Researchers have discovered an adult-onset immunodeficiency syndrome with symptoms similar to those of advanced HIV in Thailand and Taiwan.
Sarah Browne (National Institutes of Health, Bethesda, Maryland, USA) and colleagues enrolled 155 patients, aged 18 to 78 years, with suspected immunodeficiency and 48 healthy controls (group 5) for comparison purposes.
Fifty-two patients had nontuberculous mycobacterial (NTM) infection (group 1), 45 had another opportunistic infection with or without NTM infection (group 2) - both infections that commonly affect immunocompromised patients such as those with HIV - nine had disseminated tuberculosis (group 3), and 49 had pulmonary tuberculosis (group 4).
The patients with NTM and/or opportunistic infection had similar CD4+ T-lymphocyte counts to those with disseminated or pulmonary tuberculosis despite being negative for HIV infection.
Patients in groups 1 and 2 also had unusually high levels of autoantibodies against interferon-γ, at 81% and 96%, respectively, compared with 11%, 2%, and 2% of those in groups 3, 4, and 5, respectively.
Notably, no other anticytokine autoantibodies or genetic mutations were associated with the infections seen in groups 1 and 2.
Interferon-γ helps the immune system to clear infections, therefore the presence of interferon-γ autoantibodies makes the affected individuals very vulnerable to opportunistic infections.
"Our study showed that this adult onset immunodeficiency syndrome is strongly associated with high-titer neutralizing antibodies to interferon-γ, supporting the central role of interferon-γ in the control of numerous pathogens," write Browne and team in The New England Journal of Medicine.
"Since many patients with anti-interferon-γ autoantibodies remain actively infected despite antimicrobial therapy, this observation suggests that therapeutic targeting of anti interferon-γ autoantibodies may warrant investigation," they conclude.
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