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Gene makes some HIV-infected patients more at risk for fungal disease
Date:8/26/2013

HIV-infected people who carry a gene for a specific protein face a 20-fold greater risk of contracting cryptococcal disease, according to a study published in mBio, the online open-access journal of the American Society for Microbiology.

Cryptococcus neoformans is the most common cause of fungal meningitis among HIV-infected individuals. While the disease is a risk for everyone with HIV who has a very low level of CD4+ T cells, researchers have discovered that those with the gene for the protein FCGR3A 158V have an immune cell receptor that binds tightly to antibody-bound C. neoformans. Perversely, this tight binding by a vigilant immune system may mean the patient's own immune system strength becomes a weakness when facing the fungus.

"We found that this high affinity Fc receptor polymorphism was very highly overrepresented in the patients that got cryptococcal disease," says corresponding author Liise-anne Pirofski of the Albert Einstein College of Medicine & Montefiore Medical Center in The Bronx, New York. Patients with two copies of the high affinity Fc receptor gene had an almost 20-fold increased risk of contracting the disease.

"It's surprising that a receptor involved with a higher capacity to bind immune complexes would be associated with susceptibility in patients with HIV," says Pirofski, since phagocytosis of immune complexes is thought of as a mechanism for fighting invading microorganisms.

Differences among Fc gamma receptors (FCGR) have already been linked to cryptococcosis susceptibility among people who are not infected with HIV, but this new information sheds light on how these receptors could influence susceptibility in HIV patients, who are at elevated risk of developing cryptococcosis and are known to have high levels of antibodies to C. neoformans. FCGRs are proteins expressed on the outsides of different kinds of immune cells, including B lymphocytes, natural killer cells
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Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology
Source:Eurekalert

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