Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is known as a systemic polyethiologic diffuse autoimmune disease characterized by connective tissue disorganization and the paramount damage of skin and visceral capillaries. Usually, SLE symptoms include high fever, hair loss, mouth ulcers, chest pain, swollen lymph nodes, painful and swollen joints, increased fatigue, and appearance of red rash more often on the face. The exact reason of SLE appearance is not really clear. Detection of catalytic Abs (abzymes) was shown to be the earliest indicator of different AI disease development. Some abzymes are cytotoxic and can play a dangerous negative role in the pathogenesis of AI diseases. SLE is characterized by the appearance of abzymes with several different catalytic functions including hydrolysis of peptides and proteins, DNA, RNA, and oligosaccharides. In addition, monoclonal SLE abzymes are characterized by extraordinary diversity in the affinity to the substrates, physicochemical and catalytic characteristics, optimal conditions of catalysis, cytotoxicity, etc. Production of abzymes in SLE mice is associated with changes in the differentiation of hematopoietic stem cells of bone marrow, increase in lymphocyte proliferation, and significant suppression of cell apoptosis in different organs. In this chapter, abzymes with different catalytic activities in SLE are described.

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

“…Current data demonstrate the appearance of myelin basic protein (MBP)‐ and DNA‐hydrolysing abzymes in the blood of patients with MS, SLE and several other AIDs . IgGs from the CSF of MS patients, which hydrolyse MBP, DNA and polysaccharides, are on average 30‐ to 60‐fold higher than those taken from the sera of the same patients .…”

“…It has been shown that multifunctional cytokines can influence the human immune system leading to its dysregulation and resulting in the development of different AIDs . In addition, an important and harmful role in the development of MS and other AIDs can be attributed to auto‐Abs with catalytic activities (abzymes; ABZs) …”

“…Researchers conducted during the last 30 years have revealed different enzymatic activities for auto‐Abs. Auto‐Ab elaboration is a specific feature of AID patients . Similar to artificial abzymes, natural ABZs are antibodies against enzyme substrates acting as protein haptens and mimicking transition states of chemical reactions.…”

“…Similar to artificial abzymes, natural ABZs are antibodies against enzyme substrates acting as protein haptens and mimicking transition states of chemical reactions. Anti‐idiotypic ABZs against catalytic enzyme centres also possess catalytic activities . Abzymes with many different enzymatic activities were revealed as the earliest and most significant markers of onset and development of various AIDs in humans and mammals including systemic lupus erythematosus (SLE), MS and EAE in experimental mice.…”

“…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.…”