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  • 1
    Online Resource
    Online Resource
    Case Report: Interferon-γ Restores Monocytic Human Leukocyte Antigen Receptor (mHLA-DR) in Severe COVID-19 With Acquired Immunosuppression Syndrome
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-4-7)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-4-7)
    Abstract: The major histocompatibility complex (MHC) class II characterized by monocytes CD14+ expression of human leukocyte antigen receptors (HLA-DR), is essential for the synapse between innate and adaptive immune response in infectious disease. Its reduced expression is associated with a high risk of secondary infections in septic patients and can be safely corrected by Interferon-y (IFNy) injection. Coronavirus disease (COVID-19) induces an alteration of Interferon (IFN) genes expression potentially responsible for the observed low HLA-DR expression in circulating monocytes (mHLA-DR). Methods We report a case of one-time INFy injection (100 mcg s.c.) in a superinfected 61-year-old man with COVID-19–associated acute respiratory distress syndrome (ARDS), with monitoring of mHLA-DR expression and clinical tolerance. Observations Low mHLA-DR pretreatment expression (26.7%) was observed. IFNy therapy leading to a rapid increase in mHLA-DR expression (83.1%). Conclusions Severe ARDS in a COVID-19 patient has a deep reduction in mHLA-DR expression concomitantly with secondary infections. The unique IFNy injection was safe and led to a sharp increase in the expression of mHLA-DR. Based on immune and infection monitoring, more cases of severe COVID-19 patients with low mHLA-DR should be treated by IFNy to test the clinical effectiveness.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2021.645124
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 2
    Online Resource
    Online Resource
    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-8-22)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-8-22)
    Abstract: Mucormycosis is a deadly fungal infection that mainly affects severely immunocompromised patients. We report herein the case of a previously immunocompetent adult woman who developed invasive cutaneous mucormycosis after severe burn injuries. Interferon-gamma (IFN-γ) treatment was added after failure of conventional treatment and confirmation of a sustained profound immunodepression. The diagnosis was based on a reduced expression of HLA-DR on monocytes (mHLA-DR), NK lymphopenia and a high proportion of immature neutrophils. The immune-related alterations were longitudinally monitored using panels of immune-related biomarkers. Results Initiation of IFN-γ was associated with a rapid clinical improvement and a subsequent healing of mucormycosis infection, with no residual fungi at the surgical wound repair. The serial immunological assessment showed sharp improvements of immune parameters: a rapid recovery of mHLA-DR and of transcriptomic markers for T-cell proliferation. The patient survived and was later discharged from the ICU. Conclusion The treatment with recombinant IFN-γ participated to the resolution of a progressively invasive mucormycosis infection, with rapid improvement in immune parameters. In the era of precision medicine in the ICU, availability of comprehensive immune monitoring tools could help guiding management of refractory infections and provide rationale for immune stimulation strategies in these high risk patients.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.883638
    DOI: 10.3389/fimmu.2022.883638.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
    Online Resource
    Online Resource
    Table_3.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-10-29)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-10-29)
    Abstract: Objectives: To investigate the association of plasma LPS mass with mortality and inflammation in patients with peritonitis-induced septic shock (SS). Design: Longitudinal endotoxin and inflammatory parameters in a multicentric cohort of SS. Patients: Protocolized post-operative parameters of 187 SS patients collected at T1 (12 h max post-surgery) and T4 (24 h after T1). Intervention: Post-hoc analysis of ABDOMIX trial. Measurements and Results: Plasma concentration of LPS mass as determined by HPLC-MS/MS analysis of 3-hydroxymyristate, activity of phospholipid transfer protein (PLTP), lipids, lipoproteins, IL-6, and IL-10. Cohort was divided in low (LLPS) and high (HLPS) LPS levels. The predictive value for mortality was tested by multivariate analysis. HLPS and LLPS had similar SAPSII (58 [48.5; 67]) and SOFA (8 [6.5; 9] ), but HLPS showed higher death and LPS to PLTP ratio ( p & lt; 0.01). LPS was stable in HLPS, but it increased in LLPS with a greater decrease in IL-6 ( p & lt; 0.01). Dead patients had a higher T1 LPS ( p = 0.02), IL-6 ( & lt;0.01), IL-10 (=0.01), and day 3 SOFA score ( p = 0.01) than survivors. In the group of SAPSII & gt; median, the risk of death in HLPS (38%) was higher than in LLPS (24%; p & lt; 0.01). The 28-day death was associated only with SAPSII (OR 1.06 [1.02; 1.09]) and HLPS (OR 2.47 [1; 6.11] ) in the multivariate model. In HLPS group, high PLTP was associated with lower plasma levels of IL-6 ( p = 0.02) and IL-10 ( p = 0.05). Conclusions: Combination of high LPS mass concentration and high SAPS II is associated with elevated mortality in peritonitis-induced SS patients.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2021.749405
    DOI: 10.3389/fmed.2021.749405.s001
    DOI: 10.3389/fmed.2021.749405.s002
    DOI: 10.3389/fmed.2021.749405.s003
    DOI: 10.3389/fmed.2021.749405.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 4
    Online Resource
    Online Resource
    Case Report: Intercurrent infections in COVID-19-induced sustained immunodepression: is interferon gamma a suitable drug?
