**Acknowledgements**

This research was made possible by grants mainly from Russian Science Foundation (No. 16-15-10103 to G. A. Nevinsky), purification of IgGs was made grants from the Presidium of the Russian Academy of Sciences (Molecular and Cellular Biology Program, 6.7) and from Russian Foundation for Basic Research (No. 16-04-00603, and 14-04-31281)

#### **Abbreviations**

MS patients demonstrate some similarity with SLE patients in the development of the same medical, biochemical, immunological indexes including specific plaques in the brain, which appear on late stages of these diseases. Anti-DNA Abs is known as the main important diagnostic index for SLE, but these Abs were also identified as a major component of the

It is known that demyelinating plaques appear at relatively late stages in the development of MS, and their presence detected by brain MRI are essential for the diagnosis according to Mc Donald's criteria. At the same time, the detection of Abzs with DNase- and MBP-hydrolyzing activities was shown to be the earliest indicator of development of MS. Catalytic activities of nuclease and protease Abzs are usually very easily detectable at the onset of MS and other autoimmune diseases when the total concentrations of Abs to DNA, MBP, or other autoantigens are still low and correspond to their ranges in healthy donors. Although Abzs with low activity can sometimes be detected in conventionally healthy people, the RAs of Abzs from MS and SLE patients are usually 1–3 orders of magnitude higher. Therefore, an appearance of some Abzs or a 10- to 100-fold increase in the activity of others over the average Abzs indices for healthy donors may be used as the earliest markers of autoimmune reactions in patients

Recognition and degradation of MBP peptides by serum auto-Abs was stated as a novel biomarker for MS [82]. But IgGs from SLE patients also efficiently hydrolyze MBP and oligopeptides corresponding to different AGDs of MBP [84, 85]. Thus, it is clear that early diagnostics of MS requires the use of all known independent methods to exclude SLE and probably other possible diseases leading to a formation of DNA- and MBP-hydrolyzing Abzs. Nevertheless, even revealing of DNase and RNase Abzs on early stages of MS may be very useful. For example, in the case of three patients, we have suggested the possibility of initial stages of MS, but the symptoms did not meet all Poser's and Mc Donald´s criteria. However, Abs found in the sera of these patients demonstrated a high DNase activity speaking in favor of a possibility of an early stage of MS. One and a half years later, these patients met Poser's and Mc Donald´ criteria, and after 2–3 consecutive years, brain plaques were also found in

The immune systems of individual MS patients generate Abzs, which can attack MBP of myelin-proteolipid shell of axons, while an established MS therapeutic Copaxone inhibits specific MBP-hydrolyzing activity of Abzs [82]. It means that the development of MS and probably SLE or other diseases associated with demyelination can be suppressed by specific

All data indicative of the fact that CFU-E cells can be precursors of cells producing Abzs in different organs. In this connection, it should be mentioned that IgGs from CSF of patients with MS 30- to 50-fold more active in the hydrolysis of MBP, DNA, and oligosaccharides, then Abs from sera of the same patients [110, 111]. It means that even CSFs of patients with MS contain specific cells producing these catalytically active Abs. Moreover, DNase Abzs form SLE and MS patients are cytotoxic and induce apoptotic cell death. SLE and MS Abzs efficiently hydrolyzed polysaccharides. Therefore, it is very possible that abzymes with DNase, amylase,

intrathecal IgGs in brain and CNS cells of MS patients [40].

with MS and other autoimmune diseases.

136 Trending Topics in Multiple Sclerosis

inhibitors of MBP-hydrolyzing IgGs, IgAs, and IgMs.

these patients.

Abs, antibodies; Abzs, abzymes, or catalytically active antibodies; AGDs, antigenic determi‐ nants; AI, autoimmune; AD, autoimmune disease; AIDS, human immunodeficiency syn‐ drome; a/u, arbitrary units; BSA, bovine serum albumin; CC, correlation coefficient; HSCs, hematopoietic stem cells; CBA, (CBAxC57BL)F1 mice; MBP, human myelin basic protein; OP-17, OP-19, OP-21, and OP-25―17-25mer oligopeptides corresponding to four known MBP cleavage sites; MS, multiple sclerosis; m-BSA, methylated BSA; nat-DNA and den-DNA, native and denatured DNA, respectively; ODN, oligonucleotide, OP, oligopeptide; SLE- systemic lupus erythematosus, SDS-PAGE, SDS-polyacrylamide gel electrophoresis; RA, relative activity.
