Proteomic analyses of human biological fluids have enabled the differential quantitation of large numbers of protein Calcitriol molecules Inhibitors,Modulators,Libraries between healthy and diseased subjects. Studies utilizing bio fluid proteomics have identified multiple, pathologic markers and mole cular pathways associated with different disease pheno types, Inhibitors,Modulators,Libraries severities, and therapeutic responses. Yet, despite these in roads, considerable variability in the published SAID literature exists and likely results from multiple factors including different proteomic methodol ogies, choice of bio fluids or tissues analyzed, and the inherent heterogeneity of SAID phe notypes, patient histories, and human genetic variations. Nevertheless, some consensus has emerged in multiple, independent lines of proteomic research in the rheu matic diseases.

These common findings in multiple rheumatic diseases to date include Type I interferon inducible proteins, autoantibodies, numerous inflamma Inhibitors,Modulators,Libraries tory cytokines chemokines, and markers of molecular pathways associated with chronic immune activation, oxidative stress, coagulation, protein degradation and lipid metabolism. Proteomic analysis of blood plasma has several useful research advantages Inhibitors,Modulators,Libraries despite its technical complexity. Blood plasma has an exceedingly complex proteome consisting of approximately 1,000 distinct polypeptides, whose concentrations vary over several orders of magni tude. The vast majority of total plasma protein, how ever, is comprised of a smaller number of more abundant proteins, which necessitate their pre depletion to enhance the detection of other minor pro tein constituents present at much lower concentrations.

Inhibitors,Modulators,Libraries Despite these methodologic challenges, the plasma pro teome is one of the most extensively characterized bio fluids in humans. Moreover, plasma samples are more 17-DMAG Phase 2 easily obtained using a minimally invasive proce dure, and are an ideal source of circulating disease asso ciated markers as well as those derived from dead or leaking cells from pathologic tissues throughout the body. In human proteomic studies, statistically significant differences in protein levels among experimental and control subjects are often subtle and influenced potenlially by the degree of genetic variation that exists among human study sub jects. To help mitigate the potentially confound ing effects of human genetic polymorphisms in our study population, we utilized liquid chromatography electrospray ionization mass spectrometry to measure quantitative differences in the plasma pro teome of SAID discordant MZ twins and unrelated, matched controls.