June 16, 2009

B Cell Test Predicts Who Will Get Meningitis

A newly devised test of the immune system’s response to Cryptococcus neoformans—a fungal infection common among people with advanced HIV disease—is a strong predictor of who is most at risk for developing one of its more serious complications: a potentially lethal brain illness known as meningitis. A study published online June 15 in The Journal of Infectious Diseases documents this predictive potential and says that the test could help providers determine who would benefit most from taking antifungal drugs to prevent meningitis.

Combination antiretroviral therapy has reduced the chance that a person living with HIV in the United States will come down with cryptococcal meningitis to about 2 percent each year. However, the disease remains a significant cause of death in developing nations, with nearly 600,000 people developing the disease globally every year. Most cases occur in people with CD4 counts of 50 copies or less. Because the C. neoformans fungus is so widespread, and since most people who become infected with it do not develop meningitis, Krishanthi Subramaniam, PhD, and her colleagues wondered whether it would be possible to predict more accurately who is most at risk for developing the disease.

Sumbramaniam, from the Albert Einstein College of Medicine and Montefiore Medical Center in the Bronx, New York, and her team examined a type of memory B cell known as IgM+ cells in HIV-positive and HIV-negative patients. These B cells are known to respond to infections such as C. neoformans. The team examined the cells in 29 HIV-positive patients with a history of meningitis, and 30 HIV-positive and 20 HIV-negative patients without a history of meningitis. HIV-positive patients with a history of meningitis had an average lowest-ever CD4 count of 41, compared with 221 CD4 cells in HIV-positive patients with no history of meningitis.

Subramaniam and her colleagues found that HIV-positive patients with a history of meningitis had far fewer IgM+ cells than HIV-positive patients with no history of meningitis. To rule out the possibility that developing meningitis caused low IgM+ numbers, the team tested stored blood samples collected before people developed meningitis. They found that IgM+ levels were still low before the patients developed meningitis  and that meningitis was highly likely when the percentage of B cells expressing IgM+ dropped below 50 percent.

The authors conclude that preventive treatment for meningitis, which is not currently recommended for most patients, could be targeted to people with fewer than 50 CD4 cells who also have low IgM+ levels.

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