IgGs containing λ‐ and κ‐type light chains and of all subclasses (IgG1–IgG4) from the sera of patients with autoimmune diseases and viral and bacterial infections hydrolyze DNA

Abstract

We present the first evidence demonstrating that small fractions of IgGs of all four subclasses (IgG1-IgG4) from patients with viral (tick-borne encephalitis), bacterial infections (streptococcal infection or erysipelas), and suppurative surgical infections caused by epidermal staphylococci as well as from patients with autoimmune diseases (systemic lupus erythematosus and multiple sclerosis) are catalytically active in the hydrolysis of supercoiled DNA. The hydrolysis of DNA was analyzed by agarose gel electrophoresis. The catalytic activities of nonfractionated IgGs increased in the following order: tick-borne encephalitis < suppurative surgical infection < streptococcal infection < multiple sclerosis < systemic lupus erythematosus, whereas IgGs of healthy donors were inactive. However, the pools of antibodies corresponding to any particular disease were characterized by a specific ratio of IgGs of all four subclasses (IgG1-IgG4) and IgGs containing λ- and κ-type light chains, and each of these subfractions of immunoglobulins demonstrated characteristic relative DNase activity. The relative activities of IgGs containing λ-type light chains may on average be higher, lower, or comparable with those for IgGs with κ-type light chains. The relative contributions of IgGs of different subclasses to the total activity of IgGs also varied widely in the case of various diseases: IgG1 (7%-45%), IgG2 (0.4%-73%), IgG3 (0%-12%), and IgG4 (9%-66%). Thus, immune systems of patients with different diseases can generate a variety of anti-DNA abzymes of different types and with different catalytic properties, which can play an important role in the pathogenesis or protection from the development of these diseases.

Natural IgG against S-Protein and RBD of SARS-CoV-2 Do Not Bind and Hydrolyze DNA and Are Not Autoimmune

“…In addition, viruses can cause abnormalities in the human immune system, resulting in the production of antibodies with catalytic activity (abzymes) [18,19]. Catalytic antibodies have been found in several viral infections (tick-borne encephalitis, HIV infection [20,21]), bacterial infections [22], and several autoimmune diseases [23,24]. Autoimmune diseases are accompanied by the formation of catalytic antibodies hydrolyzing DNA, RNA, oligonucleotides, proteins, peptides, and oligosaccharides and possessing oxidoreductase activity [18,21,[25][26][27][28], and other activities [29,30].…”

Desialylation of dying cells with catalytically active antibodies possessing sialidase activity facilitate their clearance by human macrophages

“…While multiple myeloma is characterized by overgrowth of hyperactive antibody-producing cells, the reason for the appearance of these abzymes in the blood of patients with SLE remains a mystery. Interestingly, DNA-hydrolyzing abzymes have also been reported to be most prevalent in patients with SLE [16]. A possible explanation for the appearance of abzymes with sialidase activity in the sera of patients with SLE is that increased sialidase activity on the surface of apoptotic cells [1,17] and its prolonged exposure to the immune system during impaired cell clearance results in the formation of anti-idiotypic antibodies against the active centre of a sialidase which, in turn, allows stabilization of the transitional intermediate of the catalyzed sialidase reaction and reduction of the energy barrier needed to perform sialic acid cleavage [18,19].…”