Luppi P, Alexander A, Bertera S, Noonan K, Trucco M
Department of Pediatrics, University of Pittsburgh School of Medicine, Rangos Research Center, Children's Hospital of Pittsburgh, Pennsylvania, USA.
J Biol Regul Homeost Agents. 1999 Jan-Mar;13(1):14-26.
An important characteristic of autoimmune diseases is their association with major histocompatibility complex class I and class II alleles. In this study, we compared insulin-dependent diabetes mellitus (IDDM) with idiopathic dilated cardiomyopathy (IDC) from a strictly immunologic perspective. Although the target organs are different, being in one case the insulin-producing beta cells of the pancreas and in the other case the myocytes of the heart, many aspects of the tissue-specific immune destruction are common. Similar yet different Coxsackievirus B strains with either pancreotropic or cardiotropic specificity are able to perpetrate the first injury of the respective target tissue. Their shared capacity of inducing a superantigenic reaction further enhances the damage. Once previously secluded autoantigens are then exposed to the immune system, the tissue injury is completed via a more conventional type of immune response. On the basis of the compounded results we obtained, it is possible to propose that the same HLA-DQ molecules which are able to protect the individuals from IDDM (e.g., HLA-DQA10102, DQB10602) seem to favour the enteroviral attack to the myocardium, while alleles which confer the strongest susceptibility to IDDM (e.g., DQA10301, DQB10302), seem unable to sustain the immune attack against the heart.
自身免疫性疾病的一个重要特征是它们与主要组织相容性复合体I类和II类等位基因相关。在本研究中，我们从严格的免疫学角度比较了胰岛素依赖型糖尿病（IDDM）和特发性扩张型心肌病（IDC）。尽管靶器官不同，一种情况是胰腺中产生胰岛素的β细胞，另一种情况是心脏的心肌细胞，但组织特异性免疫破坏的许多方面是相同的。具有胰腺嗜性或心脏嗜性特异性的相似但不同的柯萨奇病毒B株能够对各自的靶组织造成首次损伤。它们诱导超抗原反应的共同能力进一步加剧了损伤。一旦先前隐蔽的自身抗原随后暴露于免疫系统，组织损伤就会通过更传统的免疫反应类型完成。根据我们获得的综合结果，有可能提出，能够保护个体免受IDDM影响的相同HLA-DQ分子（例如，HLA-DQA10102、DQB10602）似乎有利于肠道病毒对心肌的攻击，而赋予对IDDM最强易感性的等位基因（例如，DQA10301、DQB10302）似乎无法维持对心脏的免疫攻击。
