Talaromyces marneffei and Burkholderia cepacia Co-Infection in a HIV-Uninfected Patient with Anti-Interferon-γ Autoantibodies

Abstract Background Few reports of Talaromyces marneffei (TM) or cryptococcosis infections among HIV-negative patients with high-titeranti–IFN-γautoantibodies (nAIGAs) have been published. We investigated the clinical manifestations of patients with nAIGAs and TM infections. Methods HIV-negative adults (≥18 years) were enrolled if they haddisseminated TM infection (group 1; further divided into nAIGAs positive [group 1P] and negative [group 1N]); cryptococcosis(pulmonary cryptococcosis and/or cryptococcosis of the brain)(group 2); pulmonary tuberculosis (group 3); and healthy controls (group 4) with nAIGAs detected. Complete histories, physical examinations, and routine clinical laboratory tests were obtained at baseline. Results Overall, 88 participants were in the four groups (20,13,23, and 32 in groups 1 to 4, respectively). Significant differences occurred between groups with higher nAIGAs titers (P < 0.001), and higher total white-cell and absolute neutrophil counts (P < 0.001) in group1. Lungs (90.0%), lymph nodes (60.0%), skin (55.0%), and bones (50.0%) were most common sites of involvement. Significant differences in total white-cell and absolute neutrophil counts occurred between groups IP and 1N.Patients with recurrent TM infections, particularly group 1P, had higher initial nAIGA titer. Conclusions Patients with persistent infection who died tended to have positive initial nAIGA titer. It suggests that nAIGAs may play a critical role in the pathogenesis of TM infections, and may be associated with more severe, refractory infection.

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Coinfection by Talaromyces marneffei and Mycobacterium abscessus in a human immunodeficiency virus-negative patient with anti-interferon-γ autoantibody: a case report

Journal of International Medical Research ◽

10.1177/0300060520976471 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052097647

Author(s):

Weizhong Jin ◽

Jianhong Liu ◽

Kuang Chen ◽

Ling Shen ◽

Yan Zhou ◽

...

Keyword(s):

Lymph Node ◽

Opportunistic Infections ◽

High Titer ◽

Interferon Γ ◽

Mycobacterium Abscessus ◽

Intermittent Fever ◽

Cervical Lymph Nodes ◽

Talaromyces Marneffei ◽

Ifn Γ ◽

Low Incidence

Patients with anti-interferon (IFN)-γ autoantibodies have weakened immune defenses against intracellular pathogens. Because of its low incidence and non-specific symptoms, diagnosis of anti-IFN-γ autoantibody syndrome is difficult to establish during the early stages of infection. Here, we report a patient with high titers of serum anti-IFN-γ autoantibodies suffering from opportunistic infections. The patient presented with intermittent fever for 2 weeks. During his first hospitalization, he was diagnosed with Talaromyces marneffei pulmonary infection and successfully treated with antifungal therapy. However, multiple cervical lymph nodes subsequently became progressively enlarged. Mycobacterium abscessus infection was confirmed by positive cervical lymph node tissue cultures. High-titer serum anti-IFN-γ antibodies were also detected. Following anti- M. abscessus therapy, both his symptoms and lymph node lymphadenitis gradually improved. Anti-IFN-γ autoantibody syndrome should be considered in adult patients with severe opportunistic coinfections in the absence of other known risk factors.

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

10.21203/rs.3.rs-494898/v1 ◽

2021 ◽

Author(s):

Zhao-Ming Chen ◽

Zheng-Tu Li ◽

Shao-Qiang Li ◽

Wei-Jie Guan ◽

Ye Qiu ◽

...

Keyword(s):

Clinical Laboratory ◽

Southern China ◽

Severe Disease ◽

Interferon Γ ◽

Clinical Findings ◽

Infection Group ◽

Talaromyces Marneffei ◽

Protein Levels ◽

Cell Counts ◽

Ifn Γ

Abstract Background: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China.Methods: Between January 2018 and September 2020, we enrolled patients aged 18 years or older who were HIV-negative. Patients were further stratified into four main groups: patients with T. marneffei infection (group 1, n=42), including anti-IFN-γ autoantibody-positive (group 1P) and anti-IFN-γ autoantibody-negative (group 1N) patients; patients with NTM infection (group 2, n=20); patients with pulmonary cryptococcosis (group 3, n=20); and healthy controls (group 4, n=40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded.Results: High anti-IFN-γ autoantibody titers were found in both groups 1 and 2. Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. However, the anti-IFN-γ autoantibody level did not correlate with the clinical disease course. Most of these patients had poor outcomes despite standardized antimicrobial therapy.Conclusion: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.

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

BMC Infectious Diseases ◽

10.1186/s12879-021-06255-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhao-Ming Chen ◽

Zheng-Tu Li ◽

Shao-Qiang Li ◽

Wei-Jie Guan ◽

Ye Qiu ◽

...

Keyword(s):

Clinical Laboratory ◽

Southern China ◽

Severe Disease ◽

Interferon Γ ◽

Clinical Findings ◽

Negative Group ◽

Talaromyces Marneffei ◽

Protein Levels ◽

Cell Counts ◽

Ifn Γ

Abstract Background Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China. Methods Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded. Results Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy. Conclusion T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.

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