Evaluation of immunoglobulin A1 (IgA1) protease and IgA1 protease-inhibitory activity in human female genital infection with Neisseria gonorrhoeae

Immunoglobulin A1 (IgA1) protease, an enzyme that selectively cleaves human IgA1, may be a virulence factor far pathogenic organisms such as Neisseria gonorrhoeae. East protection from the effects of IgA1 protease includes an tibody-mediated inhibition of IgA1 protease activity, and it is believed th at the relative balance between IgA1 protease and inhibitory antibodies con tributes to the pathogenesis of disease caused by IgA1. protease-producing organisms. We have examined the levels of these two opposing factors in gen ital tract secretions and sera from women with uncomplicated infection with N. gonorrhoeae. When IgA1 in cervical mucus was examined by Western blotti ng, no evidence of cleavage fragments characteristic of IgA1 protease activ ity was seen in gonococcus-infected or control patients. Cleavage fragments typical of IgA1 protease were detected, however, after the addition of exo genous IgA1 protease to cervical mucus. Degraded IgA1 was detected in some vaginal wash samples, but the fragment pattern was not typical of IgA1 prot ease activity. All N. gonorrhoeae isolates from the infected patients produ ced IgA1 protease in vitro. All but two serum samples and 16 of 65 cervical mucus samples displayed inhibitory activity against gonococcal IgA1 protea se, but there was no significant difference in the level of inhibitory acti vity between gonococcus-infected and noninfected patients in either cervica l mucus or serum. There was no difference in the levels of IgA1 protease-in hibitory activity in serum or cervical mucus collected from patients at rec ruitment and 2 weeks later. These results suggest that cleavage of IgA1 by gonococcal IgA1 protease within the lumen of the female lower genital tract is unlikely to be a significant factor in the pathogenesis of infections b y N. gonorrhoeae.