August 28, 2013

Gene makes some HIV-infected patients more at risk for fungal disease

blogger_HIVWASHINGTON, DC – August 27, 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.

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