Hydrolysis of myelin basic protein by polyclonal catalytic IgGs from the sera of patients with multiple sclerosis.
Various catalytic antibodies or abzymes have been detected recently in the sera of patients with several autoimmune pathologies, where their presence is most probably associated with autoimmunization. Recently we have shown that DNase, RNase, and polysaccharide-hydrolyzing activities are associated with IgGs from the sera of patients with multiple sclerosis (MS). Here we present evidence demonstrating that highly purified MS IgGs (but not Igs from the sera of healthy individuals) catalyze specifically hydrolysis of human myelin basic protein (hMBP). In contrast to many known proteases, IgGs do not hydrolyze many other different proteins. Specific inhibitors of acidic and thiol proteases have no remarkable effect on proteolytic activity of IgGs. However, specific inhibitor of serine (PMSF, AEBSF, and benzamidin) and metal-dependent (EDTA) proteases significantly inhibit activity of proteolytic abzymes. Interestingly, the ratio of serine-like and metal-dependent activities of MS IgGs varied very much from patient to patient. The findings speak in favor of the generation by the immune systems of individual MS patients of a variety of polyclonal anti-MBP IgGs with different catalytic properties.
Polosukhina
Darya I
DI
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Novosibirsk 630090, Russia.
Kanyshkova
Tatyana G
TG
Doronin
Boris M
BM
Tyshkevich
Olga B
OB
Buneva
Valentina N
VN
Boiko
Alexey N
AN
Gusev
Evgenii I
EI
Favorova
Olga O
OO
Nevinsky
Georgy A
GA
D000293:Adolescent; D000328:Adult; D017151:Antibodies, Catalytic / Q000097:blood / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D004676:Myelin Basic Protein / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology
D017151:Antibodies, Catalytic; D001323:Autoantibodies; D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D011480:Protease Inhibitors