Resistance of normal serum IgA and secretory IgA to bacterial IgA proteases: evidence for the presence of enzyme-neutralizing antibodies in both serum and secretory IgA, and also in serum IgG.
Normal serum IgA and secretory IgA (sIgA) of subclass IgA1 were isolated from pooled human serum and milk, respectively. They were tested for their susceptibility to bacterial IgA proteases from Haemophilus influenzae, Streptococcus pneumoniae, Neisseria gonorrhoeae, and Neisseria meningitidis that cleave IgA of only the IgA1 subclass. They were also tested for susceptibility to a novel IgA-protease from Clostridium ramosum that cleaves IgA of the IgA1 as well as the IgA2 subclass of the A2m(1) allotype. Both normal serum IgA1 and sIgA1 exhibited resistance to most IgA proteases. The one exception was the IgA protease from C. ramosum which readily cleaved both the serum IgA1 and sIgA1 into Fab and Fc fragments. Secretory component (SC) had nothing to do with the resistance of these IgAs. The resistance of these IgAs to most of the IgA proteases was found to be due to their enzyme-neutralizing antibody activity, since the Fab but not the Fc fragment of sIgA1 showed enzyme-inhibitory activity against these IgA proteases. Similar enzyme-neutralizing antibody activity was found in the pepsin-digested normal serum IgG-(Fab')2 fragment. These results indicate that the induction of the enzyme-neutralizing antibodies against the bacterial IgA proteases took place not only in mucosal sIgA but also in serum IgA and IgG. No enzyme-neutralizing antibody activity against the novel IgA-protease of C. ramosum was detected in any immunoglobulin preparations used in the present study or in the serum of a patient who carries the IgA protease-producing strain of C. ramosum in his feces.
D000937:Antigen-Antibody Reactions; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D003013:Clostridium / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006193:Haemophilus influenzae / Q000201:enzymology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D066298:In Vitro Techniques; D008895:Milk, Human / Q000276:immunology; D009344:Neisseria gonorrhoeae / Q000201:enzymology; D009345:Neisseria meningitidis / Q000201:enzymology; D010447:Peptide Hydrolases / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000201:enzymology
D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D010447:Peptide Hydrolases