Proteomic analysis of circulating immune complexes in juvenile idiopathic arthritis reveals disease-associated proteins
Proteomic analysis of circulating immune complexes in juvenile idiopathic arthritis reveals disease-associated proteins
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DOI：
10.1002/prca.200800073
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发表时间：
2009-07-01
影响因子：
2
通讯作者：
Moore, Terry L.
中科院分区：
文献类型：
--
作者：
Low, Jason M.;Chauhan, Anil K.;Moore, Terry L.
幼年特发性关节炎反映了一组以循环免疫复合物浓度升高为特征的临床异质性关节炎。在这项研究中，循环免疫复合物蛋白质组进行了检查，以阐明疾病相关的蛋白质，在患者的侵略性，有时破坏性，疾病表型过表达。为了解决这个蛋白质组，循环免疫复合物从慢性，糜烂性或早发性，侵袭性疾病的患者的血清中分离，并从医学缓解或健康对照的患者，随后通过2-DE分离蛋白质。与对照组相比，37个蛋白质点在侵袭性疾病组的循环免疫复合物中过表达，其中28个蛋白质点迄今已被确定。其中已鉴定出甘油醛-3-磷酸脱氢酶、血清转铁蛋白和α-1-抗胰蛋白酶的蛋白水解片段。总的来说，这28种推定的疾病相关蛋白质最肯定地有助于免疫复合物的形成，并可能在疾病病因学和发病机制中起重要作用。此外，这些蛋白质代表了侵袭性疾病的标志物，可以帮助诊断和管理策略，以及预防或控制疾病结果的潜在治疗靶点。这是首次对幼年特发性关节炎循环免疫复合物蛋白质组进行深入分析。
juvenile idiopathic arthritis reflects a group of clinically heterogeneous arthritides hallmarked by elevated concentrations of circulating immune complexes. In this study, the circulating immune complex proteome was examined to elucidate disease-associated proteins that are overexpressed in patients with an aggressive, and at times destructive, disease phenotype. To solve this proteome, circulating immune complexes were isolated from the sera of patients with chronic, erosive or early-onset, aggressive disease and from patients in medical remission or healthy controls subsequent to protein separation by 2-DE. Thirty-seven protein spots were overexpressed in the circulating immune complexes of the aggressive disease groups as compared to controls, 28 of which have been confidently identified to date. Proteolytic fragments of glyceraldehyde-3-phosphate dehydrogenase, serotransferrin, and alpha-1-antitrypsin have been identified among others. In total, these 28 putative disease-associated proteins most definitely contribute to immune complex formation and likely have a significant role in disease etiology and pathogenesis. Moreover, these proteins represent markers of aggressive disease, which could aid in diagnosis and management strategies, and potential therapeutic targets to prevent or control disease outcome. This is the first in-depth analysis of the circulating immune complex proteome in juvenile idiopathic arthritis.