IgA1 desialylated by microbial neuraminidase forms immune complex with naturally occurring anti-T antibody in human serum.
IgA1 was identified as the most prominent O-glycosylated protein of human serum. Desialylation by bacterial (Clostridium perfringens) neuraminidase rendered dot-blotted IgA1 recognizable by the naturally occurring serum antibody (anti-T) directed against Thomsen-Friedenreich antigen, Galbeta1-->3GalNAc-alpha-. On Western blot of serum O-glycosylated proteins anti-T recognized nearly all the bands including IgA1 as did the T antigen-specific animal lectin galectin-1 but only after their desialylation. Agglutination of desialylated human erythrocytes by anti-T was effectively inhibited by desialylated IgA1, but not by native IgA1 or other immunoglobulins. Desialylation of serum by neuraminidase led to significantly increased formation of immune complexes containing IgM, the major immunoglobulin type in anti-T on one hand and O-glycosylated proteins/IgA1 on the other. In further evidence for anti-T-desialylated IgA1 immune complex formation, purified anti-T added to desialylated, but not native serum led to formation of additional IgA-IgM immune complexes. Also neuraminidase treatment significantly reduced the titre of free (non-immune complexed) anti-T in serum, while selective removal of anti-T by affinity absorption resulted in considerable decrease in the amount of IgA1 that got converted to immune complexes following enzymatic desialylation of serum. Formation of immune complex between anti-T and neuraminidase-treated IgA1 in serum may be significant since many disease pathogens release neuraminidase and since IgA1 is a powerful ligand for tissue galectin-1 more so after desialylation. Diabetes also raises serum IgA and neuraminidase levels.
Biochemistry Department, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India.
Anuradha
N
N
Jayakumari
P S
PS
Appukuttan
D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D003016:Clostridium perfringens; D037483:Galectin 1 / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology*; D009439:Neuraminidase / Q000378:metabolism*
D000906:Antibodies; D000936:Antigen-Antibody Complex; D015295:Antigens, Tumor-Associated, Carbohydrate; D037483:Galectin 1; D007070:Immunoglobulin A; C016467:Thomsen-Friedenreich antigen; D009439:Neuraminidase