Dot enzyme‐linked immunosorbent assay strip as a screening tool for detection of autoantibody to interferon gamma in sera of suspected cases of adult‐onset immunodeficiency

Rattanathammethee, Kritsadee; Chawansuntati, Kriangkrai; Chaiwarith, Romanee; Praparattanapan, Jutarat; Supparatpinyo, Khuanchai; Wipasa, Jiraprapa

doi:10.1002/jcla.22460

Cited by 8 publications

(6 citation statements)

References 12 publications

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“…Patients with adult-onset immunodeficiency have been identified by characterizing defects in IFN- γ signaling, which generally involve the generation of anti-IFN- γ autoAbs and are partly due to inherited mutations in IFN- γ -signaling-associated factors [3, 4]. While the detection methodology has been demonstrated and modified [3, 22, 23], a functional neutralizing assay is lacking, although an assessment of IFN- γ -activated STAT1 is usually carried out. Our study found blockade effects of anti-IFN- γ autoAbs not only on the IFN- γ signaling pathway [14] but also on IFN- γ -driven antimicrobial activity, including M1 macrophage differentiation, antimicrobial factor production, and phagocytic activation.…”

Section: Discussionmentioning

confidence: 99%

Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity

Krisnawati

Liu

Lee

et al. 2019

Journal of Immunology Research

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The interferon- (IFN-) γ expression is elicited in response to microbial infections and activates immune surveillance by antimicrobial immune elements to induce microbial killing. Patients with adult-onset immunodeficiency who suffer from recurrent infections with microbes, particularly nontuberculous mycobacteria (NTM), commonly display genetic defects in IFN-γ signaling as well as the generation of anti-IFN-γ autoantibodies (autoAbs). Because IFN-γ is an activator of macrophage differentiation and a proinflammatory activator of innate immunity, the blockade effects of the autoAbs present in NTM patient serum on IFN-γ are hypothesized to regulate the antimicrobial function of macrophages. In the presence of patient serum, IFN-γ-induced type 1 macrophage (M1) differentiation was inhibited in PMA-stimulated human monocytic THP-1 cells. Treatment with patient serum significantly blocked the production of proinflammatory factors, including cytokines/chemokines and reactive oxygen/nitrogen species, by M1 macrophages. Importantly, IFN-γ-facilitated phagocytosis and degradation of heat-killed mycobacterium were decreased by cotreatment with patient serum. These results show the blockade activity of anti-IFN-γ autoAbs on IFN-γ-mediated antimicrobial immunity in macrophages.

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Section: Discussionmentioning

confidence: 99%

Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity

Krisnawati

Liu

Lee

et al. 2019

Journal of Immunology Research

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“…However in addition, we would propose to take further advantage of the widely available Quantiferon assay: Addition of IFN gamma to the tuberculosis tube, if necessary in the presence or absence of a suitable costimulus such as lipopolysaccharide, should theoretically induce the production of TNF-α and IL12, which would be suppressed in the presence of nAIGA. Rattanathammethee et al [55 ▪ ] propose a simple easy to perform dot-ELISA assay which, although based on qualitative visual evaluation, shows excellent positive and negative predictive values. This test should be economical and could be performed even in remote places with limited testing capabilities.…”

Section: Detection and Functional Evaluation Of Anticytokine Autoantimentioning

confidence: 99%

Anticytokine autoantibodies leading to infection: early recognition, diagnosis and treatment options

Barcenas-Morales

Cortes-Acevedo

Döffinger

2019

Current Opinion in Infectious Diseases

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Purpose of review The current review gives a concise and updated overview of the relative new field of anticytokine autoantibodies (ACAA) and associated infections with a focus on recent findings regarding clinical manifestions, diagnostic and treatments. Recent findings Several recent case reports of unusual presentations of patients with neutralizing autoantibodies to IFN-γ and granulocyt macrophage colony-stimulating factor and expand the spectrum of clinical manifestations and suggest that anticytokine-mediated acquired immunodeficiency causing susceptibility to infection may be underdiagnosed. There is an expanding geographical distribution of antigranulocyt macrophage colony-stimulating factor associated Cryptococcus gattii infection. The spectrum of identified infections in patients with neutralizing antibodies to IFN-γ has a strong endemic component. Rituximab or cyclophophamide in addition to antimycobacterials could be a treatment options in refractory cases. NF-κB2 deficiency may be associated with a complex pattern of high titre neutralizing ACAA similar to autoimmune polyglandular syndrome type I and Thymoma. New technique for the detection of anticytokine antibodies are presented. Quantiferon testing, which is widely available for TB-diagnostic, may be repurposed to detect anti-IFN-γ autoantibodies. We propose that this test could be as well used to show if they are neutralizing. Summary ACAA are an emerging cause of acquired immunodeficiency which is likely underdiagnosed. Recent case reports document expanding spectra of clinical manifestations. NF-κB2 deficiency may be associated with a complex anti cytokine autoantibody pattern.

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“…Based on studies in Thailand and Taiwan, high-titers of anti-IFN-γ autoAb 7 are present in 81% of patients with NTM (52 patients) and 96% of patients with other opportunistic infections with or without NTM (45 patients); neutralizing activity of these autoAbs was suggested as a parameter for monitoring of disease onset and progression. Until now, detection of anti-IFN-γ autoAbs is developed 7,14 but is not widely used in clinical studies. This study aimed to measure anti-IFN-γ autoAbs in patients with NTM infection.…”

Section: Introductionmentioning

confidence: 99%

Functional neutralization of anti-IFN-γ autoantibody in patients with nontuberculous mycobacteria infection

Krisnawati

Liu

Lee

et al. 2019

Sci Rep

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Interferon (IFN)-γ is crucial for normal immune surveillance and exhibits immunomodulatory, antimicrobial, and anticancer activity. Patients with nontuberculous mycobacteria (NTM) infection commonly express high levels of anti-IFN-γ autoantibodies (autoAbs) and suffer from recurrent infections due to adult-onset immunodeficiency with defects in IFN-γ immune surveillance. In this study, we developed the methods for determination of anti-IFN-γ autoAbs and then characterized their neutralizing activity in patients with NTM infection. A modified sandwich ELISA-based colorimetric assay followed by immunoblot analysis detected the presence of autoAbs in three out of five serum samples. Serum levels of IFN-γ were decreased. Synthetic peptide binding assay showed variable patterns of epitope recognition in patients positive for anti-IFN-γ autoAbs. Functional tests confirmed that patient serum blocked IFN-γ-activated STAT1 activation and IRF1 transactivation. Furthermore, IFN-γ-regulated inflammation, chemokine production and cytokine production were also blocked. These results provide potentially useful methods to assay anti-IFN-γ autoAbs and to characterize the effects of neutralizing autoAbs on IFN-γ signaling and bioactivity.

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Dot enzyme‐linked immunosorbent assay strip as a screening tool for detection of autoantibody to interferon gamma in sera of suspected cases of adult‐onset immunodeficiency

Abstract: This simple method provides prompt qualitative results that can be read visually and used in facilities with limited testing capabilities.

Cited by 8 publications

References 12 publications

Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity

Blockade Effects of Anti-Interferon- (IFN-) γ Autoantibodies on IFN-γ-Regulated Antimicrobial Immunity

Anticytokine autoantibodies leading to infection: early recognition, diagnosis and treatment options

Functional neutralization of anti-IFN-γ autoantibody in patients with nontuberculous mycobacteria infection

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