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Other Infections

Immune Deficiency Cases in Asia May Be Due to Interferon-gamma Antibodies

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Antibodies against interferon-gamma, a cytokine that plays an important role in immune defense against bacteria and viruses, were detected in nearly 90% of people in Taiwan and Thailand who developed multiple opportunistic infections (OIs), researchers reported in the August 23, 2012, New England Journal of Medicine.

In recent years clinicians have reported more than 100 cases of unexplained adult-onset immunodeficiency similar to that seen in people AIDS, mostly in Asia but also a few in the U.S. These HIV negative patients have come down with OIs including non-tuberculosis mycobacterial infections, which are rare in people with normal immune function.

Now, researchers have found a possible cause of the mysterious condition: naturally occurring antibodies that attack a disease-fighting cytokine, or chemical messenger, produced by lymphocytes in response to pathogens.

Sarah Browne from the National Institute of Allergy and Infectious Diseases(NIAID) and colleagues enrolled 203 people from Taiwan and Thailand, classified into 5 groups: 52 patients with disseminated non-tuberculosis mycobacterial infections, 45 with other OIs with or without non-tuberculosis mycobacteria, 9 with disseminated (spread beyond the lungs) tuberculosis (TB), 49 with pulmonary (lungs only) TB, and 48 healthy control subjects.

Patients in the first 2 groups did not have HIV and they had CD4 T-cell counts similar to those of people in the pulmonary TB and healthy groups. Cells obtained from people with non-tuberculosis mycobacterial infections showed normal cytokine production and response to cytokine stimulation.

However, plasma from these patients inhibited interferon-gamma activity in normal cells. The researchers detected high levels of anti-interferon-gamma auto-antibodies in 81% of patients with only non-tuberculosis mycobacterial infections, 96% of patients with other OIs, and 11% of patients with disseminated TB, but in just 2% of patients with pulmonary TB and healthy controls.

The researchers also looked at 40 other antibodies directed against other cytokines. One patient with cryptococcal meningitis had auto-antibodies only against granulocyte-macrophage colony-stimulating factor, a cytokine that promotes production of certain types of white blood cells. No other anti-cytokine antibodies were associated with presence of infections. Furthermore, they found no genetic defects and no familial clustering among people with unusual infections.

"More work is needed to determine why people in Southeast Asia appear to be predisposed to the development of this autoimmune condition," according to a NIAID press release. "Because the average age of the study participants with [non-tuberculosis mycobacterial infections] or other opportunistic infections was 50 years, the investigators speculate that these antibodies develop over time as a result of combined genetic and environmental factors. Having identified the likely cause of this syndrome, the study authors say it may be possible to treat the underlying problem by targeting the cells that make the interferon-gamma autoantibodies."

8/24/12

Reference

SK Browne, PD Burbelo, P Chetchotisakd, et al. Adult-Onset Immunodeficiency in Thailand and Taiwan. New England Journal of Medicine 367(8):725-734. August 23, 2012.

Other Source

National Institute of Allergy and Infectious Diseases. NIH Researchers Find Possible Cause of Immune Deficiency Cases in Asia. NIH News press release. August 22, 2012.