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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-seven strains of the genus Haemophilus and five strains of Streptococcus pneumoniae were examined for their ability to produce extracellular enzyme that cleaves immunoglobulin molecules. All strains of H. influenzae, H. aegyptius, and S. pneumoniae elaborated enzyme that selectively cleaved human immunoglobulin A1 (IgA1) myeloma proteins but was inactive against a variety of other proteins including human IgA2, IgG, and IgM, porcine and bovine secretory IgA, human and bovine serum albumins, and ovalbumin. Although susceptible, human secretory IgA remained largely undigested. Two strains of H. pleuropneumoniae isolated from fatally infected pigs cleaved porcine secretory IgA, but had no effect on human IgA proteins. None of 16 strains that belonged to nonpathogenic Haemophilus species produced IgA protease. Analyses of the cleavage products of human IgA1 and secretory IgA proteins by immunochemical methods, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and analytical ultracentrifugation revealed that Fab and Fc fragments were produced. Since the production of IgA1 protease by Neisseria meningitidis has been reported previously, our finding that H. influenzae and S. pneumoniae produce an IgA1 protease indicates that this is a property of all three major etiological agents of bacterial meningitis. This suggests that IgA1 protease production may be an important factor in the pathogenesis of this disease.
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PMID:Pathogenic species of the genus Haemophilus and Streptococcus pneumoniae produce immunoglobulin A1 protease. 4 Aug 78

Bacterial strains of Haemophilus species and Streptococcus pneumoniae were examined for synthesis of the enzyme immunoglobulin A1 (IgA1) protease. Of 36 H. influenzae strains examined, 35 produced IgA1 protease; strains included all six capsular types, unencapsulated variants of types b and d, and untypable H. influenzae. Eight Haemophilus strains (non-H. influenzae) were studied, and two produced IgA1 protease. All 10 strains of S. pneumoniae produced IgA1 protease; these strains included 9 different capsular polysaccharide types and 1 untypable strain. Both IgA1 proteases cleaved myeloma IgA1 and secretory IgA but not myeloma IgA2, IgM, or IgG as determined by immunoelectrophoresis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that both enzymes cleaved IgA1 myeloma sera, but not IgA2, into two fragments. The apparent molecular weight of the cleaved fragments was dependent both on the apparent molecular weight of the cleaved fragments was dependent both on the specific IgA1 protease assayed and the specific IgA1 substrate utilized. It is postulated that both carbohydrate variation between the IgA1 substrates studied and the ability of S. pneumoniae glycosidases to cleave carbohydrates from glycoprotein offer an explanation for the different fragment sizes observed.
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PMID:Immunoglobulin A1 protease production by Haemophilus influenzae and Streptococcus pneumoniae. 4 Aug 80

IgA protease is a proteolytic enzyme found in whole human saliva and in dental plaque that cleaves both secretory and myeloma IgA of human origin to yield intact Fabalpha and Fcalpha fragments. To determine which bacteria are capable of producing this enzyme, we have examined a variety of strains normally found in the human oral cavity and a number of streptococci of known Lancefield group serotype. Streptococci of groups A, B, C, D, F, G, H, M, and N, Streptococcus mutans, Streptococcus sanguis, Streptococcus mitior, Streptococcus salivarius, Streptococcus faecalis, Veillonella, Lactobacillus, Actinomyces, Propionibacterium, Bacteroides, and Fusobacterium were grown in liquid medium, and fluids were examined for IgA protease activity. Only S. sanguis and clinically isolated group H streptococci elaborated IgA protease under the culture conditions used. Negative strains could not be stimulated to produce the enzyme when cultured in the presence of secretory IgA. Among the natural oral bacteria, capacity to produce IgA protease is restricted to certain species of Streptococcus, notably those of the group H serotype. Since secretory immunity is mediated by the IgA class of antibody, the presence of this enzyme at mucosal surfaces could modify the secretory immune function.
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PMID:Evaluation of human oral organisms and pathogenic Streptococcus for production of IgA protease. 116 76

