plasma proteomic profiles from disease-discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases血浆蛋白质组学disease-discordant同卵双胞胎的资料显示,分子途径在多个共享系统性自身免疫性疾病.pdfVIP

O’Hanlon et al. Arthritis Research Therapy 2011, 13:R181 /content/13/6/R181 RESEARCH ARTICLE Open Access Plasma proteomic profiles from disease- discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases* 1* 1 1 2 1 1 Terrance P O’Hanlon , Zhuoyan Li , Lu Gan , Mark F Gourley , Lisa G Rider and Frederick W Miller Abstract Introduction: Although systemic autoimmune diseases (SAID) share many clinical and laboratory features, whether they also share some common features of pathogenesis remains unclear. We assessed plasma proteomic profiles among different SAID for evidence of common molecular pathways that could provide insights into pathogenic mechanisms shared by these diseases. Methods: Differential quantitative proteomic analyses (one-dimensional reverse-phase liquid chromatography-mass spectrometry) were performed to assess patterns of plasma protein expression. Monozygotic twins (four pairs discordant for systemic lupus erythematosus, four pairs discordant for juvenile idiopathic arthritis and two pairs discordant for juvenile dermatomyositis) were studied to minimize polymorphic gene effects. Comparisons were also made to 10 unrelated, matched controls. Results: Multiple plasma proteins, including acute phase reactants, structural proteins, immune response proteins, coagulation and transcriptional factors, were differentially expressed similarly among the different SAID studied. Multivariate Random Forest modeling identified seven proteins whose combined altered expression levels effectively segregated affected vs. unaffected twins. Among these seven proteins, four were also identified in univariate analyses of proteomic data (sy