TY - JOUR

T1 - Autoimmunity and immune system dysregulation in schizophrenia

T2 - IgGs from sera of patients hydrolyze myelin basic protein

AU - Parshukova, Daria

AU - Smirnova, Liudmila P.

AU - Ermakov, Evgeny A.

AU - Bokhan, Nikolay A.

AU - Semke, Arkadiy V.

AU - Ivanova, Svetlana A.

AU - Buneva, Valentina N.

AU - Nevinsky, Georgy A.

N1 - Publisher Copyright: © 2018 John Wiley & Sons, Ltd.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

KW - catalytic IgG

KW - human blood

KW - hydrolysis of myelin basic protein

KW - multiple sclerosis

KW - schizophrenia

KW - systemic lupus erythematosus

KW - AUTOANTIBODIES

KW - COLONY FORMATION

KW - DISORDERS

KW - PREVALENCE

KW - METAL-DEPENDENT HYDROLYSIS

KW - MULTIPLE-SCLEROSIS

KW - CATALYTIC HETEROGENEITY

KW - DIVERSITY

KW - SIGA ANTIBODIES

KW - LIGHT-CHAINS

UR - http://www.scopus.com/inward/record.url?scp=85052404289&partnerID=8YFLogxK

U2 - 10.1002/jmr.2759

DO - 10.1002/jmr.2759

M3 - Article

C2 - 30112774

AN - SCOPUS:85052404289

VL - 32

JO - Journal of Molecular Recognition

JF - Journal of Molecular Recognition

SN - 0952-3499

IS - 2

M1 - e2759

ER -