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

Chen, Zhaoming; Li, Zheng-Tu; Li, Shaoqiang; Guan, Weijun; Qiu, Ye; Lei, Ziying; Zhan, Yangqing; Zhou, Hua; Sheng, Lin; Wang, Xinni; Li, Zhun; Yang, Feng; Zeng, Wen; Yao, Lin; Liu, Jing; Zhang, Jianquan; Ye, Feng

doi:10.1186/s12879-021-06255-9

Cited by 13 publications

(18 citation statements)

References 37 publications

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“…The clinical characteristics reported herein were consistent with our previous findings 12 and those published previously. 10 , 11 Patients with defective T lymphocyte function due to anti-IFN-γ autoAbs tended to have severe disseminated infection and poor clinical outcomes.…”

Section: Discussionsupporting

confidence: 92%

“…The serum anti-IFN-γ autoAb titers were determined by using an enzyme-linked immunosorbent assay kit (USCN Life Science, Inc., Wuhan, China) according to the manufacturer instructions. According to our previous study, 12 based on the 99th percentile of the anti-IFN-γ autoAb titers in 40 healthy controls, the cutoff for anti-IFN-γ autoAb positivity was 594.49 ng/mL, with higher values suggestive of higher levels of anti-IFN-γ autoAbs.…”

Section: Methodsmentioning

confidence: 98%

“…6,7 A link between anti-IFN-γ autoAbs and severe T. marneffei infection in HIV-negative patients has also been revealed. [8][9][10][11][12] The clinical presentation in such cases is often atypical and might be confounded by the manifestations of other infectious diseases. Moreover, recurrent infection can lead to lingering illness and life-threatening complications.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, recurrent infection can lead to lingering illness and life-threatening complications. [10][11][12] The association between genetic factors and anti-IFN-γ autoAb-associated immunodeficiency has been documented. The HLA class II alleles DRB1*16:02-DQB1*05:02 and HLA-DRB1*15:02-DQB1*05:01 have been strongly associated with anti-IFN-γ autoAb titers in patients from Southeast Asia.…”

Section: Introductionmentioning

confidence: 99%

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Anti-Interferon-γ Autoantibodies Impair T-Lymphocyte Responses in Patients with Talaromyces marneffei Infections

Chen¹,

Yang²,

Li³

et al. 2022

IDR

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Background: Although anti-IFN-γ autoantibodies predispose patients to Talaromyces marneffei infection, whether this is mediated by T cell attenuation remains elusive. Methods: Total peripheral blood mononuclear cells (PBMCs) from healthy donors or patients with T. marneffei infection were stimulated with M1 58−66 , and immunodominant influenza H1N1 peptide, or heat-inactivated T. marneffei in the presence of serum from anti-IFN-γ autoantibody-positive patients or healthy controls. The percentages of IFN-γ + TNF + CD8 + T cells and IFN-γ + CD4 + T cells were determined by flow cytometry and cytokines released in the supernatant were detected by Cytometric Bead Array. Furthermore, PBMCs from patients with T. marneffei infection and healthy individuals were stimulated with IFN-γ and anti-CD3/CD28 beads, and the levels of STAT1 and STAT3 phosphorylation were detected by Western blot. Results: The M1-reactive CD8 + T cells that expressed IFN-γ + TNF-α + of healthy controls were clearly reduced in serum with hightiter anti-IFN-γ autoantibodies. In addition, the CD4 + T cell response, designated by the expression of IFN-γ, against T. marneffei in PBMCs of patients were significantly decreased when cultured in high-titer anti-IFN-γ autoantibody serum culture, compared to the healthy compartments. Moreover, the release of the cytokines IFN-γ, TNF-α and IL-2 was significantly decreased, while IL-10 was significantly increased. There was no significant difference in the phosphorylation levels of STAT1 and STAT3 protein between patients and healthy controls after IFN-γ or anti-CD3/CD28 beads stimulation. Conclusion: Anti-IFN-γ autoantibodies presence in the serum inhibited CD4 + Th1 and CD8 + T cell immune responses. There was no congenital dysfunction of STAT1 and STAT3 in anti-IFN-γ autoantibody-positive patients with T. marneffei infection. These results suggest that the production of anti-IFN-γ autoAbs impair T-lymphocyte responses.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Anti-Interferon-γ Autoantibodies Impair T-Lymphocyte Responses in Patients with Talaromyces marneffei Infections

