Ohyama Kaname
Graduate School of Biomedical Sciences, Nagasaki University.
Yakugaku Zasshi. 2016;136(2):157-61. doi: 10.1248/yakushi.15-00226-3.
Our immune system resembles an intelligent security system, which continually monitors for foreign invaders (infectious diseases); however, in some cases, this system recognizes healthy parts as something harmful or foreign and then attacks them (autoimmune diseases). The defining characteristics of an autoimmune disease are the existence of T- and B-cell autoreactivity against self proteins (autoantigens). In addition to autoimmune diseases, aberrant host proteins that occur during a certain state of diseases (e.g., cancer) can be recognized as an autoantigen. Immune complexes (ICs) are produced during an immune response and may reflect some aspects of an ongoing immune response. Therefore, the identity of antigens incorporated into ICs provides the information that in the future may aid in the development of diagnosis and treatment strategies for autoimmune diseases, infection, cancer, and transplantation therapy, and this information might be more relevant than information on free antigens. We developed a novel proteomic strategy (immune complexome analysis) in which ICs are separated from serum, followed by direct tryptic digestion and nano-liquid chromatography-tandem mass spectrometry for the identification and profiling of antigens in circulating ICs. We applied this strategy to the analysis of circulating ICs in autoimmune diseases (rheumatoid arthritis, anti-neutrophil cytoplasmic antibody-associated vasculitis, Takayasu's arteritis, mixed connective tissue disease, dermatomyositis, Sjögren's syndrome, systemic scleroderma, and systemic lupus erythematosus), infectious diseases and cancers. In this review, we mainly discuss the results for autoimmune diseases.
我们的免疫系统类似于一个智能安全系统，它不断监测外来入侵者（传染病）；然而，在某些情况下，这个系统会将健康组织识别为有害或外来的东西，然后对其发起攻击（自身免疫性疾病）。自身免疫性疾病的决定性特征是存在针对自身蛋白质（自身抗原）的T细胞和B细胞自身反应性。除了自身免疫性疾病外，在疾病的特定状态（如癌症）期间出现的异常宿主蛋白质也可被识别为自身抗原。免疫复合物（ICs）在免疫反应过程中产生，可能反映正在进行的免疫反应的某些方面。因此，纳入ICs的抗原的身份提供了未来可能有助于自身免疫性疾病、感染、癌症和移植治疗的诊断和治疗策略发展的信息，并且这些信息可能比游离抗原的信息更具相关性。我们开发了一种新的蛋白质组学策略（免疫复合物组分析），其中将ICs从血清中分离出来，然后进行直接胰蛋白酶消化和纳升液相色谱-串联质谱分析，以鉴定和分析循环ICs中的抗原。我们将这种策略应用于自身免疫性疾病（类风湿性关节炎、抗中性粒细胞胞浆抗体相关血管炎、大动脉炎、混合性结缔组织病、皮肌炎、干燥综合征、系统性硬化症和系统性红斑狼疮）、传染病和癌症中循环ICs的分析。在这篇综述中，我们主要讨论自身免疫性疾病的结果。
