Catalytic antibodies in clinical and experimental pathology: human and mouse models

Most of the data accumulated through studies on natural catalytic autoantibodies indicate that production scales up markedly in pathological abnormalities. We have previously described an increased level of DNA-hydrolyzing autoantibodies in the sera of patients with various autoimmune disorders [sys...

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Bibliographic Details
Published in:Journal of immunological methods 2002-11, Vol.269 (1), p.197-211
Main Authors: Ponomarenko, Natalya A, Durova, Oxana M, Vorobiev, Ivan I, Aleksandrova, Elena S, Telegin, Georgy B, Chamborant, Olga G, Sidorik, Lyudmila L, Suchkov, Sergei V, Alekberova, Zemfira S, Gnuchev, Nikolay V, Gabibov, Alexander G
Format: Article
Language:English
Subjects:
Animals
Antibodies, Catalytic - metabolism
Autoantibodies - metabolism
Autoimmune mice
Autoimmune myocarditis (AM)
Catalytic antibodies
Disease Models, Animal
DNA - metabolism
DNA-hydrolyzing abzymes (DNA-abzymes)
Endopeptidases - metabolism
Fluorescence assay technique (FAT)
Humans
Lupus Erythematosus, Systemic - immunology
Lupus Erythematosus, Systemic - pathology
Mice
Mice, Inbred MRL lpr
MRL-lpr/lpr
Multiple sclerosis (MS)
Multiple Sclerosis - immunology
Multiple Sclerosis - pathology
NZB×NZW
Proteolytic abzymes (protabzymes)
SJL/J
Systemic lupus erythematosus (SLE)
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Summary:Most of the data accumulated through studies on natural catalytic autoantibodies indicate that production scales up markedly in pathological abnormalities. We have previously described an increased level of DNA-hydrolyzing autoantibodies in the sera of patients with various autoimmune disorders [systemic lupus erythematosus (SLE), rheumatoid arthritis, scleroderma], HIV infection and lymphoproliferative diseases accompanied by autoimmune manifestations. In the present study, we show that an increased level of catalytic activity of autoantibodies can be observed in the sera of autoimmune mice, thus providing a fundamental insight into the medical relevance of abzymes. Polyclonal autoantibodies purified from sera of NZB/W, MRL-lpr/lpr and SJL/J mice show proteolytic and DNA-hydrolyzing activities, as opposed to those harvested from non-autoimmune BALB/c mice. The expressiveness of the catalytic activity was strongly dependent on the age of the animal. The highest levels of catalytic activity were found in the sera of mice aged between 8 and 12 months; the lowest level was typical of younger animals whose age ranged from 6 to 8 weeks. Specific inhibition assays of the catalytic activities were performed to throw light on the nature of the abzyme activity. Within a cohort of aging animals, a strong correlation between marked autoimmune abnormalities and levels of catalytic activities has been established. Nonimmunized SJL/J mice revealed specific immune responses to myelin basic protein (MBP), skeletal muscle myosin (skMyo) and cardiac myosin (Myo), and highly purified antibodies from their serum show specific proteolytic attack against the target antigens. This finding prompted us to undertake a more detailed study of specific antibody-mediated proteolysis in diseased humans. A targeted catalytic response was originally demonstrated against MBP and Myo in multiple sclerosis and myocarditis patients, respectively.
ISSN:0022-1759
1872-7905
DOI:10.1016/S0022-1759(02)00324-1