M. fortuitum a “rapidly-growing” Mycobacterium Credit CDC PHIL
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Investigators at the NIH have identified an antibody suspected to be the cause of a noninfectious AIDS-like syndrome observed in Asia in recent years, one that can make people susceptible to opportunistic infections like those from nontuberculous mycobacteria (NTM).
Mycobacteria are slender, rod-shaped bacteria commonly found in the environment throughout the world.
Generally divided into three groups, the most famous are the bacilli that cause cause Tuberculosis and Leprosy (Hansen’s Disease) – while the third group - responsible for NTMs - are less well known.
Nontuberculous mycobacterial (NTMs) infections are rarely seen among non-HIV positive (or otherwise pulmonary or immune compromised) patients, but has been observed with increasing frequency over the past decade, particularly in Asia.
A couple of cites from the last decade include:
J Infect. 2006;53:77–84
Lai CC, Lee LN, Ding LW, Yu CJ, Hsueh PR, Yang PC.
Clin Infect Dis. 2007 Aug 15;45(4):421-7. Epub 2007 Jul 5.
Chetchotisakd P, Kiertiburanakul S, Mootsikapun P, Assanasen S, Chaiwarith R, Anunnatsiri S
While some sort of immune compromising condition has been associated with these opportunistic infections, until now the mechanism behind them has been a mystery.
Today, an NIH study appearing in the NEJM finds that high-titers of anti–interferon-γ autoantibodies (i.e. an antibody directed against the body’s own immune system) are associated with opportunistic infections -like NTM - in non-HIV positive patients.
Interferon-y (IFN-γ) – or type II interferon - is a cytokine that is a critical component of our body’s innate and adaptive immune system. Antibodies that inhibit or neutralize their function would be expected to greatly assist opportunistic infections in spreading.
First a link to the study, then more details from the NIH press release.
Adult-Onset Immunodeficiency in Thailand and Taiwan
Sarah K. Browne, M.D., Peter D. Burbelo, Ph.D., Ploenchan Chetchotisakd, M.D., Yupin Suputtamongkol, M.D., Sasisopin Kiertiburanakul, M.D., Pamela A. Shaw, Ph.D., Jennifer L. Kirk, B.A., Kamonwan Jutivorakool, M.D., Rifat Zaman, B.S., Li Ding, M.D., Amy P. Hsu, B.A., Smita Y. Patel, M.D., Kenneth N. Olivier, M.D., Viraphong Lulitanond, Ph.D., Piroon Mootsikapun, M.D., Siriluck Anunnatsiri, M.D., Nasikarn Angkasekwinai, M.D., Boonmee Sathapatayavongs, M.D., Po-Ren Hsueh, M.D., Chi-Chang Shieh, M.D., Ph.D., Margaret R. Brown, B.S., Wanna Thongnoppakhun, Ph.D., Reginald Claypool, R.N., Elizabeth P. Sampaio, M.D., Ph.D., Charin Thepthai, M.Sc., Duangdao Waywa, M.Sc., Camilla Dacombe, R.N., Yona Reizes, R.N., Adrian M. Zelazny, Ph.D., Paul Saleeb, M.D., Lindsey B. Rosen, B.S., Allen Mo, B.S., Michael Iadarola, Ph.D., and Steven M. Holland, M.D.
N Engl J Med 2012; 367:725-734 August 23, 2012
Conclusions
Neutralizing anti–interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection.
And more details from NIH/NIAID.
NIH Researchers Find Possible Cause Of Immune Deficiency Cases In Asia
Autoantibody May Cause Susceptibility to Opportunistic Infections
WHAT:
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.
ARTICLE:
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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