Dataset Information

Intravenous Cyclophosphamide Therapy for Anti-IFN-γ Autoantibody-Associated Talaromyces marneffei Infection.

ABSTRACT: High titers of anti-interferon-γ autoantibodies (AIGAs) are an important factor leading to persistent, relapsed, and refractory infections in HIV-negative hosts infected with Talaromyces marneffei (TM). We report 5 patients treated with pulses of high-dose intravenous cyclophosphamide (IVCY) who were followed for 2 years. Before IVCY therapy, all patients had multiple relapses, with a median (interquartile range [IQR]) of 2 (1-3) instances of relapse. The median serum AIGA titers (IQR) were 58 753 (41 203-89 605) ng/mL at diagnosis, 48 189.4 (15 537-83 375) ng/mL before IVCY therapy, and 10 721.2 (5637-13 245) ng/mL at the end of IVCY therapy (P < .05). After 3 months of follow-up, the median AIGA titers (IQR) rose gradually to 21 232.6 (9896-45 626) ng/mL, and to 37 464.2 (19 872-58 321) ng/mL at 24 months (P < .05). Five patients discontinued antimicrobial therapy within 3-12 months after completion of IVCY therapy, but only 1 patient had a relapse. In conclusion, pulses of short-term and high-dose IVCY can effectively reduce AIGA titers.

SUBMITTER: Zeng W

PROVIDER: S-EPMC9745774 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Intravenous Cyclophosphamide Therapy for Anti-IFN-γ Autoantibody-Associated <i>Talaromyces marneffei</i> Infection.

Zeng Wen W Tang Mengxin M Yang Meiling M Fang Gaoneng G Tang Shudan S Zhang Jianquan J

Open forum infectious diseases 20221111 12

High titers of anti-interferon-γ autoantibodies (AIGAs) are an important factor leading to persistent, relapsed, and refractory infections in HIV-negative hosts infected with <i>Talaromyces marneffei</i> (TM). We report 5 patients treated with pulses of high-dose intravenous cyclophosphamide (IVCY) who were followed for 2 years. Before IVCY therapy, all patients had multiple relapses, with a median (interquartile range [IQR]) of 2 (1-3) instances of relapse. The median serum AIGA titers (IQR) we ...[more]

PMID: 36519123

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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:BackgroundTalaromyces marneffei (T marneffei), known as a significant pathogen in patients with AIDS in Southeast Asia, is a dimorphic fungus, which can cause deadly systematic infection in immunocompromised hosts. What is more, the dimorphic phase transition has been reported as a conspicuous process linked with virulence. Interestingly, the yeast form was found in infected individuals, representing the pathogenic phase. However, few researches were found to study the mechanism of dimorphic transition. Thus, a diverse insight into the dimorphic switch mechanism, is urgently needed and we are the first one to research the mechanism of dimorphism.MethodsFirstly, we investigated the microarray of T. marneffei in the Gene Expression Omnibus database (GEO) for differentially expressed genes (DEGs). Then Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 was employed to analyze the underlying enrichment and pathway in biological process of DEGs. Meanwhile, protein-protein interaction (PPI) network was constructed using STRING database. On the strength of the theory that similar amino acid sequences share similar structures, which play a decisive role on the function of protein, three dimensional structures of hub-genes were predicted to further investigate the likely function of hub-genes.ResultsGSE51109 was elected as the eligible series for the purpose of our research, including GSM1238923 (GSM23), GSM1238924 (GSM24), and GSM1238925 (GSM25). PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were the most remarkable genes in all of the three PPI networks, thus, were viewed as hub-genes. With regard to the three-dimensional construction, except that there was no significant prediction structure of PMAA_092900 with the criterion seq identify > 30%, GMQE: 0-1, QMEAN4: -4-0, the parallel templates for four structures were Crystal structure of Saccharomyces cerevesiae mitochondrial NADP(+)-dependent isocitrate dehydrogenase in complex with isocitrate, Organellar two-pore channels (TPCs), Yeast Isocitrate Dehydrogenase (Apo Form) and Crystal Structure Of ATP-Dependent Phosphoenolpyruvate Carboxykinase From Thermus thermophilus HB8 in order.ConclusionThe dimorphic transition of T. marneffei was viewed as a pathogenic factor and DEGs were observed. In-depth study of the function and pathway of DEGs revealed that PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were most likely acting as the hub-genes and were likely taking effect through regulating energy metabolism.

Dataset Information

Intravenous Cyclophosphamide Therapy for Anti-IFN-γ Autoantibody-Associated Talaromyces marneffei Infection.

Publications

Intravenous Cyclophosphamide Therapy for Anti-IFN-γ Autoantibody-Associated <i>Talaromyces marneffei</i> Infection.

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