**1. Introduction**

Classically, antibodies (Abs) have been characterized as proteins produced by the immune system, which have the sole function of binding other molecules, called antigens, and eliciting an immune response. In this classical conception, Abs act similarly to enzymes in specific binding to other molecules. However, in contrast to enzymes, they do not have the ability to catalyze chemical conversions of their bound partners. For the vast majority of Abs, this observation is correct. However, it was shown that antibodies against chemically stable analogues of the transition states of chemical reaction can possess different enzymatic activities [1–8]. These artificial catalytic Abs were termed "abzymes" (derived from antibody enzymes). Abzymes (Abzs) catalyzing more than 100 distinct chemical reactions are novel biological catalysts that attracted interest in recent years reviewed repeatedly [1–8].

The first example of natural Abzs was an IgG found in bronchial asthma patients, which hydrolyzed intestinal vasoactive peptide [9], the second Abz was an IgG with DNase activity in a systemic lupus erythematosus (SLE) patient [10], and the third was an IgG with RNase activity in an SLE patient [11]. Later, catalytic IgGs and/or IgAs, IgMs hydrolyzing different oligopeptides, proteins, DNA, RNA, nucleotides, and polysaccharides were detected in the sera of patients with several autoimmune diseases (ADs) and some viral pathologies (for review see [8, 12–21] and refs therein).

Some Abs and auto-Abs with different catalytic activities may be induced spontaneously by primary antigens and can have characteristics of the primary antigen, including the catalytic activity of idiotypic and/or anti-idiotypic Abs [8, 12–21]. Healthy humans usually do not develop catalytic Abs or their activities are very low. Detection of Abzs was shown to be the earliest indicator of development of different ADs [8, 12–21]. At the early stages of ADs, the repertoire of Abzs is usually relatively narrow, but it greatly expands with the progress of the disease, leading to the generation of catalytically diverse Abs with various activities and functions [8, 12–21]. Some Abzs are cytotoxic and can play an important negative role in the pathogenesis of different ADs, while positive roles have been also proposed for other Abzs [8, 12–21]. Abzs activities increase in association with a specific reorganization of the immune system, such as differentiation and proliferation of bone marrow hematopoietic stem cells and lymphocyte proliferation in various organs of SLE mice [22–24]. Different mechanisms of Abzs production exist in healthy externally immunized animals and of autoimmune mammals during the development of pathological reactions were revealed ([8, 12–24], see below).

Catalysis by auto-Abzs is potentially applicable in many different fields, including efficient catalysts, the generation of new drugs, and evaluation of the functional roles of Abzs in innate and adaptive immunity, the understanding of self-tolerance and of destructive responses in ADs [25–27]. Abzs can be employed for the development of new of drugs, some of which may be useful for therapy.

during preclinical phases of the disease, acute and late EAE, leading to production of

**Keywords:** catalytic antibodies, autoimmunity, hematopoietic stem cells, multiple

Classically, antibodies (Abs) have been characterized as proteins produced by the immune system, which have the sole function of binding other molecules, called antigens, and eliciting an immune response. In this classical conception, Abs act similarly to enzymes in specific binding to other molecules. However, in contrast to enzymes, they do not have the ability to catalyze chemical conversions of their bound partners. For the vast majority of Abs, this observation is correct. However, it was shown that antibodies against chemically stable analogues of the transition states of chemical reaction can possess different enzymatic activities [1–8]. These artificial catalytic Abs were termed "abzymes" (derived from antibody enzymes). Abzymes (Abzs) catalyzing more than 100 distinct chemical reactions are novel biological catalysts that

The first example of natural Abzs was an IgG found in bronchial asthma patients, which hydrolyzed intestinal vasoactive peptide [9], the second Abz was an IgG with DNase activity in a systemic lupus erythematosus (SLE) patient [10], and the third was an IgG with RNase activity in an SLE patient [11]. Later, catalytic IgGs and/or IgAs, IgMs hydrolyzing different oligopeptides, proteins, DNA, RNA, nucleotides, and polysaccharides were detected in the sera of patients with several autoimmune diseases (ADs) and some viral pathologies (for

Some Abs and auto-Abs with different catalytic activities may be induced spontaneously by primary antigens and can have characteristics of the primary antigen, including the catalytic activity of idiotypic and/or anti-idiotypic Abs [8, 12–21]. Healthy humans usually do not develop catalytic Abs or their activities are very low. Detection of Abzs was shown to be the earliest indicator of development of different ADs [8, 12–21]. At the early stages of ADs, the repertoire of Abzs is usually relatively narrow, but it greatly expands with the progress of the disease, leading to the generation of catalytically diverse Abs with various activities and functions [8, 12–21]. Some Abzs are cytotoxic and can play an important negative role in the pathogenesis of different ADs, while positive roles have been also proposed for other Abzs [8, 12–21]. Abzs activities increase in association with a specific reorganization of the immune system, such as differentiation and proliferation of bone marrow hematopoietic stem cells and lymphocyte proliferation in various organs of SLE mice [22–24]. Different mechanisms of Abzs production exist in healthy externally immunized animals and of autoimmune mammals during the development of pathological reactions were revealed ([8, 12–24], see below).

Catalysis by auto-Abzs is potentially applicable in many different fields, including efficient catalysts, the generation of new drugs, and evaluation of the functional roles of Abzs in innate

different autoantibodies and Abzs as well other changes are discussed.

sclerosis, cell differentiation, cell proliferation

attracted interest in recent years reviewed repeatedly [1–8].

review see [8, 12–21] and refs therein).

**1. Introduction**

100 Trending Topics in Multiple Sclerosis

In this review, Abzs with different catalytic activities in multiple sclerosis (MS) are compared with other Abzs in ADs. In addition, a role of defects of immune systems leading to 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 associated with the production of Abzs is discussed.
