Dataset Information

Talaromyces marneffei and Mycobacterium tuberculosis co-infection in a patient with high titer anti-interferon-γ autoantibodies: a case report.

ABSTRACT:

Background

High-titer anti-interferon (IFN)-γ autoantibodies are strongly associated with intracellular pathogens such as nontuberculous mycobacteria and Talaromyces marneffei, but they are not as commonly associated with Talaromyces marneffei co-infected with Mycobacterium tuberculosis.

Case presentation

Herein, we report a case of an HIV-negative Chinese man with a severe, disseminated co-infection of Talaromyces marneffei and Mycobacterium tuberculosis, who had a high-titer of anti IFN-γ autoantibodies and a CFI heterozygous nonsense gene mutation. The patient rapidly developed sepsis and died. Through by flow cytometry for CD4⁺ T cells' intracellular phosphorylated STAT-1 and Th1 cells (CD4⁺ IFN-γ⁺ cells), we found that the patient's serum can inhibited IFN γ-induced CD4⁺ T cells' STAT-1 phosphorylation and Th1 cell differentiation in normal peripheral blood mononuclear cells, but this phenomenon was not observed in normal control's serum. In addition, the higher serum concentration in the culture medium, the more obvious inhibition of Th1 cell differentiation.

Conclusions

For HIV-negative individuals with relapsing, refractory, fatal double or multiple intracellular pathogen infections, especially Talaromyces marneffei, clinicians should be aware that if they might be dealing with adult-onset immunodeficiency syndrome due to high-titer anti-IFN-γ autoantibodies. Systematic genetic and immunological investigations should also be performed.

SUBMITTER: Qiu Y

PROVIDER: S-EPMC8796477 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Talaromyces marneffei and Mycobacterium tuberculosis co-infection in a patient with high titer anti-interferon-γ autoantibodies: a case report.

Qiu Ye Y Pan Mianluan M Yang Zhenming Z Zeng Wen W Zhang Hui H Li Zhengtu Z Zhang Jianquan J

BMC infectious diseases 20220128 1

<h4>Background</h4>High-titer anti-interferon (IFN)-γ autoantibodies are strongly associated with intracellular pathogens such as nontuberculous mycobacteria and Talaromyces marneffei, but they are not as commonly associated with Talaromyces marneffei co-infected with Mycobacterium tuberculosis.<h4>Case presentation</h4>Herein, we report a case of an HIV-negative Chinese man with a severe, disseminated co-infection of Talaromyces marneffei and Mycobacterium tuberculosis, who had a high-titer of ...[more]

PMID: 35090402

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Project description:BackgroundAnti-interferon-γ autoantibodies syndrome (AIGAs syndrome) is characterized by disseminated infections involving various pathogens. The clinical manifestations of AIGAs syndrome with Talaromyces marneffei (TM) infection are not yet completely understood.MethodsA prospective cohort study was conducted at the First Affiliated Hospital of Guangxi Medical University from January 2021 to February 2024. Patients diagnosed with TM infection were categorized into two groups: AIGAs-positive with TM infection group (Group 1) and AIGAs-negative with TM infection group (Group 2). We analyzed the clinical manifestations, laboratory data, imaging findings, and pathological characteristics of the patients to gain insights into the disease's clinical features.ResultsA total of 80 AIGAs-positive patients with TM infection (Group 1) and 23 AIGAs-negative patients with TM infection (Group 2) were enrolled. Disseminated infection was significantly more common among Group 1 patients (P < 0.001). Patients in Group 1 had higher serum G test levels than those in Group 2 (P < 0.001). They also showed higher levels of white blood cells, neutrophils, lymphocytes, eosinophils, monocytes, C-reactive protein, erythrocyte sedimentation rate, serum ferritin, globulin, immunoglobulin (Ig)G, IgE, and IgG4 (P < 0.05). Common infection sites included the lungs, lymph nodes, bones, skin, and blood in Group 1 patients. Coinfections were frequently with cytomegalovirus (CMV) and non-tuberculous mycobacteria (NTM). Among patients with bone involvement, 92.6% had systemic involvement, while 7.14% had localized involvement. Chest CT, bronchoscopy, and pathology presentations were varied. During a mean 26-month follow-up, 63.63% of patients had exacerbations; 44.9% due to reactivation of the original pathogen and 55.1% due to new pathogen infections. The multivariable Cox regression analysis indicated that dyspnea and bloodstream infection are significant risk factors for the exacerbation of AIGAs-Positive Patients with TM Infection (P < 0.05).ConclusionsAIGAs-positive patients with TM infection showed elevated inflammatory markers, abnormal immune indices, increased serum G test levels, and disseminated infections involving multiple organs. The most common coinfections were CMV and NTM. Chest imaging, bronchoscopy, and pathological findings can present diversity.

Project description:ObjectiveNeutralizing anti-interferon (IFN)-γ autoantibodies are linked to opportunistic infections (OIs). To explore the association between anti-IFN-γ autoantibodies and OIs in patients with adult-onset Still's disease (AOSD), we aimed to examine the ability of these autoantibodies to blockade signal transducer and activator of transcription (STAT1)-phosphorylation and chemokines production.MethodsSerum titers of anti-IFN-γ autoantibodies were quantified using ELISA in 29 AOSD and 22 healthy controls (HC). The detectable autoantibodies were verified with immunoblotting assay, and their neutralizing capacity against IFN-γ-signaling was evaluated with flow-cytometry analysis and immunoblotting. IFN-γ-mediated production of supernatant chemokines, including monocyte chemoattractant protein-1 (MCP-1) and IFN-γ inducible protein-10 (IP-10), were measured by ELISA.ResultsAmong 29 AOSD patients, high titers of anti-IFN-γ neutralizing autoantibodies were detectable in two patients with OIs. Immunoblotting assay revealed more effective inhibition of STAT1-phosphorylation in THP-1 cells treated with sera from autoantibody-positive AOSD patients (56.7 ± 34.79%) compared with those from HC (104.3 ±29.51%), which was also demonstrated in flow-cytometry analysis (47.13 ± 40.99 vs. 97.92 ± 9.48%, p < 0.05). Depleted serum IgG from anti-IFN-γ autoAbs-positive AOSD patients with OIs restored phosphorylated STAT-1 upon IFN-γ treatment. Sera from autoantibody-positive AOSD patients more effectively inhibited IFN-γ-mediated production of MCP-1 (45.65 pg/ml) and IP-10 (22.44 pg/ml) than sera from HC (263.1 pg/ml and 104.0 pg/ml, both p < 0.05). Serum samples showing the strongest inhibition of IFN-γ-signaling were from two patients with high-titer autoantibodies and OIs.ConclusionAOSD patients have a high positive rate and titers of anti-IFN-γ autoantibodies. The remarkable blockade effect of high-titer autoantibodies on IFN-γ-mediated STAT1-phosphorylation and chemokines could make these patients susceptible to OIs.

Dataset Information

Talaromyces marneffei and Mycobacterium tuberculosis co-infection in a patient with high titer anti-interferon-γ autoantibodies: a case report.

Background

Case presentation

Conclusions

Publications

Talaromyces marneffei and Mycobacterium tuberculosis co-infection in a patient with high titer anti-interferon-γ autoantibodies: a case report.

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