Affinity and catalytic heterogeneity of polyclonal myelin basic protein-hydrolyzing IgGs from sera of patients with multiple sclerosis.
Human myelin basic protein (hMBP)-hydrolyzing activity was recently shown to be an intrinsic property of antibodies (Abs) from multiple sclerosis (MS) patients. Here, we present the first evidence demonstrating a significant diversity of different fractions of polyclonal IgGs (pIgGs) from MS patients in their affinity for hMBP and in the ability of pIgGs to hydrolyze hBMP at different optimal pHs (3-10.5). IgGs containing lambda- and kappa-types of light chains demonstrated comparable relative activities in the hydrolysis of hMBP. IgGs of IgG1-IgG4 sub-classes were analyzed for catalytic activity. IgGs of all four sub-classes were catalytically active, with their contribution to the total activity of Abzs in the hydrolysis of hMBP and its 19-mer oligopeptide increasing in the order: IgG1 (1.5-2.1%) < IgG2 (4.9-12.8%) < IgG3 (14.7-25.0%) < IgG4 (71-78%). Our findings suggest that the immune systems of individual MS patients generate a variety of anti-hMBP abzymes with different catalytic properties, which can attack hMBP of myelin-proteolipid shell of axons, playing an important role in MS pathogenesis.
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Novosibirsk, Russia.
Galina A
GA
Legostaeva
Dar'ya I
DI
Polosukhina
Anna M
AM
Bezuglova
Boris M
BM
Doronin
Valentina N
VN
Buneva
Georgy A
GA
Nevinsky
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000378:metabolism; D055162:Biocatalysis; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D055815:Young Adult
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D010447:Peptide Hydrolases