We used an immunofluorescent sequential-saturation-of-antibody assay and an interactive computer program for Scatchard analysis to determine association constants (Ka) of 33 murine monoclonal antibodies (Mabs) specific for human IgA epitopes. Ka ranged from 0.37 to 690 x 10(7) liters per mole (an approximate 1900-fold difference). Specificity was validated with a panel of 18 highly purified IgA1 and IgA2 myeloma proteins and secretory IgA using an immunofluorometric assay. Western blots of bacterial IgA protease digests were used to locate the epitopes of IgA specific Mabs in either the Fab, Fc, or hinge region. Mabs specific for unique epitopes on secretory IgA or free secretory component (FSC) were produced and evaluated.
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PMID:Specificity and association constants of 33 monoclonal antibodies to human IgA epitopes. 247 39

The interaction of human IgA antibodies with the classical pathway of complement activation was investigated in a homologous human system, by means of two IgA1 and three IgG1 myeloma proteins having antibody activity against a defined antigen, staphylococcal alpha-toxin. In a solid-phase antigen-dependent C3b-binding ELISA system, the monoclonal IgG antibodies were previously shown to activate the classical complement pathway synergistically, resembling polyclonal IgG antibodies, whereas IgA antibodies were unable to activate complement by either pathway. In the present study, IgA antibodies were found to inhibit significantly the activation of complement initiated by antigen-bound polyclonal or mixed monoclonal IgG antibodies, in relation to the amount of IgA antibodies applied and bound to antigen. IgA1 myeloma proteins devoid of antigen-binding activity were without effect. Inhibition was independent of the ability of the IgA antibodies to compete against the IgG antibodies in binding to antigen, and was demonstrable with physiological concentrations of antibodies. Similar results were obtained with polyclonal serum IgA having antigen-binding activity. However, the binding of C1q to antigen-complexed IgG was inhibited only by a monoclonal IgA antibody that could compete against one of the three monoclonal IgG antibodies that bound C1q synergistically. This observation implied that at least two mechanisms were involved in the inhibition of C3b fixation. Fab alpha fragments of monoclonal IgA antibodies, obtained by cleavage with IgA1 protease from Haemophilus influenzae type b, were found to have a similar inhibitory effect on C3b fixation to the intact IgA1 antibodies. This observation supports the hypothesis that IgA1 proteases contribute to the invasive pathogenicity of certain mucosal bacteria, by cleaving secretory IgA1 antibodies to antigen-binding Fab alpha fragments, which are not only defective in mucosal defense properties, but which also protect the organisms from other immune effector systems, such as complement activation.
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PMID:Anti-inflammatory activity of human IgA antibodies and their Fab alpha fragments: inhibition of IgG-mediated complement activation. 260 39

Monoclonal IgA paraproteins of subclasses 1 and 2, isolated from the sera of myeloma patients, were incubated for 4, 24, 48 and 72 hours with B. pertussis, B. parapertussis, B. bronchiseptica cultures, as well as Haemophilus influenzae strain. The fragmentation of IgA was studied by immunielectrophoresis with antisera to alpha-chain, to Fab alpha + Fc alpha, to Fab alpha and with antisera to light chains corresponding to the type of paraprotein. B. pertussis and B. parapertussis were found to have subclass-unspecific IgA protease which splitted off a cathode fragment, similar to Fab-fragment and, probably, corresponding to the variable domain of alpha-chain (Fv), after 48-hour incubation. Similar IgA protease was detected in H. influenzae, found to have classical IgA1 protease as well. All Bordetella species under study splitted off anode components from IgA paraproteins of both subclasses. These components, containing the determinants of heavy and light IgA chains, were either IgA - alpha I-antitrypsin complexes or some IgA fragments with high electrophoretic motility. None of the strains under study splitted monoclonal IgG.
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PMID:[IgA protease activity of microbes in the genus Bordetella]. 286 69

Serum samples from 26 normal volunteers were evaluated by isotype-specific ELISA for the presence of IgG and IgM antibodies directed at IgA. Although there were wide variations in antibody levels, anti-IgA antibodies of both isotypes were found in all individuals tested. The anti-IgA activity was detected against a variety of polymeric and monomeric IgA1 and IgA2 myeloma proteins containing both kappa and lambda light chains. By using Fab and Fc fragments generated by incubation of an IgA1 myeloma protein with IgA1 protease, it was shown that the anti-IgA activity was specific for the Fab portion of the IgA molecule. It was also demonstrated that the serum of two individuals contained both IgG and IgM activity directed at autologous affinity-purified IgA. IgM antibody levels against both whole IgA and Fab of IgA were significantly higher than IgG antibody levels. Cells producing anti-IgA antibodies of both isotypes were detected in lipopolysaccharide-stimulated human spleen.
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PMID:Normal human sera contain antibodies directed at Fab of IgA. 349 62

