Low Expression of Immune Response Gene Increases TB Risk

A genetic mutation in Africans with human immunodeficiency virus (HIV) has been identified that puts them at a much higher risk for tuberculosis (TB) infections.

Africans have some of the highest rates of TB in the world, and it has long been suspected that genetic susceptibility plays a role; however, establishing candidate genes across populations to gauge risk has remained a challenge.

Scientists at the Perelman School of Medicine (Philadelphia, PA, USA) isolated DNA from peripheral blood mononuclear cells (PBMC) pellets from 404 patients in a severe sepsis cohort recruited from hospitals in the Central Region of Uganda from July 2006 to May 2009. The patients with suspected infection, meeting criteria for severe sepsis, with portable whole-blood lactate concentration greater than 2.5 mmol/L were included. All patients were investigated with bacterial and mycobacterial blood cultures. The study database was queried for patient demographics, HIV status, and CD4 count, use of highly active antiretroviral therapy (HAART), where applicable, as well as results of blood cultures.

Automated capillary electrophoresis on a DNA sequencer was performed on the polymerase chain reaction (PCR) products, and the CATT alleles were identified using Genotyper version 3.7 software (Applied Biosystems; Foster City, CA, USA). The team found that found that a commonly occurring polymorphism in an immune response gene called macrophage migration inhibitory factor (MIF) confers almost a two-and-a-half fold increased risk for severe TB in patients from Uganda who were co-infected with HIV. These low-expressers of MIF were almost twice as common among people of African ancestry as Caucasians.

Rituparna Das, MD, PhD, the lead author, said, “These results help explain the increased incidence of TB among this group. Moreover, this is especially important in people co-infected with HIV, who have a compromised immune system and also constitute the major public health challenge of controlling TB. With the high degree of TB exposure in the community, we hope to identify which patients are more likely to go on to develop active TB disease, and in the future, target these patients for preventive therapies." The study was published on July 23, 2013, in the journal the Proceedings of the National Academy of Sciences of the United States of America (PNAS).

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Perelman School of Medicine
Applied Biosystems