Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil.
Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil ; Department of Genetics, Federal University of Pernambuco, Recife, Pernambuco, Brazil.
Curr Genomics. 2014 Feb;15(1):52-65. doi: 10.2174/138920291501140306113715.
Systemic Lupus Erythematosus (SLE) is one of the most relevant world-wide autoimmune disorders. The formation of autoantibodies and the deposition of antibody-containing immune complexes in blood vessels throughout the body is the main pathogenic mechanism of SLE leading to heterogeneous clinical manifestations and target tissue damage. The complexity of etiology and pathogenesis in SLE, enclosing genetic and environmental factors, apparently is one of the greatest challenges for both researchers and clinicians. Strong indications for a genetic background in SLE come from studies in families as well as in monozygotic and dizygotic twins, discovering several SLE-associated loci and genes (e.g. IRF5, PTPN22, CTLA4, STAT4 and BANK1). As SLE has a complex genetic background, none of these genes is likely to be entirely responsible for triggering autoimmune response in SLE even if they disclosure a potentially novel molecular mechanisms in the pathogenesis' disease. The clinical manifestations and disease severity varies greatly among patients, thus several studies try to associate clinical heterogeneity and prognosis with specific genetic polymorphisms in SLE associated genes. The continue effort to describe new predisposing or modulating genes in SLE is justified by the limited knowledge about the pathogenesis, assorted clinical manifestation and the possible prevention strategies. In this review we describe newly discovered, as well as the most studied genes associated to SLE susceptibility, and relate them to clinical manifestations of the disease.
系统性红斑狼疮（SLE）是全球最相关的自身免疫性疾病之一。自身抗体的形成和含有抗体的免疫复合物在全身血管中的沉积是导致 SLE 异质临床表现和靶组织损伤的主要致病机制。SLE 的病因和发病机制的复杂性，包括遗传和环境因素，显然是研究人员和临床医生面临的最大挑战之一。来自家族、同卵双胞胎和异卵双胞胎研究的强烈提示表明 SLE 具有遗传背景，发现了几个与 SLE 相关的基因座和基因（例如 IRF5、PTPN22、CTLA4、STAT4 和 BANK1）。由于 SLE 具有复杂的遗传背景，即使这些基因揭示了发病机制疾病中的潜在新分子机制，也不太可能完全导致 SLE 自身免疫反应的触发。患者之间的临床表现和疾病严重程度差异很大，因此一些研究试图将临床异质性和预后与 SLE 相关基因的特定遗传多态性联系起来。由于对发病机制、各种临床表现和可能的预防策略的了解有限，因此继续努力描述 SLE 中易感性的新潜在或调节基因是合理的。在这篇综述中，我们描述了新发现的以及研究最多的与 SLE 易感性相关的基因，并将它们与疾病的临床表现联系起来。
