Several CCs became higher and reached values up to 0.1 to 0.55 and ?0.04 to ?0.47 after the division of cohort into subgroups of individuals with main progressing, secondary progressing and remitting course of the disease [14]. The groups of primary progressing remitting course and secondary progressing course of MS KMT6A patients were not homogenous with respect to the patients’ characteristics, and their further subdivision using cluster and factorial analysis revealed high statistically significant correlation coefficients [14]. content of lambda- and kappa-IgGs as well as IgGs of four different subclasses (IgG1-IgG4) in CSF and sera of MS individuals. The average relative content of lambda-IgGs and kappa CIgGs in the case of CSFs (8.0 and 92.0%) and sera (12.3 and 87.7%) are comparable, while IgG1, IgG2, IgG3, and IgG4: CSF – 40.4, 49.0, 8.2, and 2.5% of total IgGs, respectively and the sera – 53.6, 36.0, 5.6, and 4.8%, decreased in different order. Electrophoretically and immunologically homogeneous IgGs were acquired by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF efficiently hydrolyze MBP and that their average specific catalytic activity is definitely unpredictably 54-fold higher than that of Abdominal muscles from sera of the same MS individuals. Some possible reasons of these findings are discussed. We suggest that anti-MBP abzymes of CSF may promote important neuropathologic mechanisms with this chronic inflammatory disorder and in MS pathogenesis development. Intro Artificial abzymes (catalytic Abs against transition state analogues of chemical reactions) and natural abzymes are novel biological catalysts that have attracted a lot of interest in recent years (examined in [1]C[5]). Artificial abzymes are abzymes against analogs of transition claims of catalytic reactions [1]C[5] or antiidiotypic Abs induced by a primary antigen, which may show some of their features including the catalytic activity (for review also observe [6]C[11]). During the past two decades it has become obvious that auto-antibodies (auto-Abs) from sera of individuals with different autoimmune diseases can possess enzymatic activities and that their occurrence is definitely a distinctive feature of autoimmune diseases (examined in [11]C[14]). Different abzymes may play a significant role in forming specific pathogenic patterns and medical settings in different autoimmune conditions through their broadened auto-Ab properties. Individuals with autoimmune diseases create Abs to nucleoprotein complexes, DNA and enzymes that participate in nucleic acid rate of metabolism [11]C[14]. In autoimmune diseases, there can be a spontaneous induction of anti-idiotypic antibodies, which are Abs elicited by a main Ceftobiprole medocaril antigen, including some with catalytic activity, or perhaps a transition from polyreactive catalytic activity to an autoantigen-directed activity. Natural abzymes hydrolyzing DNA, RNA, polysaccharides, oligopeptides, and proteins are present in the serum of individuals with several autoimmune and viral diseases (examined in [11]C[14]). Healthy humans do not develop abzymes Ceftobiprole medocaril with detectable DNase and RNase activities, their levels becoming usually within the borderline of level of sensitivity of the detection methods [11]C[14]. Multiple sclerosis (MS) is a chronic demyelinating pathology of the central nervous system presenting a serious medical and interpersonal problem. Its etiology remains unclear, and the most valid theory of its pathogenesis assigns the main role in the destruction of the myelin-proteolipid shell of axons to swelling related to autoimmune reactions ([15], and refs therein). Although the T-cell immune system plays a leading part in MS pathogenesis, the normal functioning of the B-cell system is also important for the development of the disease. An enhanced synthesis of immunoglobulins (usually IgGs), their free light chains and of a polyspecific DNA binding Abs interacting with phospholipids can be observed in MS individuals [15]. It was demonstrated, that myelin fundamental protein-component 1 (MBP-C1) from MS cells undergoes autocatalytic cleavage at slightly alkaline pH [16]. Importantly, one of the major peptides released contained the immunodominant epitope. The cleavage reaction was not inhibited by protease inhibitors, except for phenylmethanesulfonyl fluoride, a serine protease inhibitor. It has recently been shown that myelin fundamental protein (MBP)-hydrolyzing activity is an intrinsic house of IgGs, IgMs, and IgAs from sera of MS individuals [14], [17]C[21]. In addition, it was demonstrated that MS IgGs comprising lambda (-IgGs) and kappa (-IgGs) light chains as well as IgGs Ceftobiprole medocaril of all four subclasses (IgG1-IgG4) efficiently hydrolyze MBP [20]. Acknowledgement and degradation of MBP peptides by serum auto-Abs were confirmed like a novel biomarker for MS [22]. The founded MS drug Copaxone appears to.
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