The researchers performed PCR-based genotyping on banked samples from 164 men enrolled in the Multicenter AIDS Cohort Study (MACS), including 55 who were HIV-infected and developed cryptococcal disease, a control group of 54 who were HIV-infected and 55 who were HIV-uninfected. After correcting for a number of factors like demographics and T cell counts, they found a strong association between the gene for the high-affinity FCGR3A 158V allele and the risk of cryptococcal disease in HIV-infected men.
To figure out what that meant, they followed up with binding studies and showed that cells that express FCGR3A 158V bind more strongly to antibody-C. neoformans complexes. Greater affinity for the antibody-C. neoformans complex could increase the attachment of the fungus to monocytes or macrophages, which could in turn increase the numbers of fungi living and replicating inside immune cells. And there's also the possibility that these infected immune cells could act like a Trojan horse, delivering C. neoformans cells across the blood-brain barrier and allowing them to infect the brain. Pirofski says these possibilities are now under investigation.
C. neoformans is found all over the environment and studies show that nearly everyone is exposed to the fungus during their lifetime. However, the organism rarely causes disease in healthy people, but strikes most often in people with weakened immune systems. It is the main cause of fungal meningitis in people living with HIV, and causes devastating disease in those with profound CD4+ T cell deficiency.
But not everyone with serious T cell deficiency develops cryptococcosis, and there is currently no way of knowing which patients will develop disease. Pirofski says a test that could distinguish wh
|Contact: Jim Sliwa|
American Society for Microbiology