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-6-8)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-6-8)
    Abstract: Acute immuno-depression syndrome (AIDs) had been observed in many life-threatening conditions leading to the Intensive Care Unit. and is associated with recurrent secondary infections. We report one COVID-19 patient with a severe ARDS, demonstrating acute immunodepression syndrome lasting for several weeks. The occurrence of secondary infections despite long treatment by antibiotics led to combined interferon γ (IFNγ) as reported previously. The response to IFNγ was evaluated by the flowcytometry HLA-DR expression on circulating monocytes, which was repeated from time to time. The severe COVID-19 patients responded well to IFNγ without adverse events.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2023.1183665
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 5
    Online Resource
    Online Resource
    DataSheet_1.docx
    Frontiers Media SA ; 2020
    In:  Frontiers in Immunology Vol. 11 ( 2020-10-23)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2020-10-23)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2020.580250
    DOI: 10.3389/fimmu.2020.580250.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606827-8
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  • 6
    Online Resource
    Online Resource
    Case Report: Interferon- γ Rescues Monocytic Human Leukocyte Antigen Receptor (mHLA-DR) Function in a COVID-19 Patient With ARDS and Superinfection With Multiple MDR 4MRGN Bacterial Strains
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-11-1)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-11-1)
    Abstract: CD14+ monocytes present antigens to adaptive immune cells via monocytic human leukocyte antigen receptor (mHLA-DR), which is described as an immunological synapse. Reduced levels of mHLA-DR can display an acquired immune defect, which is often found in sepsis and predisposes for secondary infections and fatal outcomes. Monocytic HLA-DR expression is reliably induced by interferon- γ (IFNγ) therapy. Case Report We report a case of multidrug-resistant superinfected COVID-19 acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support. The resistance profiles of the detected Klebsiella pneumoniae , Pseudomonas aeruginosa, Acinetobacter baumannii and Citrobacter freundii isolates were equipped with resistance to all four antibiotic classes including carbapenems (4MRGN) and Cefiderocol in the case of K. pneumoniae . A causal therapeutic antibiotic strategy was not available. Therefore, we measured the immune status of the patient aiming to identify a potential acquired immune deficiency. Monocyte HLA-DR expression identified by FACS analysis revealed an expression level of 34% positive monocytes and suggested severe immunosuppression. We indicated IFNγ therapy, which resulted in a rapid increase in mHLA-DR expression (96%), rapid resolution of invasive bloodstream infection, and discharge from the hospital on day 70. Discussion Superinfection is a dangerous complication of COVID-19 pneumonia, and sepsis-induced immunosuppression is a risk factor for it. Immunosuppression is expressed by a disturbed antigen presentation of monocytes to cells of the adaptive immune system. The case presented here is remarkable as no validated antibiotic regimen existed against the detected bacterial pathogens causing bloodstream infection and severe pneumonia in a patient suffering from COVID-19 ARDS. Possible restoration of the patient’s own immunity by IFNγ was a plausible option to boost the patient’s immune system, eliminate the identified 4MRGNs, and allow for lung recovery. This led to the conclusion that immune status monitoring is useful in complicated COVID-19-ARDS and that concomitant IFNγ therapy may support antibiotic strategies. Conclusion After a compromised immune system has been detected by suppressed mHLA-DR levels, the immune system can be safely reactivated by IFNγ.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2021.753849
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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