been only sparsely studied. Citrate synthase (CS) enzyme is a conserved molecule, and, as an important mitochondrial autoantigen, it is protected by the "immunological homunculus". Tissue destruction and alteration of the immune regulatory mechanisms can induce pathological immune response against CS in other autoimmune diseases. In our present study we aimed to detect CS-specific autoantibodies in heart transplant patients, therefore, prospective, randomised clinical tests were conducted on 33 heart transplant patients and compared with 130 healthy blood donors. The level and isotype of CS antibodies were detected by simple binding indirect enzyme-linked immunosorbent assay (ELISA). The epitope specificities of the autoantibodies were measured on synthetic overlapping peptide sequences of CS enzyme by an indirect multi-pin ELISA method. Mainly IgM isotype CS autoantibodies were found in healthy controls, while IgG was found at higher levels and frequency (four-times higher) in heart transplant patients. Autoantibodies of IgG isotype recognise different epitopes than do autoantibodies of IgM isotype, even within the same group and individual. New epitope-specific IgG and IgM isotype autoantibodies appeared in heart transplant patients when compared with the controls. Our findings suggest a possible role of CS-specific autoantibodies in the pathomechanism of allograft vasculopathy.
自身免疫机制在心脏移植后同种异体血管病变的发病机制中起重要作用，但对相关自身抗原的研究却很少。柠檬酸合酶（CS）是一种保守分子，作为重要的线粒体自身抗原，它受到“免疫小体”的保护。在其他自身免疫性疾病中，组织破坏和免疫调节机制的改变可诱导针对CS的病理性免疫反应。在我们目前的研究中，我们旨在检测心脏移植患者中CS特异性自身抗体，因此，对33名心脏移植患者进行了前瞻性随机临床试验，并与130名健康献血者进行了比较。通过简单结合间接酶联免疫吸附测定（ELISA）检测CS抗体的水平和亚型。通过间接多针ELISA方法在CS酶的合成重叠肽序列上测定自身抗体的表位特异性。在健康对照中主要发现IgM亚型的CS自身抗体，而在心脏移植患者中发现IgG水平和频率更高（高四倍）。即使在同一组和个体中，IgG亚型的自身抗体与IgM亚型的自身抗体识别不同的表位。与对照组相比，心脏移植患者中出现了新的表位特异性IgG和IgM亚型自身抗体。我们的研究结果表明CS特异性自身抗体在同种异体血管病变的发病机制中可能起作用。
