Autoimmunity and immune system dysregulation in schizophrenia: IgGs from sera of patients hydrolyze myelin basic protein

Abstract

Several different theories of schizophrenia (SCZ) were discussed; the causes of this disease are not yet clear. Using ELISA, it was shown that titers of autoantibodies against myelin basic protein (MBP) in SCZ patients are ~1.8-fold higher than in healthy individuals but 5.0-fold lower than in patients with multiple sclerosis. Several rigid criteria were checked to show that the MBP-hydrolyzing activity is an intrinsic property of SCZ IgGs. Approximately 82% electrophoretically homogeneous SCZ IgGs purified using several affinity sorbents including Sepharose with immobilized MBP hydrolyze specifically only MBP but not many other tested proteins. The average relative activity of IgGs from patients with negative symptoms was 2.5-fold higher than that of patients with positive symptoms of SCZ, and it increases with the duration of this pathology. It was shown that abzymes are the earliest statistically significant markers of many autoimmune pathologies. Our findings surmise that the immune systems of individual SCZ patients can generate a variety of anti-MBP abzymes with different catalytic properties, which can attack MBP of the myelin-proteolipid shell of axons. Therefore, autoimmune processes together with other mechanisms can play an important role in SCZ pathogenesis. MBP-hydrolyzing antibodies were previously detected in the blood of 80% to 90% of patients with systemic lupus erythematosus (SLE) and multiple sclerosis (MS). In addition, some similar neuropsychiatric indicators of disease common to SLE, MS, and SCZ were described in the literature. Thus, the destruction of the myelin sheath and the production of MBP-hydrolyzing antibodies can be a common phenomenon for some different diseases.

Natural Catalytic IgGs Hydrolyzing Histones in Schizophrenia: Are They the Link between Humoral Immunity and Inflammation?

“…Therefore, catalytic cross-reactive antibodies against histones and MBP can play a negative role, contributing to the development of the disease [ 47 ]. Recently, we detected catalytic antibodies in serum of patients with schizophrenia that hydrolyze MBP [ 48 ]. Therefore, it was interesting to establish whether histone-hydrolyzing antibodies are formed in schizophrenia.…”

Production of Abzymes in Th, CBA, and C57BL/6 Mice before and after MOG Treatment: Comparing Changes in Cell Differentiation and Proliferation

“…In addition, DNA-and MBP-hydrolyzing abzymes were found in SLE and MS patients [24,25]. Moreover, abzymes hydrolyzing DNA and MBP was revealed in sera of patients with schizophrenia also demonstrating neuropsychiatric components [44,45]. Thus, changes in the HSCs differentiation profiles and the intensity of production of abzymes with various activities in patients with different AIDs and experimental animals prone to the development of autoimmune reactions may vary in one way or another.…”

IgG-Dependent Dismutation of Superoxide in Patients with Different Types of Multiple Sclerosis and Healthy Subjects

“…The K m and V max values were estimated using the nonlinear regression method in the Origin Pro v.8.6 program and were presented as linear transformations using a Lineweaver-Burk plot [54]. The value of K cat was determined by the formula K cat = V max /½AB, where [AB] is the total concentration of IgGs in the reaction mixture [40,42,49]. Errors in the values were within 7-15%.…”

“…The stability of any abzymes to these conditions is relatively low, so their activity is significantly reduced immediately after gel filtration. It has been previously shown that activity of IgGs was restored after their neutral solutions were kept at 40°C for 1-2 weeks [40,42].…”