IgA is the principal carrier of antibody activity in external secretions and is more resistant to degradation by common proteases than other classes of immunoglobulins. IgA has been shown to be involved in the protection of mucosal surfaces from infection and has been implicated in immunity to dental caries and may be involved in protection against forms of periodontal disease. IgA occurs in two subclasses, IgA1 and IgA2, and two molecular forms, monomer and polymer, which have unique distributions in serum and secretions. The IgA1 subclass (but not the IgA2 subclass) is susceptible to cleavage by highly specific microbial proteases whose only known substrate is human IgA1. Recent findings indicate that natural antibodies to certain antigens of Streptococcus mutans, the principal etiologic agent of dental caries, occur predominantly in the IgA1 subclass, while others occur predominantly in IgA2. It has also been found that ratios of IgA1/IgA2 may change during an active infection. The long term objectives of this application are to approach questions concerning the potential of IgA1 proteases to compromise IgA- mediated immunity. The subclass distribution of specific antibodies that occur in patients with localized juvenile periodontitis (LJP) and active caries by examining them before and at periods after treatment. The IgA subclass distribution of specific antibodies in parotid saliva will be determined for selected antigens of S. mutans and the principal suspected pathogen of LJP, Actinobacillus actinomycetemcomitans. Serum IgA antibodies will also be examined in LJP patients for subclass distribution and for polymer/monomer distribution, using high performance liquid chromatography, as a means of discovering their origin. A solid phase assay will be developed which will allow for rapid enumeration of IgA protease-producing colonies in microbial samples. Knowledge of the dynamics of the IgA subclass response in disease together with a means of enumeration of IgA1 protease producing microorganisms will lead to a greater understanding of the potential impact of proteases on IgA- mediated immunity.
