Comparison of antibodies hydrolyzing myelin basic protein from the cerebrospinal fluid and serum of patients with multiple sclerosis

Visilii B Doronin; Taisiya A Parkhomenko; Massimiliano Castellazzi; Marina Padroni; Michela Pastore; Valentina N Buneva; Enrico Granieri; Georgy A Nevinsky

doi:10.1371/journal.pone.0107807

Comparison of antibodies hydrolyzing myelin basic protein from the cerebrospinal fluid and serum of patients with multiple sclerosis

PLoS One. 2014 Sep 29;9(9):e107807. doi: 10.1371/journal.pone.0107807. eCollection 2014.

Authors

Visilii B Doronin¹, Taisiya A Parkhomenko², Massimiliano Castellazzi³, Marina Padroni³, Michela Pastore³, Valentina N Buneva⁴, Enrico Granieri³, Georgy A Nevinsky⁴

Affiliations

¹ Novosibirsk Medical University, Ministry of Public Health of Russian Federation, Novosibirsk, Russia.
² Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Division, Novosibirsk, Russia.
³ Multiple Sclerosis Center, Department of Neurology, Ferrara University, Ferrara, Italy.
⁴ Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Division, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia.

Abstract

It was found that antibodies (Abs) against myelin basic protein (MBP) are the major components of the antibody response in multiple sclerosis (MS) patients. We have recently shown that IgGs from sera of MS patients are active in the hydrolysis of MBP. However, in literature there are no available data concerning possible MBP-hydrolyzing Abs in cerebrospinal fluid (CSF) of MS patients. We have shown that the average content of IgGs in their sera is about 195-fold higher than that in their CSF. Here we have compared, for the first time, the average content of lambda- and kappa-IgGs as well as IgGs of four different subclasses (IgG1-IgG4) in CSF and sera of MS patients. The average relative content of lambda-IgGs and kappa -IgGs 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 obtained 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 unpredictably ∼54-fold higher than that of Abs from sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that anti-MBP abzymes of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Autoantibodies / immunology*
Female
Humans
Hydrolysis
Male
Middle Aged
Multiple Sclerosis / blood
Multiple Sclerosis / cerebrospinal fluid
Multiple Sclerosis / immunology*
Myelin Basic Protein / blood
Myelin Basic Protein / cerebrospinal fluid
Myelin Basic Protein / immunology*
Young Adult

Substances

Autoantibodies
Myelin Basic Protein

Grants and funding

This study was in part supported in part by grants from the Presidium of the Russian Academy of Sciences (Molecular and Cellular Biology Program, 6.2; Russian Foundation for Basic Research (13-04-00208 and 13-04-00205), funds from the Siberian Division of the Russian Academy of Sciences and funds from the Regione Emilia Romagna, Italy (Ricerca Sanitaria Finalizzata). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.