M-1850. IgM Memory B-cells as a Novel Risk Factor for Cryptococcal Disease in HIV-infected Patients
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.
Alice Guh, MD, Centers for Disease Control and Prevention, Atlanta, GA, Brian Metzger, MD MPH, Montefiore Medical Center, New York, NY, Kris Subramaniam, Albert Einstein College of Medicine, Lawrence Hanau, Montefiore Medical Center, Liise-anne Pirofski, MD, FIDSA and  B. S. Metzger, None.

A. Danielle Iuliano is an Epidemic Intelligence Officer at the Centers for Disease Control and Prevention. She graduated with a PhD in Infectious Disease Epidemiology from the University of Pittsburgh, Graduate School of Public Health in 2008. Additionally, she earned a Certificate in Public Health Preparedness and Disaster Response. She earned a Masters in Public Health from Rollins School of Public Health, Emory University in 2002. She has a BA in Psychology and Sociology from Emory University, 2000.

Dr. Pirofski earned her BA at UC Berkeley and her MD from Albert Einstein College of Medicine. She did her residency in internal medicine at Bellevue Hospital and NYU Medical Center and her fellowship in infectious diseases and post-doctoral training at Albert Einstein College of Medicine. She is professor of Medicine, Microbiology and Immunology and the Selma and Jacques Mitrani Professor of Biomedical Research at the Albert Einstein College of Medicine. Since 2007, Dr. Pirofski has been Chief of the Division of Infectious Diseases in the Department of Medicine at the Albert Einstein College of Medicine and Montefiore Medical Center. Her research program is focused on immunity to fungi and encapsulated pathogens, with a particular interest in vaccines, antibody and B cell immunity, and mechanisms of host immunomodulation that balance beneficial and detrimental inflammation. Dr. Pirofski is also co-developer of the Damage-response framework of microbial pathogenesis, an integrated theory that incorporates the contributions of the host and the microbe into the outcome of microbial infection. Dr. Pirofski is a member of the American Academy of Microbiology and a Fellow of the Infectious Diseases Society of America. She is an associate editor of the journal Medical Mycology and currently, a branch lecturer for the American Society for Microbiology and a standing member of the Vaccines for Microbial Diseases study section of the National Institutes of Health.

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