A clinical study led by National Institutes of Health investigators has
identified an antibody that compromises the immune systems of HIV-negative
people, making them susceptible to infections with opportunistic microbes such
as nontuberculous mycobacteria (NTM).
In this study conducted at
hospitals in Thailand and Taiwan, the researchers found that the majority of
study participants with opportunistic infections made an antibody against
interferon-gamma (IFN-gamma), a cell-signaling molecule thought to play a major
role in clearing harmful infections. The study findings will appear online in
the August 23rd issue of the New England Journal of Medicine.
NTM are close relatives of the
bacterium that causes tuberculosis and can cause severe lung disease. NTM and
other opportunistic infections are common in people with immune deficiency
diseases, such as AIDS, but they are rare in people with healthy immune
systems. However, researchers in Southeast Asia have recently reported several
cases of NTM infections in people with no known problems with their immune
systems.
The study, led by Sarah Browne,
M.D., of the National Institute of Allergy and Infectious Diseases, and Peter
Burbelo, Ph.D., of the National Institute of Dental and Craniofacial Research,
enrolled 203 people, ages 18 to 78 years old. Of these participants, 52 had NTM
infections, 45 had other opportunistic infections with or without NTM
co-infection, 58 had tuberculosis, and 48 were healthy volunteers. All
participants were HIV-negative.
The investigators examined
participant blood samples for antibodies to cell-signaling molecules such as
IFN-gamma. Eighty-eight percent of the people with NTM or other opportunistic
infections had antibodies that blocked their own IFN-gamma (called
autoantibodies).
The autoantibodies inhibited
IFN-gamma function, hindering the immune system's ability to clear infection,
causing a syndrome that made these study participants more vulnerable to
opportunistic infections.
More work is needed to determine
why people in Southeast Asia appear to be predisposed to the development of
this autoimmune condition. Because the average age of the study participants
with NTM 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 IFN-gamma
autoantibodies.
More information: SK Browne et al. Adult
onset immunodeficiency in Thailand and Taiwan. New England Journal of Medicine.
DOI: 10.1056/NEJMoa1111160 (2012).
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