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Severe Paradoxical Reaction During Treatment of Disseminated Tuberculosis in a Patient With Neutralizing Anti-IFNγ Autoantibodies.

ABSTRACT: Interferon-gamma (IFNγ) neutralizing autoantibodies are associated with disseminated nontuberculous mycobacterial infections. We report a previously healthy Thai woman with disseminated tuberculosis and high-titer IFNγ-neutralizing autoantibodies, who developed a severe inflammatory reaction during anti-tuberculosis treatment. IFNγ contributes to host control of tuberculosis but appears inessential for tuberculosis paradoxical reactions.

SUBMITTER: Xie YL

PROVIDER: S-EPMC4772847 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Severe Paradoxical Reaction During Treatment of Disseminated Tuberculosis in a Patient With Neutralizing Anti-IFNγ Autoantibodies.

Xie Yingda L YL Rosen Lindsey B LB Sereti Irini I Barber Daniel L DL Chen Ray Y RY Hsu Denise C DC Qasba S Sonia SS Zerbe Christa S CS Holland Steven M SM Browne Sarah K SK

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20151208 6

Interferon-gamma (IFNγ) neutralizing autoantibodies are associated with disseminated nontuberculous mycobacterial infections. We report a previously healthy Thai woman with disseminated tuberculosis and high-titer IFNγ-neutralizing autoantibodies, who developed a severe inflammatory reaction during anti-tuberculosis treatment. IFNγ contributes to host control of tuberculosis but appears inessential for tuberculosis paradoxical reactions. ...[more]

PMID: 26646678

Similar Datasets

Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis.

Project description:BackgroundCryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF.MethodsWe reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis.ResultsPeripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients.ConclusionsWe report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.

| S-EPMC9947894 | biostudies-literature

Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-? autoantibodies and disseminated nontuberculous mycobacterial infections.

Project description:Neutralizing anti-interferon-? autoantibody (nAIGA)-associated immunodeficiency is an emerging medical issue worldwide. In the present study, we describe and discuss the clinical features and outcomes of patients with nAIGAs and disseminated infections by nontuberculous mycobacteria (dNTM).We thoroughly reviewed the medical records of all patients. Microorganisms and nAIGAs were identified using previously described methods with modifications. All data were calculated and analyzed using SPSS software.Among 46 adult patients with dNTM infections, we identified 45 cases (97.8%) with nAIGAs. The average patient age was 58.6 years, and there was no sex predominance. Cervical lymphadenitis (81.8%) was the most common clinical manifestation. Endocrine disorder was the leading comorbidity (7 cases). Malignancies were found in 4 patients, and all of the malignancies originated from the T-cell/macrophage lineage. More than half of the identifiable isolates were slow-growing NTMs. Twenty-eight (62.2%) and 18 (40.0%) patients had a history of zoster and salmonellosis, respectively. A high proportion of patients with recurrent episodes of NTM infection or a history of zoster and dNTM infection had initial nAIGA titers ?10 dilution (P?<?0.05). Twenty-seven patients (60.0%) required long-term antimycobacterial therapy and had at least 1 episode of recurrent NTM disease. No mortality was related to dNTM infection.In Taiwan, nAIGAs are a recently recognized mechanism of dNTM infection. Long term of antibiotic treatment and adherence to medical advice are necessary to improve the clinical outcome of patients with nAIGAs.

| S-EPMC4998320 | biostudies-literature

Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections.

Project description:Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression. Here we investigated the involvement of anti-IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti-IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti-IFN-γ autoantibodies was strongly associated with HLA-DRB1*16:02 and -DQB1*05:02 alleles in these patients. We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti-IFN-γ autoantibody-associated HLA class II DRB1*16:02 and DQB1*05:02 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.

| S-EPMC7953730 | biostudies-literature

Infliximab for Intractable Paradoxical Reaction in Culture-Negative Tuberculosis Meningitis.

Project description: Not available

| S-EPMC10921041 | biostudies-literature

Neutralizing Type I Interferon Autoantibodies in Japanese Patients With Severe COVID-19.

