A plot of PON1 TF values shows reduced plasma PON1 levels were observed for 5 out of the 10 indepen dent twin pair control sample sets irrespective of disease diagnosis. A calculation of the mean reduction in PON1 levels among the 10 pairs of dis ease discordant twins was similar in both protein blot and proteomics analyses. A similar protein blot analysis of the RBP1 this marker whose plasma levels were elevated in SAID affected twins in comparisons with either unaffected twins or unrelated controls is shown in Figure 5C. Normalized plasma RBP1 levels were increased approximately 1. 2 fold in affected twins compared to unaffected twins or unrelated controls. A comparable increase of plasma RBP1 was detected in the proteomics analysis.

We did not, however, detect elevated levels of LRG1 in SAID affected twins Inhibitors,Modulators,Libraries by protein blot analysis in contrast to the approximately 1. 4 fold increase observed by plasma proteomics. Discussion While certain autoimmune diseases share selected genetic, Inhibitors,Modulators,Libraries clinical and laboratory features, it is not clear if In the present study, we have evaluated biologic path ways altered among multiple SAID by studying levels of plasma proteins using LC ESI MS from MZ twins dis cordant for SAID and unrelated, matched controls. Blood plasma is well suited to the study of systemic or multi organ diseases given its capacity to sample pro teins from damaged tissues and detect changes in other physiologic pathways associated with complex host responses to disease processes and infectious and or other environmental agents.

The human plasma proteome is one of the most complex and better charac terized human bio fluids wherein the identity and expression levels of its approximately 1,000 distinct pro tein constituents are currently cataloged. Previous studies have examined human tissue and Inhibitors,Modulators,Libraries bio fluid proteomes in autoimmune conditions with the Inhibitors,Modulators,Libraries goal of identifying disease specific biomarkers to aid in improved disease diagnosis and understanding of under lying Inhibitors,Modulators,Libraries pathogeneses. These findings point con sistently to coordinated changes in the levels of multiple proteins involved in such canonical pathways as immune activation, signal transduction, cell adhesion, apoptosis, and acute phase responses, in addition to various tran scription factors, structural and transport proteins.

In fact, composite phenotypic profiles of coordinated changes in multiple protein factors and physiologic pathways rather than solitary biomarkers may prove more reliable nearly in differentiating complex and sometimes overlapping autoimmune syndromes. We examined multiple SAID in an attempt to uncover shared biomarkers or proteomic profiles, with the under standing that these otherwise heterogeneous disorders often share many clinical features, immunologic abnorm alities, genetic risk factors and serum autoantibodies.