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

Abstract

Background 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. Methods and findings 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. Conclusions 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.

Diagnosis of NTM active infection in lymphadenopathy patients with anti-interferon-gamma auto-antibody using inhibitory ELISA vs. indirect ELISA

“…Thus, detection of autoantibody titer can help with both (a) diagnosis of NTM infection in patients with lymphadenopathy prior to confirming with mycobacterial culture and/or functional test of IFN-γ neutralizing autoantibody, and (b) management of therapeutic decision-making for active or inactive infection. These results confirm a report that showed NTM-infected patients who had drug-free remission had a persistently lower level of anti-IFN-γ autoantibody than those in the non-remission group 22 . The level of anti-IFN-γ auto-antibody from drug-free remission was, moreover, decreasing over time while the non-remission group did not change 22 .…”

“…These results confirm a report that showed NTM-infected patients who had drug-free remission had a persistently lower level of anti-IFN-γ autoantibody than those in the non-remission group 22 . The level of anti-IFN-γ auto-antibody from drug-free remission was, moreover, decreasing over time while the non-remission group did not change 22 .…”

“…S4). Our results confirm that the inhibition titer is useful for clinical classification of disease activity among infected patients that normally require prolonged antimicrobial therapy 11,22 , while inactive patients who can discontinue antimycobacterial treatment have a lower autoantibody titer 22 . In order to www.nature.com/scientificreports www.nature.com/scientificreports/ demonstrate how inhibition titer can be used to predict active vs. inactive NTM infection, we tested the ability to neutralize pSTAT1 upon IFN-γ stimulation of the remaining plasma samples from 5 representative samples for each group of non-infected healthy controls, inactive infection (inhibition titer <5,000), active infection (inhibition titer at 5,000), and active infection (high titer >5,000).…”

A case report of Talaromyces marneffei Oro-pharyngo-laryngitis: a rare manifestation of Talaromycosis

“…Some specific HLA classes, such as HLA-DRB1, and HLA-DQB1 commonly discovered in Asian populations were proposed to be associated with this condition [14, 15]. Clinical infections of patients with anti-IFNɣ autoantibodies are usually disseminated diseases caused by opportunistic pathogens, such as non-tuberculous mycobacteria, particularly rapidly growing mycobacteria, Salmonella non-Typhi, Cryptococcus , Histoplasma , Talaromyces , and the Varicella-Zoster virus [16, 17]. Similar to this case report, more than half of patients developed relapsed infection from a prior infected organism or recurrent infection from a new opportunistic organism despite receiving long-term antimicrobial treatment [17].…”

Clinical findings of Talaromyces marneffei infection among patients with anti-interferon-γ immunodeficiency: a prospective cohort study

“…Patients have high titers of serum anti-IFN-γ autoAbs, which can inhibit signal transducer and activator of transcription 1 (STAT1) phosphorylation and interleukin-12 production, resulting in severe dysfunction of the Th1 response [1] and increased risk of infection by multiple intracellular pathogens, including nontuberculous Mycobacterium (NTM), Talaromyces marneffei (T. marneffei), Cryptococcus neoformans, and other intracellular pathogens [1][2][3][4][5][6][7][8][9][10][11][12]. Talaromycosis is a severe deep mycosis that mainly involves organs rich in monocyte-macrophages (i.e., the lungs, liver, and lymph nodes) and can be categorized into localized and disseminated disease.…”