Research Article: Clinical outcome and laboratory markers for predicting disease activity in patients with disseminated opportunistic infections associated with anti-interferon-γ autoantibodies

Date Published: April 25, 2019

Publisher: Public Library of Science

Author(s): Nasikarn Angkasekwinai, Yupin Suputtamongkol, Pakpoom Phoompoung, Manop Pithukpakorn, Ekkarat Wongswat, Pinklow Umrod, Sasima Tongsai, Suporn Foongladda, Pradeep Kumar.


Clinical courses and treatment outcomes are largely unknown in patients with adult-onset immunodeficiency associated with anti-interferon-gamma autoantibodies due to the fact that it was recently recognized and anti-IFN-γ auto-Abs detection is not widely available.

Non-HIV-infected adult patients with detectable anti-IFN-γ auto-Abs diagnosed and followed at Siriraj Hospital, Bangkok, Thailand during January 2013 to November 2016 were prospectively studied. At each follow-up visit, patients were classified as stable or active disease according to symptoms and signs, and all proven OIs were recorded. Laboratory parameters, including erythrocyte sedimentation rate, C-reactive protein, and anti-IFN-γ auto-Abs level, were compared between active and stable disease episodes. We identified 80 patients with this clinical syndrome and followed them up during study period. Seventy-nine patients developed overall 194 proven opportunistic infections. Mycobacterium abscessus (34.5%) and Salmonella spp. (23.2%) were the two most common pathogens identified among these patients. Sixty-three patients were followed for a median of 2.7 years (range 0.6–4.8 years). Eleven (17.5%) patients achieved the drug-free remission period for at least 9 months. Four patients died. Anti-IFN-γ auto-Abs concentration was significantly lower at baseline and decreased over time in the drug-free remission group compared to another group (p = 0.001). C-reactive protein, erythrocyte sedimentation rate and white cell count were found to be useful biomarkers for determining disease activity during follow-up.

Reinfection or relapse of OIs is common despite long-term antimicrobial treatment in patients with anti-IFN-γ auto-Abs. Treatment to modify anti-IFN-γ auto-Abs production may improve long-term outcomes in this patient population.

Partial Text

Adult-onset immunodeficiency due to anti-interferon-gamma autoantibodies (anti-IFN-γ auto-Abs) is a distinct clinical syndrome of disseminated nontuberculous mycobacteria (NTM) or other opportunistic (OI) infections in previously healthy adult patients in association with anti-IFN- γ auto-Abs [1]. Since first described in 2004, this syndrome has emerged as a very difficult-to-treat infectious disease in otherwise immunocompetent adults from Asian countries, including Thailand [2–9]. The dysfunction of IFN-γ by naturally occurring neutralizing antibodies against IFN-γ causes disrupted downstream response ability and impaired killing ability capacity intracellular organisms by macrophages[10]. Additional abnormal immune responses in adult-onset immunodeficiency characterized by reduced production of interleukin (IL)-2 and tumor necrosis factor (TNF)-α may be a consequence of T cell exhaustion following chronic antigenic stimulation [11]. As a result, patients with anti-IFN-γ auto-Abs typically present with disseminated infection caused by opportunistic intracellular pathogens, especially NTM [1, 12–14]. A significant proportion of patients are co-infected or present with other intracellular pathogens, including nontyphoidal Salmonella spp., Cryptococcus neoformans, Talaromyces marneffei, and Varicella zoster virus (VZV) [1, 12].

Herein, we described the clinical presentation, clinical course and treatment outcome of 80 patients with detectable anti-IFN-γ auto-Abs diagnosed in a single hospital in Thailand. In all except one patient, initial clinical presentations were associated with disseminated OIs. Although the clinical presentation of that patient was very similar to that of the other patients, his condition deteriorated despite all available antimicrobial, including antimycobacterial therapies. His dramatic clinical improvement after plasma exchange therapy raises the possibility that immunoglobulin might have played a role in his autoimmunity or immunodeficiency. Unfortunately, we had no additional information regarding this patient after his discharge.




Leave a Reply

Your email address will not be published.