earticle

영어

Mechanisms underlying disease pathogenesis are not well understood in the context of common etiological factors such as microbial infection, inflammation, malignancy or tissue breakdown. Such processes may be elucidated by identifying disease-related molecular markers, such as acute phase proteins, cytokines, cytoskeletal fragments and autoantigens. In an attempt to identify such markers, we have developed a novel platform, namely multiple lectin affinity chromatography (M-LAC) to study the plasma glycoproteome in patients and healthy donors in a series of studies ranging from cancer to autoimmune disease. The M-LAC platform allowed the evaluation of changes in concentration of glycoproteins, and to comprehensively survey the plasma proteome. We then used a second method, intact peptidomics, to assess changes in endogenous proteolytic activity by analyzing the low molecular weight (LMW) component of blood. The integrated proteomic and peptidomic analysis of plasma samples identified a number of cytoskeletal and Ca2+-binding proteins and their proteolytic fragments in the disease samples. The measurements were compared to healthy donors and several of the observed differential quantitations were independently verified by ELISA. The identified changes in plasma proteome and peptidome, and the underlying changes in glycosylation together with altered endogenous protease activity may result in the generation of novel autoantigens. We and others have confirmed this hypothesis by the observation of autoantibodies in patients and upon extension of these studies to larger populations of patient; we may gain additional understanding of the role of etiological factors in different disease pathways.