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

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.

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

“…In addition, the level of lymphocyte proliferation as well as cell apoptosis in different organs including bone marrow of healthy MRL-lpr/lpr and EAE mice, at stages of their prediseases and deep pathologies were also comparable [32]. In addition, it was shown that abzymes hydrolyzing MBP are formed in the early stages of human MS, unlike in later stages of SLE, while the reverse situation was observed for abzymes with DNase activity [70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87].…”

“…For example, using experimental C57BL/6 autoimmune encephalomyelitis (EAE) mice (a model mimicking human MS), it was recently shown that spontaneous EAE development leads to the production of Abs to myelin basic protein (MBP) and DNA and to Abzs efficiently hydrolyzing these substrates, which associated with significant changes of the differentiation profile and level of lymphocytes proliferation of mice bone marrow HSC [32]. Immunization of these mice with MOG35 results in a very strong acceleration in the development of EAE and a very strong increase of the relative activities of abzymes hydrolyzing MOG, MBP, and DNA.…”

“…Interplay between these processes is determined by genetic factors, and may be modulated by hormones, complicated by a many of secondary factors, may explain the wide Figure 5. The relative content (%) of total erythroid cells (BFU-E+ CFU-E), CFU-GM, and CFU-GEMM colonies in the case of healthy CBA, conditionally healthy MRL-lpr/lpr and C57BL/6 mice at 3 months of age, and after development of, respectively, EAE and SLE is shown [32]. For C57BL/6 mice, the relative contents of progenitor colonies after spontaneous and MOG-stimulated development of EAE are given.…”

“…However, specific positive roles have been also proposed for several abzymes. Increase in Abzs activities is associated with a specific reorganization of the immune system including change in differentiation profile and level of proliferation of hematopoietic stem cells of bone marrow as well as lymphocyte proliferation in different organs of SLE and experimental autoimmune encephalomyelitis (EAE) in mice [29][30][31][32]. Different mechanisms of abzymes production were revealed in healthy animals after external immunization and in autoimmune mice during their spontaneous or antigen-induced development of autoimmune processes [29][30][31][32].…”

Changes in cell differentiation and proliferation lead to production of abzymes in EAE mice treated with DNA–Histone complexes

“…At that time, antibody titres for various anti‐antigens correspond to a range of indices typical for healthy humans and mice. A detectable level of abzymes can indicate the disease onset or pre‐disease stage, while an increase in catalytic activities follows the development of clear pathological symptoms . To understand the disease, it is therefore essential to identify all possible parallel and complementary mechanisms of MS development.…”