Changes in different parameters, lymphocyte proliferation and hematopoietic progenitor colony formation in EAE mice treated with myelin oligodendrocyte glycoprotein.

Vasilii B Doronin,Irina A Orlovskaya,Georgy A Nevinsky,Nelly A Popova,Thomas Budde,Valentina N Buneva,Ludmila B Toporkova,Alexey Korablev,Alina A Alshevskaja,Sergei V Sennikov,Sven G Meuth,Taisiya A Parkhomenko,Julia A Lopatnikova

doi:10.1111/jcmm.12704

Abstract

Myelin oligodendrocyte glycoprotein (MOG) is an antigen of the myelin sheath, which may trigger immune cell responses and the production of auto-antibodies in multiple sclerosis (MS). In this study, we used MOG(35-55) -induced experimental autoimmune encephalomyelitis (EAE), a model of human MS, to assess the production of catalytically active immunoglobulin G (IgG) antibodies or abzymes which have been shown to be present in sera of patients with several autoimmune diseases. Here, we show that IgGs from the sera of control C57BL/6 mice are catalytically inactive. During development of EAE, a specific reorganization of the immune system of mice occurred leading to a condition which was associated with the generation of catalytically active IgGs hydrolysing DNA, myelin basic protein (MBP) and MOG which was associated with increased proteinuria, changes in differentiation of mice bone marrow hematopoietic stem cells (HSCs) and an increase in proliferation of lymphocytes in bone marrow, spleen and thymus as well as a significant suppression of cell apoptosis in these organs. The strongest alterations were found in the early disease phase (18-24 days after immunization) and were less pronounced in later EAE stages (40 days after EAE induction). We conclude that a significant increase in DNase and proteolytic activities of antibodies may be considered the earliest statistically significant marker of MOG-induced EAE in mice. The possible differences in immune system reorganizations during preclinical phases of the disease, acute and late EAE, leading to production of different auto-antibodies and abzymes as well other changes are discussed.

Highlights

Multiple sclerosis is a chronic demyelinating disease of the central nervous system
It has recently been shown that the specific reorganization of the immune system during the spontaneous development of a profound systemic lupus erythematosus (SLE)-like pathology in MRL-lpr/lpr mice is associated with changes in the differentiation profile of bone marrow hematopoietic stem cells (HSCs) and the level of lymphocyte proliferation in combination with the production of DNase, ATPase and amylase abzymes [34,35,36]
The homogeneity of typical 150-kD untr-IgGmix and tr-IgGmix was confirmed by SDS-PAGE with silver staining, which showed a single band under non-reducing conditions (Fig. 2A) and two bands corresponding to the H and L chains after antibody reduction (Fig. 2B)

Summary

Introduction

Multiple sclerosis is a chronic demyelinating disease of the central nervous system. Its aetiology remains unclear, and the most widely accepted theory of MS pathogenesis assigns a main role to the destruction of myelin by the inflammation related to autoimmune. It has recently been shown that the specific reorganization of the immune system during the spontaneous development of a profound SLE-like pathology in MRL-lpr/lpr mice is associated with changes in the differentiation profile of bone marrow HSCs and the level of lymphocyte proliferation in combination with the production of DNase, ATPase and amylase abzymes [34,35,36]. Immunization of healthy mice with DNA leads to the production of Abs with DNase activity; it is only associated with increased lymphocyte proliferation and suppression of lymphocyte apoptosis in different organs (especially the spleen), but not with a change in the differentiation of bone marrow cells [34,35,36]. For the first time, the correlation of the relative activities of mouse IgGs in the hydrolysis of MBP, MOG and DNA with some biochemical markers of EAE pathology (proteinuria, Abs titres to MBP, MOG and DNA) as well as with changes in the differentiation profile and the level of proliferation of bone marrow HSCs, proliferation and apoptosis of lymphocytes in different organs during various time-points before and after mice treatment with MOG

Materials and methods

Discussion

Findings

Conflicts of interest