Autoantibody to Interferon-gamma Associated with Adult-Onset Immunodeficiency in Non-HIV Individuals in Northern Thailand

Abstract

BackgroundAutoantibody to interferon-gamma (IFN-γ) has been reported to be associated with adult-onset immunodeficiency in patients from Asian countries. This study aimed to determine the prevalence of autoantibody to IFN-γ among non-HIV patients in northern Thailand who were repeatedly infected with unusual intracellular pathogens.MethodsA cross-sectional, case-control study was conducted between March 2011 and March 2012 at Chiang Mai University Hospital. 20 cases, non-HIV, aged 18–60 years, presented with at least 2 episodes of culture or histopathology proven opportunistic infections were enrolled. Controls comprised 20 HIV-infected patients and 20 healthy adults who were age- and sex-matched with cases. Enzyme-linked immunosorbent assay (ELISA) was used to detect the presence of antibody to IFN-γ.Results11 participants in each group were female. The mean ages were 48.1±6.4, 48.3±6.3, and 47.1±6.5 years among cases, HIV-infected, and healthy controls, respectively. The opportunistic infections among 20 cases included disseminated non-tuberculous mycobacterial (NTM) infection (19 patients/24 episodes), disseminated penicilliosis marneffei (12 patients/12 episodes), and non-typhoidal Salmonella bacteremia (7 patients/8 episodes). At the cutoff level of 99 percentile of controls, the prevalence of autoantibody to IFN-γ were 100%, 0%, and 0%, among cases, HIV-infected, and healthy controls, respectively (p-value <0.001). The mean concentrations of antibody to IFN-γ were 3.279±0.662 and 0.939±0.630 O.D. among cases with and without active opportunistic infection, respectively (p-value<0.001).ConclusionsIn northern Thailand, autoantibody to IFN-γ was strongly associated with adult-onset immunodeficiency. The level of antibody to IFN-γ in patients who had active opportunistic infection was relatively higher than those without active infection.

Cryptococcosis in Anti-Interferon-Gamma Autoantibody-Positive Patients: a Different Clinical Manifestation from HIV-Infected Patients

“…6-10), most had an IFN-g Ab titer of 1:10,000. In our previous study, IFN-g Ab was rare (1/48, 2z) in the healthy control (3), and this is supported by a study in Chiang Mai, Thailand, in which 20 HIV-infected patients and 20 healthy control participants tested negative for IFN-g Ab (11). Given that the 5 healthy controls in our study all tested negative for IFN-g Ab, we contend that all of the HIV-infected patients with cryptococcosis in our study were negative for IFN-g Ab.…”

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

“…However, unlike IFN‐γ, this condition is frequently associated with pathogens other than mycobacteria, such as Salmonella , Cryptococcus neoformans , Histoplasma capsulatum , Penicillium marneffei , and varicella zoster virus. Since 2004, more than 150 adult patients with neutralizing autoantibodies against IFN‐γ have been identified . Most are of Asian descent and it was recently and elegantly shown for the first time that the production of anti‐IFN‐γ autoantibodies is under tight genetic control in humans .…”

Disseminated Mycobacterium haemophilum skeletal disease in a patient with interferon‐gamma deficiency

“…Since 2004, there have been increasing reports of severe, persistent or recurrent infections from NTM associated with autoantibodies to IFN‐γ . Recent reports suggest IFN‐γ autoantibodies may be an under‐recognised association with adult‐onset immunodeficiency especially in patients of Asian ethnicity.…”