Chen¹,

Yang²,

Li³

et al. 2022

IDR

Self Cite

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“…However, the patients with anti-IFN-g autoantibody are more likely to have pleural effusion and multiple organ involvement (23). Chen et al confirmed that patients who tested positive for anti-IFN-g autoantibody usually have more frequently exhibited disseminated systemic infections with severe pleural effusion, have stronger inflammatory responses, are more likely to be infected by other intracellular pathogen, and have worse disease outcomes despite aggressive antimicrobial therapy (71).…”

Section: Anti-ifn-g Autoantibodies In Aoidmentioning

confidence: 99%

Anti-Interferon Autoantibodies in Adult-Onset Immunodeficiency Syndrome and Severe COVID-19 Infection

2021

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Adult-onset immunodeficiency syndrome due to anti-interferon (IFN)-γ autoantibodies has attracted much attention in recent years. It usually occurs in previously healthy people and usually presents as chronic, recurrent, and hard-to-control infections that can be effectively treated with aggressive antibiotic therapy. Adult-onset immunodeficiency syndrome is also referred to as AIDS-like syndrome. Anti-type I IFN (IFN-I) autoantibodies have been reported to play a significant role in the pathogenesis of coronavirus disease 2019 (COVID-19) and preexisting anti-IFN-I autoantibodies are associated with an increased risk of severe COVID-19. This review summarizes the effects of anti-IFN autoantibodies on the susceptibility and severity of various infectious diseases, including SARS-CoV-2 infection. In addition, we discuss the role of anti-IFN autoantibodies in the pathogenesis of autoimmune diseases that are characterized by recurrent infections.

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Characteristics and Outcomes of Anti-interferon Gamma Antibody-Associated Adult Onset Immunodeficiency

et al. 2023

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Purpose Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome. Methods A systematic literature review of AIGA associated disease was conducted. Serum-positive cases with detailed clinical presentations, treatment protocols, and outcomes were included. The patients were categorized into controlled and uncontrolled groups based on their documented clinical outcome. Factors associated with disease outcome were analyzed with logistic regression models. Results A total of 195 AIGA patients were retrospectively analyzed, with 119(61.0%) having controlled disease and 76 (39.0%) having uncontrolled disease. The median time to diagnosis and disease course were 12 months and 28 months, respectively. A total of 358 pathogens have been reported with nontubercular mycobacterium (NTM) and Talaromyces marneffei as the most common pathogens. The recurrence rate was as high as 56.0%. The effective rates of antibiotics alone, antibiotics with rituximab, and antibiotics with cyclophosphamide were 40.5%, 73.5%, and 75%, respectively. In the multivariate logistic analysis, skin involvement, NTM infection, and recurrent infections remained significantly associated with disease control, with ORs of 3.25 (95% CI 1.187 ~ 8.909, P value = 0.022), 4.74 (95% CI 1.300 ~ 17.30, P value = 0.018), and 0.22 (95% CI 0.086 ~ 0.551, P value = 0.001), respectively. The patients with disease control had significant AIGA titer reduction. Conclusions AIGA could cause severe opportunistic infections with unsatisfactory control, particularly in patients with recurrent infections. Efforts should be made to closely monitor the disease and regulate the immune system.

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

Cited by 13 publications

References 37 publications

Anti-Interferon-γ Autoantibodies Impair T-Lymphocyte Responses in Patients with Talaromyces marneffei Infections

Anti-Interferon-γ Autoantibodies Impair T-Lymphocyte Responses in Patients with Talaromyces marneffei Infections

Anti-Interferon Autoantibodies in Adult-Onset Immunodeficiency Syndrome and Severe COVID-19 Infection

Characteristics and Outcomes of Anti-interferon Gamma Antibody-Associated Adult Onset Immunodeficiency

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