Immunoglobulin A1 (IgA1) proteases may be important virulence factors of certain bacteria involved in the pathogenesis of meningitis, gonorrhea, destructive periodontal diseases, and some other infections affecting mucosal membranes. This study evaluated the antigen-binding activity of free Fab alpha fragments released from human myeloma IgA1 by IgA1 protease from Haemophilus influenzae. Six myeloma proteins with antibody activity against streptolysin O, alpha-staphylolysin, or streptococcal hyaluronidase were used. Complete cleavage of the IgA1 myeloma proteins in the hinge region of the heavy chain did not affect their antigen-binding capacity. The titers of neutralizing activity associated with free Fab alpha fragments were not significantly different from those of the intact IgA1 proteins. The retained antigen-binding capacity of cleaved IgA1 is an important factor in the understanding of how IgA1 proteases may interfere with the immune protection of mucosal membranes.
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PMID:Retained antigen-binding activity of Fab alpha fragments of human monoclonal immunoglobulin A1 (IgA1) cleaved by IgA1 protease. 351 53

IgA protease, a proteolytic enzyme found in human saliva and colonic fluid, hydrolyzes human serum IgA immunoglobulins to yield Fab(alpha) and Fc(alpha) fragments. The enzyme is produced by organisms in the normal human microflora and can be purified from culture filtrates of the common human oral organism Streptococcus sanguis (American Type Culture Collection no. 10556). IgA protease is inactive against all other protein substrates examined including the other classes of human immunoglobulins. The role of this enzyme in affecting the function of the secretory IgA immune system is unknown. To further characterize and explain this unusual substrate specificity, the susceptibility of 31 human IgA myeloma proteins of both subclasses was investigated. 16 IgA1 and 15 IgA2 myeloma paraproteins were treated with enzyme and the extent of proteolysis was determined by cellulose actate electrophoresis, immunoelectrophoresis, polyacrylamide gel electrophoresis, and column chromatography. All IgA1 proteins were enzymatically cleaved to Fab(alpha) and Fc(alpha) fragments, but all IgA2 proteins were resistant, yielding no fragments after prolonged enzymatic treatment. N-terminal amino acid sequence analysis of the purified Fc(alpha) fragment of a single IgA1 paraprotein was as follows: Thr-Pro-Ser-Pro-?-Thr-Pro-Pro-Thr-Pro-Ser-Pro-Ser. Comparison of this sequence to that reported for the IgA1 heavy chain shows that the enzyme-susceptible peptide bond is a Pro-Thr in the IgA1 hinge region. The most likely explanation of the resistance of the IgA2 subclass to IgA protease is a deletion in the heavy chain which commences with the critical threonine of the susceptible Pro-Thr bond.
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PMID:Differential susceptibility of human IgA immunoglobulins to streptococcal IgA protease. 443 34

Protein A-binding fractions of two IgA1 myeloma proteins failed to produce Fc fragments on digestion with IgA1 protease from Streptococcus sanguis. A polymeric protein A-binding IgA1 fraction yielded a protein A-non-binding monomer, which was further cleaved into Fab fragments but it did not yield Fc fragments. The protein A-binding fraction of a monomeric IgA1 yielded an IgA molecule lacking one Fab fragment. Subsequently, the remaining part of its cleaved alpha chain was degraded. Further digestion yielded Fab but not Fc fragments. Similarly, F(abc)2 and Fabc fragments, which lack the CH3 domain (8), yielded Fab fragments but not CH2 domains. Thus, the enzyme in addition to cleaving IgA in the hinge region, under certain conditions, also degrades its Fc fragments.
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PMID:Cleavage of protein A-binding IgA1 with IgA1 protease from Streptococcus sanguis. 635


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