Hydrolysis of myelin basic protein by IgM and IgA antibodies from the sera of patients with multiple sclerosis.
BACKGROUND
The presence of abzymes (Abzs) in human sera is a specific feature 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-hydrolyzing MS IgMs and IgAs in patients with MS has not been studied.


METHODS
Homogeneous IgM and IgA fractions were isolated from human sera by affinity chromatography on different adsorbents. The Ab-dependent hydrolysis of hMBP was analyzed using SDS-PAGE.


RESULTS
We present evidence showing that MS IgMs and IgAs (but not Abs from the sera of healthy individuals) catalyze the hydrolysis of hMBP. Specific enzymatic activities of IgMs and sIgAs from sera of any single patient were usually significantly higher than those of IgGs. Specific inhibitors of acidic and thiol proteases demonstrated a weak effect on proteolytic activity 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 pig MBP but not many other tested proteins. Although the biological function of this proteolytic activity is 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 polyclonal IgGs, IgMs, and IgAs with different proteolytic properties, which hydrolyze MBP, the major protein component of the myelin-proteolipid shell of axons and a well-known MS autoantigen.
Polosukhina
Dar'ya I
DI
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia.
Buneva
Valentina N
VN
Doronin
Boris M
BM
Tyshkevich
Olga B
OB
Boiko
Alexey N
AN
Gusev
Evgenii I
EI
Favorova
Olga O
OO
Nevinsky
Gregory A
GA
D000293:Adolescent; D000328:Adult; D000818:Animals; D002850:Chromatography, Gel; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism*; D013552:Swine
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D004676:Myelin Basic Protein