Bacterial degradation of immunoglobulin A1 in relation to periodontal diseases.
Periodontal diseases affect millions of people world wide. Prevention and treatment of these diseases require considerable attention from the individual as well as society and cause great expenses. Understanding disease etiology and mechanisms of pathogenesis is a prerequisite for optimal treatment strategies. The highly variable speed of periodontal destruction and in some sites persistence for years of deep pockets without further periodontal destruction points to the significance of individual bacterial species in the complex subgingival microflora for pathogenesis. Destruction of periodontal tissue occurs when the load of bacterial virulence factors overcomes the local immune defense. One way of doing this is by bacterially-induced degradation of IgA which is considered to mediate its protective functions in an anti-inflammatory way and to down-regulate inflammation through inhibition of IgG- and IgM-mediated activities. A competent IgA system may be of particular significance in chronic inflammatory diseases, as periodontal diseases, where the inflammatory reaction in itself probably is the main cause of destruction. In these cases, degradation of IgA may serve the purpose of immune evasion for the bacteria and at the same time may induce a relatively increased activity in the inflammation-stimulating part of the immune system which may aggravate periodontal destruction. Both gram-positive rods, streptococci, and Veillonella species from the subgingival microflora induce an altered immunoelectrophoretic mobility of IgA1 indicative of removal of terminally positioned sialic acid. Quantitative determination of residual carbohydrate content of IgA1 after incubation with bacterial cells of Gram-positive rods has confirmed that they remove sialic acid, and in addition to that, only minor amounts of carbohydrates. Apart from serving a nutritional purpose, desialylation of IgA may also serve a purpose of immune evasion. Glycosylation and, in particular sialic acid protects glycoproteins, including immunoglobulins, against proteolytic enzymes and deglycosylation of antibodies increase their sensitivity to proteolytic degradation and inhibit the Fc-mediated effector functions that mediate antigen disposal. Extensive proteolytic degradation of IgA1 is induced by a number of bacterial species often associated with periodontal diseases, including P. gingivalis, Pr. intermedia, and Pr. nigrescens. These species produce enzymes of broad proteolytic activity, that also may degrade immunoglobulins of other isotopes, complement factors, iron-containing plasma proteins etc. Extensive hydrolysis of immunoglobulins induced by these bacteria serve a nutritional purpose and is essential for growth of other bacteria in mixed cultures. It also has an obvious detrimental effect on the defence potential of the specific humoral immune system. These bacteria seem to be essential for the transmissibility of experimental infections in animals with mixtures of oral bacteria and a likely reason is their ability to provide the other bacteria with amino acids, peptides, and iron for growth and their ability to inhibit the immune defence. The hinge region of IgA1 is relatively resistant to proteolysis because of a high proline content and presence of several oligosaccharide side chains. It is therefore interesting that a number of taxonomically unrelated bacteria, including both commensals and overt pathogens, have evolved the capability to specifically cleave human IgA1 in the hinge region. These so-called IgA1 proteases leave Fab and Fc fragments intact for which reason a direct nutritional purpose of the enzymes may be excluded. In the oral cavity, specific IgA1 proteases are produced by the streptococcal species that constitute a considerable proportion of initial dental plaque and the flora on buccal and pharyngeal mucosa. In all three cases the flora is sparse and contact with saliva, including S-IgA1 antibodies is intimate. (ABSTRACT TRUNCATED)
Grønbaek Frandsen
E V
EV
Royal Dental College, Faculty of Health Sciences, University of Aarhus, Denmark.
D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D008969:Molecular Sequence Data; D009055:Mouth / Q000382:microbiology*; D010510:Periodontal Diseases / Q000209:etiology*; D012697:Serine Endopeptidases / Q000378:metabolism
D007070:Immunoglobulin A; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase