Autoantibodies as predictive and diagnostic markers of idiopathic inflammatory myopathies
Autoantibodies as predictive and diagnostic markers of idiopathic inflammatory myopathies
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DOI：
10.1080/08916930410001710839
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发表时间：
2004-06-01
期刊：
影响因子：
3.5
通讯作者：
Miller, FW
中科院分区：
文献类型：
--
作者：
Sarkar, K;Miller, FW
特发性炎症性肌病(IIM)是一组不同的全身性疾病，以不明原因的慢性肌肉炎症为特征。[1]传统上根据近30年前定义的标准对其进行诊断。[2]这些包括近端对称性肌肉无力、血清肌源性酶水平升高、特征性肌电异常、肌肉活检中慢性炎症的证据，以及在皮肌炎的情况下出现病理性皮疹。IIM是一种罕见的疾病，年发病率为1/10万。三种不同的临床病理亚型包括IIM-多发性肌炎(PM)、皮肌炎(DM)和包涵体肌炎(IBM)。PM和DM患者都会在几周到几个月的时间里缓慢地出现近侧的、通常是对称性的肌肉无力。皮肌炎的特征是病理性皮疹，包括上眼睑的嗜日性皮疹，蓝紫色变色，以及Gottron丘疹，关节和其他伸肌表面可触及的隆起病变。[3]肌肉活检中出现包涵体是IBM的特征。肌炎可单独发生或与其他结缔组织疾病相关，如系统性红斑狼疮(SLE)、类风湿性关节炎(RA)、干燥综合征或系统性硬化症(SSC)。[1，4-8]虽然肌炎的病因尚不清楚，但不同的肌炎亚型可能有不同的发病机制。在肌炎患者的血清中发现了大量的自身抗体，可分为仅在肌炎患者中出现的自身抗体(肌炎特异性自身抗体或MSA)，以及在肌炎患者和其他自身免疫性疾病患者中都可见的自身抗体(肌炎相关自身抗体或MAA)。最近综述了ARS分子及其蛋白分解片段在肌炎启动和维持免疫反应中的有趣作用。[10]除了体液免疫，细胞免疫在这两种疾病中也很突出。我们和其他人对肌炎患者特定临床和血清学分组中T细胞受体(TCR)基因表达的限制模式的研究证实了T细胞在这些免疫疾病中的作用。[11，12]不仅侵袭性炎症细胞，而且靶肌肉细胞可能参与了疾病的发病机制。[13，14]其他提出的致病因素包括促炎细胞因子、趋化因子和黏附分子的表达增加。细胞因子包括IL-1a、IL-1b和转化生长因子-b在PM、DM和IBM患者的肌肉中表达，趋化因子特别是MIP-1a在肌炎患者的靶组织中也普遍存在。溶酶体功能异常和淀粉样蛋白前体蛋白及其蛋白降解片段在老化的细胞内环境中的异常积聚被认为是IBM的关键致病事件。[15，16]遗传危险因素也可能参与肌炎的发病。MHC I类和II类等位基因和各种形式的肌炎和MSA之间的关联是肌炎可能必需的遗传易感性的有力证据。[17]环境风险因素知之甚少，但包括许多感染性和非感染性因素。[18]一个有效的假设是，在遗传易感的宿主中，某些环境因素在肌炎和其他自身免疫性疾病中触发慢性免疫激活和随后的炎症和组织破坏。
The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of systemic diseases characterized by the effects of chronic muscle inflammation of unknown cause.[1] They are traditionally diagnosed by criteria defined nearly three decades ago.[2] These include proximal symmetrical muscle weakness, elevated serum levels of muscle-derived enzymes, characteristic electromyographic abnormalities, evidence of chronic inflammation in the muscle biopsy and, in the case of dermatomyositis, pathognomonic rashes. The IIM are uncommon diseases with an annual incidence of 1 in 100,000. Three distinct clinicopathologic subgroups comprise the IIM—polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM). Both PM and DM patients develop proximal and often symmetrical muscle weakness slowly over weeks to months. Dermatomyositis is characterized by pathognomonic skin rashes, which include the heliotrope rash, a blue-purple discoloration on the upper eyelids, and Gottron’s papules, raised palpable lesions over the knuckles and other extensor surfaces.[3] The presence of inclusion bodies on muscle biopsy is a characteristic feature of IBM. Myositis may occur in an isolated form or in association with other connective tissue diseases, eg systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren’s syndrome, or systemic sclerosis (SSc).[1, 4–8] Though the etiology of myositis remains unclear, it is likely that different pathogeneses are at work in different subsets of myositis. A large number of autoantibodies are found in the sera of myositis patients, which can be divided into those which are only seen in patients with myositis (myositis-specific autoantibodies or MSAs) and those seen in both myositis patients and patients with other autoimmune conditions (myositis-associated autoantibodies or MAAs).[9] The most common MSAs are directed against the aminoacyl tRNA synthetases (ARS). The interesting roles of ARS molecules and their proteolytic fragments in priming and sustaining immune responses in myositis have been reviewed recently.[10] In addition to humoral immunity, cellular immunity is also prominent in both disease. Studies by our group and others on the restricted patterns of T-cell receptor (TCR) gene expression in defined clinical and serological groups of patients with myositis documents the role of T cells in these immune disorders.[11, 12] Not only invading inflammatory cells but also target muscle cells may contribute to the disease pathogenesis.[13, 14] Other proposed pathogenic factors include increased expression of proinflammatory cytokines, chemokines and adhesion molecules. Cytokines including IL-1a, IL-1b and TGF-b are expressed in muscles of PM, DM and IBM patients, and chemokines, especially MIP-1a, are also commonly found in the target tissues of myositis patients. Abnormal lysosomal function and abnormal accumulations of amyloid-b precursor protein and it’s proteolytic fragment within the aging intracellular milieu have been proposed as key pathogenetic events in IBM.[15, 16] Genetic risk factors also likely contribute to the pathogenesis of myositis. Associations among MHC class I and class II alleles and various forms of myositis and MSAs are strong evidence for the genetic predisposition that likely is necessary for myositis.[17] Environmental risk factors are poorly understood but include a number of infectious and noninfectious agents.[18] A working hypothesis is that in a genetically predisposed host, certain environmental factors trigger chronic immune activation and subsequent inflammation and tissue destruction in myositis and other autoimmune diseases.[19, 20]