Autoimmune processes and production of catalytically active antibodies-abzymes in prone to amyotrophic lateral sclerosis FUS(1-359) mice.

OBJECTIVE: It was shown previously that the development of not only many autoimmune (AIDs) but also neurological and neurodegenerative diseases (NDDs) including multiple sclerosis, tick-borne encephalitis, and schizophrenia in humans and experimental mice models occurs due to a specific destruction of the immune system. This error in the immune system leads to the formation of B lymphocytes producing adverse antibodies-abzymes possessing different catalytic activities. METHODS: One of the earliest and statistically reliable index of developments of autoimmune reactions is the appearance in the blood abzymes that are absent in conditionally healthy donors. We investigated the in time changes catalytic activities of Abs-abzymes using standard methods of enzymology. RESULTS: It was shown for the first time that, as in the case of various AIDs and NDDs, the early stages of ALS development in FUS(1-359) mice are also associated with the production of catalytic antibodies. CD-1 mice utilized for obtaining FUS(1-359) mice were also used. IgG samples were isolated from the blood of transgenic FUS(1-359) mice and their non-transgenic siblings (CD1) at different times. The first signs of ALS-like symptoms develop at the age of ≥ 2 months of life in FUS(1-359) mice, which was taken as zero time point, and then by ≥ 80 days of age, deep pathology was observed. It was shown for the first time that antibodies from the blood of FUS(1-359) mice exhibit DNase, amylase, phosphatase, and catalase catalytic activities beginning from 2 months of age. However, unlike non-transgenic siblings, the relative activity of mice IgGs was higher in FUS(1-359) mice. All activities of FUS(1-359) mice IgGs began to increase significantly starting from 20 to 30 days after beginning of experiments and achieved maximum upon reaching deep pathology. CONCLUSIONS: The data obtained indicate that in the early stages of ALS development in FUS(1-359) mice containing genes associated with this pathology in humans, there is a disruption of the immune system and production of abzymes that destroy components of blood, cells and tissues. One cannot exclude that such autoimmune reactions are important for development of ALS in FUS(1-359) mice.