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Magnesium Supplements May Reduce Viral Infection in “XMEN” Patients

A new NIAID study suggests that magnesium supplements enhance antiviral immune responses and reduce the persistent Epstein-Barr virus (EBV) infections found in people with XMEN disease, a rare primary immune deficiency disease. The results appear in the July 12, 2013, online issue of Science.

Background

EBV-infected cell (green) expressing the ligand or signal (red) that activates NKG2D
An EBV-infected cell (green) expresses the ligand or signal (red) that activates NKG2D. Uninfected cells (blue only) do not express the ligand. Credit: Dr. Benjamin Chaigne-Delalande

In 2011, NIAID investigators led by Michael Lenardo, M.D., identified the genetic mutation causing XMEN (X-linked magnesium deficiency with EBV infection and neoplasia) disease. They discovered that XMEN patients have a mutation in the gene that codes for magnesium transporter 1 (MAGT1). MAGT1 brings magnesium inside immune cells to support their function. Because the immune cells of XMEN patients do not have enough magnesium, the cells cannot function normally to control infections like EBV.

In response to this discovery, the researchers were interested in 1) understanding how magnesium regulates antiviral immune responses and 2) testing whether magnesium supplements can improve the immune function and health of people with XMEN disease.

Results of Study

Dr. Lenardo, Benjamin Chaigne-Delalande, Ph.D., graduate student Feng-Yen Li, and their colleagues in the NIAID Laboratory of Immunology examined immune cells from seven XMEN patients, including three from the previous study. They discovered that the mutation compromised the function of CD8+ T cells and natural killer (NK) cells, which are important for identifying and killing tumor cells and infected cells.

In the laboratory, the researchers examined the patients’ CD8+ T cells and NK cells and found that adding magnesium restored function. They discovered that these cells did not express NKG2D, an important surface protein that alerts immune cells to problems like infection and cancer. Remarkably, adding magnesium boosted the expression of NKG2D, which explains the restored function of the patients’ immune cells.

With these promising laboratory results, the researchers then provided magnesium supplements, with careful monitoring, to XMEN patients. They subsequently observed higher levels of magnesium inside immune cells, increased expression of NKG2D, and lower numbers of EBV-infected cells. These effects were reversed when magnesium supplements were halted, indicating that continuous magnesium is required.

Significance

This study demonstrates that magnesium supplements may be an effective therapy for controlling EBV infection in XMEN patients. XMEN patients have a greater risk of cancer, and early development of cancer correlates with high levels of EBV. Thus, magnesium therapy may prevent cancer progression in XMEN patients.

This study also establishes a link between NKG2D and control of EBV infection. Because chronic EBV infections afflict patients of other disorders, this information may be useful for designing general therapies against EBV.

Next Steps

The investigators are developing a clinical protocol to study magnesium supplementation in more XMEN patients. They also will examine the function of other human magnesium transporters, which are not well-characterized and may play important roles in immune cells. They plan to examine whether chronic EBV infections are linked to magnesium deficiency.

Reference

Chaigne-Delalande B, Li F, O’Connor GM, Lukacs MJ, Jiang P, Zheng L, Shatzer A, Biancalana M, Pittaluga S, Matthews HF, Jancel TJ, Bleesing JJ, Marsh RA, Kuijpers TW, Nichols KE, Lucas CL, Nagpal S, Mehmet H, Su HC, Cohen JI, Uzel G, Lenardo MJ. Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infections through NKG2D. Science (2013)

Dr. Lenardo’s Lab

Scientists Identify the Genetic Mutation Causing "XMEN" Disease

Primary Immune Deficiency Diseases

Last Updated July 11, 2013

Last Reviewed July 11, 2013