Yoshimi Ryusuke, Ishigatsubo Yoshiaki, Ozato Keiko
Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Int J Rheumatol. 2012;2012:718237. doi: 10.1155/2012/718237. Epub 2012 Jun 4.
Systemic lupus erythematosus (SLE) is a chronic, systemic, and autoimmune disease, whose etiology is still unknown. Although there has been progress in the treatment of SLE through the use of glucocorticoid and immunosuppressive drugs, these drugs have limited efficacy and pose significant risks of toxicity. Moreover, prognosis of patients with SLE has remained difficult to assess. TRIM21/Ro52/SS-A1, a 52-kDa protein, is an autoantigen recognized by antibodies in sera of patients with SLE and Sjögren's syndrome (SS), another systemic autoimmune disease, and anti-TRIM21 antibodies have been used as a diagnostic marker for decades. TRIM21 belongs to the tripartite motif-containing (TRIM) super family, which has been found to play important roles in innate and acquired immunity. Recently, TRIM21 has been shown to be involved in both physiological immune responses and pathological autoimmune processes. For example, TRIM21 ubiquitylates proteins of the interferon-regulatory factor (IRF) family and regulates type I interferon and proinflammatory cytokines. In this paper, we summarize molecular features of TRIM21 revealed so far and discuss its potential as an attractive therapeutic target for SLE.
系统性红斑狼疮(SLE)是一种慢性、全身性自身免疫性疾病,其病因尚不清楚。尽管通过使用糖皮质激素和免疫抑制药物在SLE治疗方面取得了进展,但这些药物疗效有限且存在显著的毒性风险。此外,SLE患者的预后仍然难以评估。TRIM21/Ro52/SS-A1是一种52 kDa的蛋白质,是SLE患者以及另一种全身性自身免疫性疾病干燥综合征(SS)患者血清中抗体所识别的自身抗原,抗TRIM21抗体已被用作诊断标志物数十年。TRIM21属于含三联基序(TRIM)超家族,已发现其在先天性和获得性免疫中发挥重要作用。最近,TRIM21已被证明参与生理免疫反应和病理性自身免疫过程。例如,TRIM21使干扰素调节因子(IRF)家族的蛋白质泛素化,并调节I型干扰素和促炎细胞因子。在本文中,我们总结了迄今为止所揭示的TRIM21的分子特征,并讨论了其作为SLE有吸引力的治疗靶点的潜力。