Loss of antibody activity in human immunoglobulin A exposed extracellular immunoglobulin A proteases of Neisseria gonorrhoeae and Streptococcus sanguis.
Immunoglobulin A (IgA) proteases are extracellular enzymes elaborated by Neisseria gonorrhoeae, N. meningitidis, and Streptococcus sanguis. These enzymes each cleave human IgA1 at a critically situated prolyl-threonyl peptide bond to yield Fab alpha and Fc alpha fragments. To study their effect on the antibody activity of human IgA, we enzymatically digested a group of five human IgA monoclonal immunoglobulins with high-titer rheumatoid factor or cold agglutinin activity and human serum macroamylase, an amylase-IgA complex. In contrast to four control IgM rheumatoid factor monoclonal proteins, whose activity was unaffected by enzyme, gonococcal and streptococcal IgA proteases caused prompt, major reductions of IgA antibody activity to negligible levels and converted macroamylase activity to amylase of normal size, as determined by molecular sieve chromatography. In addition, both enzymes promptly deagglutinated sensitized cells that had been aggregated by IgA rheumatoid factors, indicating that IgA bound to antigen is also susceptible to enzyme cleavage. Fab fragments of Iga protein Chr, a rheumatoid factor, showed essentially no antigen-binding activity despite the high titers observed with the parent protein. These studies emphasize the high degree of specificity of the microbial proteases for IgA and their potential for interfering with antibody activity in the IgA1 subclass.
D000371:Agglutination / Q000187:drug effects*; D000681:Amylases / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007075:Immunoglobulin M / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000494:pharmacology*; D012217:Rheumatoid Factor; D013298:Streptococcus sanguis / Q000201:enzymology*
D007070:Immunoglobulin A; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007075:Immunoglobulin M; D012217:Rheumatoid Factor; D000681:Amylases; D010447:Peptide Hydrolases