Autoimmun Rev. 2011 Jun;10(8):503-8. doi: 10.1016/j.autrev.2011.03.001. Epub 2011 Mar 22.
Autoantibodies to intracellular antigens form a large family of immunoglobulins directed to a variety of ubiquitously expressed intracellular molecules, including numerous enzymes, some ribonucleoproteins and double-stranded DNA. These anti-self antibodies have been found to be selectively expressed in sera of patients with several systemic (non-organ-specific) autoimmune diseases, such as systemic sclerosis (SSc), SLE, mixed connective tissue disease, Sjögren's syndrome and idiopathic myopathies. Despite their important diagnostic and prognostic value and their utility in assessing disease activity, little is known about the molecular mechanisms involved in their generation and role in autoimmune diseases nor is it known why particular autoantibodies are preferentially expressed in certain diseases. Here, we review the different lines of research which are presently being conducted to understand how these autoantibodies are generated (e.g. through apoptotic body formation, molecular mimicry and other mechanisms) and how they encounter antigen in order to cause an autoimmune disease. The recently reported mechanism of intracellular immunity mediated by Ro52 (or tripartite motif containing 21, TRIM21) in a cellular model of adenovirus infection is opening new perspectives for studying the effects of autoantibodies once they get inside cells.
自身抗体针对细胞内抗原形成了一大类免疫球蛋白家族，这些免疫球蛋白针对的是广泛表达的各种细胞内分子，包括许多酶、一些核糖核蛋白和双链 DNA。这些抗自身抗体已被发现选择性地表达在几种系统性（非器官特异性）自身免疫性疾病患者的血清中，如系统性硬皮病（SSc）、系统性红斑狼疮（SLE）、混合性结缔组织病、干燥综合征和特发性肌病。尽管它们具有重要的诊断和预后价值，并且在评估疾病活动方面具有实用性，但对于它们的产生的分子机制及其在自身免疫性疾病中的作用知之甚少，也不知道为什么某些自身抗体优先在某些疾病中表达。在这里，我们综述了目前正在进行的不同研究方向，以了解这些自身抗体是如何产生的（例如通过凋亡小体形成、分子模拟和其他机制），以及它们如何遇到抗原从而导致自身免疫性疾病。最近在腺病毒感染的细胞模型中报道的 Ro52（或三结构域蛋白 21，TRIM21）介导的细胞内免疫机制为研究自身抗体进入细胞后的影响开辟了新的视角。
