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Catalytic Antibodies in Bipolar Disorder: Serum IgGs Hydrolyze Myelin Basic Protein
Authors:Daria A Kamaeva  Liudmila P Smirnova  Svetlana N Vasilieva  Daria V Kazantseva  Alisa R Vasilieva  Svetlana A Ivanova
Affiliation:1.Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia; (L.P.S.); (S.N.V.); (S.A.I.);2.Department of Biomedicine, Siberian State Medical University, 634055 Tomsk, Russia; (D.V.K.); (A.R.V.)
Abstract:The pathogenesis of bipolar affective disorder is associated with immunological imbalances, a general pro-inflammatory status, neuroinflammation, and impaired white matter integrity. Myelin basic protein (MBP) is one of the major proteins in the myelin sheath of brain oligodendrocytes. For the first time, we have shown that IgGs isolated from sera of bipolar patients can effectively hydrolyze human myelin basic protein (MBP), unlike other test proteins. Several stringent criteria were applied to assign the studied activity to serum IgG. The level of MBP-hydrolyzing activity of IgG from patients with bipolar disorder was statistically significantly 1.6-folds higher than that of healthy individuals. This article presents a detailed characterization of the catalytic properties of MBP-hydrolyzing antibodies in bipolar disorder, including the substrate specificity, inhibitory analysis, pH dependence of hydrolysis, and kinetic parameters of IgG-dependent MBP hydrolysis, providing the heterogeneity of polyclonal MBP-hydrolyzing IgGs and their difference from canonical proteases. The ability of serum IgG to hydrolyze MBP in bipolar disorder may become an additional link between the processes of myelin damage and inflammation.
Keywords:bipolar disorder  catalytic IgG  abzymes  myelin  myelin basic protein  antibodies  humoral immunity
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