Project description:Purpose Autoantibodies (aAbs) to type I interferons (IFNs) have been found in <1% of individuals under the age of 60 in the general population, with the prevalence increasing among those over 65. Neutralizing autoantibodies (naAbs) to type I IFNs have been found in at least 15% of patients with life-threatening COVID-19 pneumonia in several cohorts of primarily European descent. We aimed to define the prevalence of aAbs to IFN-α2 in 3,456 Japanese controls aged 20-91 and of aAbs and naAbs to IFN-α2 and IFN-ω in 627 Japanese COVID-19 patients aged 0-104, among whom were 170 critical, 235 severe, 112 moderate, 105 mild, and 5 asymptomatic infections. Methods ELISA and ISRE reporter assays were used to detect aAbs and naAbs using E. coli-produced IFNs. Results In an uninfected general Japanese population aged 20-91, we found aAbs in 0.087% of individuals. naAbs to type I IFNs (IFN-α2 and/or IFN-ω, 100 pg/mL) were detected in 10.6% of patients with critical infections, 2.6% of patients with severe infections, and ≤1% of patients with asymptomatic to mild infections. They were higher in COVID-19 patients over 50 (5.8%) than in younger patients (0%) and higher in men (5.5%) than in women (1.1%). A significant but not strong correlation between aAbs and naAbs to IFN-α2 existed (r=-0.307, p-value<0.0001), stressing the importance of measuring naAbs. Conclusion In the largest study focusing on a single ethnic and geographic group, we show that Japanese individuals with pre-existing naAbs have a much higher risk of life-threatening COVID-19 pneumonia.

| S-EPMC8923117 | biostudies-literature

Neutralizing Type I Interferon Autoantibodies in Japanese Patients with Severe COVID-19.

Project description:PurposeAutoantibodies (aAbs) to type I interferons (IFNs) have been found in less than 1% of individuals under the age of 60 in the general population, with the prevalence increasing among those over 65. Neutralizing autoantibodies (naAbs) to type I IFNs have been found in at least 15% of patients with life-threatening COVID-19 pneumonia in several cohorts of primarily European descent. We aimed to evaluate the prevalence of aAbs and naAbs to IFN-α2 or IFN-ω in Japanese patients who suffered from COVID-19 as well as in the general population.MethodsPatients who suffered from COVID-19 (n = 622, aged 0-104) and an uninfected healthy control population (n = 3,456, aged 20-91) were enrolled in this study. The severities of the COVID-19 patients were as follows: critical (n = 170), severe (n = 235), moderate (n = 112), and mild (n = 105). ELISA and ISRE reporter assays were used to detect aAbs and naAbs to IFN-α2 and IFN-ω using E. coli-produced IFNs.ResultsIn an uninfected general Japanese population aged 20-91, aAbs to IFNs were detected in 0.087% of individuals. By contrast, naAbs to type I IFNs (IFN-α2 and/or IFN-ω, 100 pg/mL) were detected in 10.6% of patients with critical infections, 2.6% of patients with severe infections, and 1% of patients with mild infections. The presence of naAbs to IFNs was significantly associated with critical disease (P = 0.0012), age over 50 (P = 0.0002), and male sex (P = 0.137). A significant but not strong correlation between aAbs and naAbs to IFN-α2 existed (r = - 0.307, p value < 0.0001) reinforced the importance of measuring naAbs in COVID-19 patients, including those of Japanese ancestry.ConclusionIn this study, we revealed that patients with pre-existing naAbs have a much higher risk of life-threatening COVID-19 pneumonia in Japanese population.

| S-EPMC9243824 | biostudies-literature

Paradoxical Reaction in a Patient with Hidradenitis Suppurativa Undergoing Adalimumab Treatment.

Project description: Not available

| S-EPMC9380276 | biostudies-literature

Neutralizing Anti-interferon-γ Autoantibodies: an Ameliorating Factor in COVID-19 Infection?

Project description: Not available

| S-EPMC8311417 | biostudies-literature

Vaccination prevents severe COVID-19 outcome in patients with neutralizing type 1 interferon autoantibodies.

Project description:A hallmark of patients with autoimmune polyendocrine syndrome type 1 (APS-1) is serological neutralizing autoantibodies against type 1 interferons (IFN-I). The presence of these antibodies has been associated with severe course of COVID-19. The aims of this study were to investigate SARS-CoV-2 vaccine tolerability and immune responses in a large cohort of patients with APS-1 (N = 33) and how these vaccinated patients coped with subsequent infections. We report that adult patients with APS-1 were able to mount adequate SARS-CoV-2 spike-specific antibody responses after vaccination and observed no signs of decreased tolerability. Compared with age- and gender-matched healthy controls, patients with APS-1 had considerably lower peak antibody responses resembling elderly persons, but antibody decline was more rapid in the elderly. We demonstrate that vaccination protected patients with APS-1 from severe illness when infected with SARS-CoV-2 virus, overriding the systemic danger of IFN-I autoantibodies observed in previous studies.

| S-EPMC10251722 | biostudies-literature

Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients.

Project description:Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5-15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5-97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.

| S-EPMC11448868 | biostudies-literature

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