Hydrolysis of myelin basic protein by IgM and IgA antibodies from the sera of patients with multiple sclerosis.
Valentina Buneva, Boris Doronin, Olga Tyshkevich, Alexey Boiko, Evgenii Gusev, Olga Favorova, Gregory Nevinsky
Med Sci Monit 2005; 11(8): BR266-272
Available online: 2005-08-01
Background: The presence of abzymes (Abzs) in human sera is a specificfeature of different autoimmune pathologies. We have shown that IgGs of patients with multiple sclerosis(MS) specifically hydrolyze human myelin basic protein (hMBP). However, the presence of hMBP-hydrolyzingMS IgMs and IgAs in patients with MS has not been studied. Material/Methods: Homogeneous IgM and IgAfractions were isolated from human sera by affinity chromatography on different adsorbents. The Ab-dependenthydrolysis of hMBP was analyzed using SDS-PAGE. Results: We present evidence showing that MS IgMs andIgAs (but not Abs from the sera of healthy individuals) catalyze the hydrolysis of hMBP. Specific enzymaticactivities of IgMs and sIgAs from sera of any single patient were usually significantly higher than thoseof IgGs. Specific inhibitors of acidic and thiol proteases demonstrated a weak effect on proteolyticactivity of IgGs and IgMs. However, specific inhibitors of serine proteases (AEBSF, PMSF, and benzamidine)significantly inhibited proteolytic activity. IgMs and IgAs hydrolyze specifically both human and pigMBP but not many other tested proteins. Although the biological function of this proteolytic activityis not known, it is clear that MBP-hydrolyzing Abs may play an important role in MS pathogenesis. Conclusions:The findings display the generation by the immune systems of individual MS patients of a variety of polyclonalIgGs, IgMs, and IgAs with different proteolytic properties, which hydrolyze MBP, the major protein componentof the myelin-proteolipid shell of axons and a well-known MS autoantigen.
Keywords: Adolescent, Adult, Animals, Chromatography, Gel, Hydrolysis, Immunoglobulin G - blood, Immunoglobulin G - immunology, Immunoglobulin M - blood, Immunoglobulin M - immunology, Multiple Sclerosis - immunology, Multiple Sclerosis - metabolism, Myelin Basic Proteins - metabolism, Swine, Adolescent, Adult, Animals, Chromatography, Gel, Hydrolysis, Immunoglobulin G - immunology, Immunoglobulin M - immunology, Multiple Sclerosis - metabolism, Myelin Basic Protein - metabolism, Swine