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New Immune-Deficiency Illness Emerging in East Asia

By Barbara Bronson Gray
HealthDay Reporter

WEDNESDAY, Aug. 22 (HealthDay News) -- Investigators say they've identified an emerging immune-deficiency syndrome that is killing or sickening people in East Asia.

Although human immunodeficiency virus (HIV) is not linked to the illness, the illnesses appear similar to what people with HIV often get, say the team from the U.S. National Institutes of Health.

The new syndrome, which does not seem to pass from person to person, involves an immune-system antibody that blocks a molecule critical to fighting off infections and auto-immune diseases.

The antibody works against a common protective molecule called interferon-gamma (IFN-gamma), triggering immunodeficiency in some adults, the research team said.

People with the syndrome seem especially susceptible to infections caused by what are called opportunistic microbes, which can lie dormant in the body for years but are activated and multiply when the body's immune system is weakened. They're more likely to get diseases such as nontuberculous mycobacteria (NTM), a rare cousin to tuberculosis that can cause severe lung disease.

NTM and other opportunistic diseases often are seen in people with immune deficiency, but are rare in those with healthy immune systems. Researchers in countries such as Taiwan and Thailand have recently reported several cases of NTM in people with no history of immune-system problems.

"It's too soon to know the cause," said Dr. Sarah Browne, lead author of the study, which was published Aug. 23 in the New England Journal of Medicine. "The problem could be related to something genetic in people of Asian descent or it could be tied to environmental factors, but it's too early to know."

Browne, who is assistant clinical investigator at the U.S. National Institute of Allergy and Infectious Disease in Bethesda, Md., said although some people with the problem become extremely ill and may die, others experience a long-term, chronic disease that waxes and wanes. And although some are susceptible to infectious illnesses, others develop auto-immune diseases such as rheumatoid arthritis or lupus.

"This is a big, big finding," said Dr. Marc Siegel, associate professor of medicine at New York University Langone Medical Center in New York City.

"There's a sub-group of Asians that probably have a genetic abnormality that's making them susceptible to an auto-immune problem making antibodies to interferon," he explained. "This reemphasizes how important interferon is [to the immune system]. Basically, it stabilizes cells so viruses can't transmit from cell to cell, which obviously cuts down on viral infections."

Siegel boils it down to this: "When interferon is in trouble -- basically in this case because there are antibodies working against it -- opportunistic infections can spread."

Siegel explained how the threat posed by the IFN-gamma antibodies is different from that seen with HIV.

"In this case, the body is making antibodies against itself, and in HIV it's an actual viral infection," he said.

The study involved 203 participants from Thailand and Taiwan between the ages of 18 and 78; 52 had NTM infections, 45 had other opportunistic infections (some also with NTM co-infection), 58 had tuberculosis and 48 were healthy. All were HIV-negative. The researchers checked blood samples for antibodies and found 88 percent of the people with NTM or other opportunistic infections had antibodies that blocked their IFN-gamma.

The researchers noted that people with NTM or other opportunistic infections tended to be 50 years of age or older, suggesting that the syndrome might develop over time.

Browne pointed out that more patients with the antibody blockers may fall under the radar of local health officials because they respond positively to antibiotics and get better. "We're only seeing the ones who don't respond to antibiotics," she noted.

The challenge, Browne said, is to get a handle on what's causing the disease.

"We need to understand why and how people make these antibodies, be able to predict who will get better and who will get sicker, and find treatments that target the antibodies directly," she said.

Browne believes there could be a silver lining to the emergence of the new illness, because it could point to new avenues for treating infectious disease. "There may be diseases we're treating now with antibiotics that may benefit more from manipulating the immune system," she theorized.

More information

To learn more about NTM, visit the American Lung Association.

SOURCES: Sarah Browne, M.D., assistant clinical investigator, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Md.; Marc Siegel, M.D., associate professor of medicine, New York University Langone Medical Center, New York City; New England Journal of Medicine, online edition, Aug. 22, 2012

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