Researchers at the University Hospital of Ulm, Germany, identified the mechanism by which an anti-TNF therapy impairs host defense against tuberculosis.

Anti-TNF therapies, which target the protein TNF, have improved the lives of many with inflammatory diseases such as rheumatoid arthritis. However, the treatment has been known to leave these patients with a decreased ability of the immune system to fight infections and has been associated with an increased incidence of TB.

Steffen Stenger and colleagues made the discovery by studying the immune cells of patients before and after treatment with the anti-TNF therapy infliximab,

In the study, a subset of CD8-expressing effector memory immune T-cells characterized by expression of the proteins CD45RA and granulysin (which the authors termed CD45RA+ effector memory CD8+ T cells) were identified as having a major role in targeting the bacterium that causes TB, mycobacterium tuberculosis (M. tuberculosis). Additionally, the numbers of CD45RA+ effector memory CD8+ T cells were reduced in patients following treatment with infliximab. As this correlated with a decreased ability of peripheral blood from the patients to kill M. tuberculosis, the authors conclude that the loss of this immune cell subset provides a mechanism to explain the reactivation of latent tuberculosis infection in some individuals being treated with infliximab.

The study appears in the Journal of Clinical Investigation, and is accompanied by commentary, Anti-TNF immunotherapy and tuberculosis reactivation: another mechanism revealed, from Joel Ernst, MD, of the New York University School of Medicine, New York. Ernst discusses the clinical importance of these data and highlights some of the possibilities that they raise.