IgGs containing light chains of the λ- and κ- type and of all subclasses (IgG1-IgG4) from the sera of patients with systemic lupus erythematosus hydrolyze myelin basic protein.
Human myelin basic protein (hMBP)-hydrolyzing activity was recently shown to be an intrinsic property of antibodies from systemic lupus erythematosus (SLE) patients. Here, we present the first evidence demonstrating a significant diversity of different fractions of polyclonal IgGs (pIgGs) from SLE patients in their affinity for hMBP and in the ability of pIgGs to hydrolyze hMBP at different optimal pH values (5.3-9.5); the pH profiles of IgG1, IgG2, IgG3 and IgG4 were unique. IgGs containing the λ-type of light chains demonstrated higher relative activities (RAs) in the hydrolysis of hMBP and its oligopeptides (OPs) than κ-IgGs. IgGs of all four subclasses were catalytically active; their RAs in the hydrolysis of hMBP increased in the following order: IgG4 < IgG2 < IgG3 < IgG1. Metal-dependent proteolytic activity of λ-IgG, IgG1, IgG2 and IgG3 was higher than their serine protease-like activity, while these activities of κ-IgG were comparable. Phenylmethylsulfonylfluoride had almost no effect on the activity of IgG4, while EDTA significantly suppressed its activity. The RAs of λ-IgG in the hydrolysis of four OPs corresponding to different cleavage sites of hMBP were remarkably higher than those for κ-IgGs. IgG1-IgG4 demonstrated different RAs and patterns of hydrolysis of these four OPs. Although combination of Ca²⁺ plus Mg²⁺ was the best in the activation of IgG1 and IgG2, IgG3 and IgG4 demonstrated the highest activity in the presence of Ca²⁺ plus Co²⁺. The ratio of the RAs of λ-IgG, κ-IgG and IgG1-IgG4 preparations in all analyzed cases was individual for each preparation.
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Medical Academy of Sciences, Novosibirsk, Russia.
Anna M
AM
Bezuglova
Ludmila P
LP
Konenkova
Valentina N
VN
Buneva
Georgy A
GA
Nevinsky
D000328:Adult; D017151:Antibodies, Catalytic; D004492:Edetic Acid / Q000378:metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism*; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008670:Metals / Q000737:chemistry; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism*; D010664:Phenylmethylsulfonyl Fluoride / Q000378:metabolism; D059748:Proteolysis; D057057:Serine Proteases / Q000378:metabolism
D017151:Antibodies, Catalytic; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D008670:Metals; D004676:Myelin Basic Protein; D010664:Phenylmethylsulfonyl Fluoride; D004492:Edetic Acid; D057057:Serine Proteases