Session: Slide Session: Clinical Mycology
Monday, October 27, 2008: 12:00 AM
Room: Room 145A
Background: IgM memory B-cell expression is reduced in diseases associated with an increased risk for cryptococcosis, including HIV infection, common variable immunodeficiency, and X-linked hyper IgM. IgM memory B-cells are required for host defense against other encapsulated microbes, but their role in resistance to Cryptococcus neoformans (CN) is unknown. Therefore, we investigated the hypothesis that IgM memory B-cells may contribute to host resistance of CN disease. Methods: Peripheral blood IgM memory B-cell expression was assessed in 29 HIV-infected individuals with a history of cryptococcal disease (HIV+CN+), and compared to 30 HIV-infected (HIV+CN-) and 20 HIV-uninfected (HIV-) subjects without a history of cryptococcal disease (cohort 1). We also analyzed banked, pre-disease samples from 8 HIV+ subjects who subsequently developed cryptococcal disease (HIV+CN+), and 8 HIV+ (HIV+CN-) subjects matched by CD4 T-cell levels and 15 HIV- age-matched subjects who did not develop disease, all enrolled in the Multicenter AIDS Cohort Study (cohort 2). Results: In cohort 1, HIV+CN+ cases had a lower percent expression of IgM memory B-cells than HIV+CN- (P<.01) and HIV- controls (P<.05). Comparing the HIV+CN+ and HIV+CN- subjects using multivariate logistic regression, CD4 nadir < 200 (OR=15.6, P=.01) and percent expression of IgM memory B-cells < 50% (OR=5.5, P=.03) remained significant predictors of cryptococcal disease while controlling for age, sex, race, and HIV viral load. In cohort 2, HIV+CN+ cases had a lower percent expression of IgM memory B-cells than HIV+CN- (P=.02) and HIV- controls (P<.01). For this cohort, percent expression of IgM memory B-cells < 38.5% was a significant predictor of cryptococcal disease (OR=14, P=.02). Conclusions: The percent expression of IgM memory B-cells is potentially a novel risk factor for HIV-associated cryptococcosis - one that may be able to identify patients for prophylaxis and/or immune modulation.