scholarly journals Neutralizing Anti-interferon-γ Autoantibodies; An Ameliorating Factor in COVID-19 Infection?

2021 ◽  
Author(s):  
Mark Kacar ◽  
Paulina Cortes-Acevedo ◽  
Vinesh Patel ◽  
Clive Carter ◽  
Pamela Hughes ◽  
...  
Keyword(s):  
Bone Marrow Examination ◽  
Interferon Γ ◽  
High Titre ◽  
Igg Antibody ◽  
Disease States ◽  
Care Workers ◽  
Recovery Assay ◽  
Mycobacterium Avium Intracellulare ◽  
Ifn Γ ◽  
The Impact

Abstract Background: Elevated levels of interferon-gamma (IFNγ) have been found in COVID-19 infection, however its role in this setting remains poorly understood. Cases of non-tuberculous mycobacterium (NTM) infections due to anti-IFNγ autoantibodies (Ab) were first reported in 2004. NTM and COVID-19 co-infection in a patient with acquired IFNγ deficiency has not previously been described. The impact of anti-IFNγ Ab on the severity of COVID-19 has not been previously explored. Objective: We report a case of COVID-19 infection in a patient hospitalised with NTM infection due to acquired IFNγ deficiency caused by anti-IFNγ Ab. We also explore effects of IFNγ Ab on the severity of COVID-19 infection. Methods: Detailed immunological investigations were performed. Bio-rad, Bio-Plex methodology was used to detect anti-IFNγ Ab, titration, IFNγ recovery assay and SARS-CoV-2 serology. Anti-IFNγ Ab were tested in patients with severe (COV-Pat) and health care workers with mild/asymptomatic COVID-19 infection (COV-Asx). Results: Mycobacterium avium intracellulare was diagnosed following bone marrow examination and culture. High titre anti-IFNγ Ab were detected in patient’s serum. The autoantibodies neutralized both endogenously produced and exogenously administered IFNγ. SARS-COV-2 infection was identified during routine inpatient testing. Despite prolonged SARS-COV-2 infection the patient showed only minimal additional symptoms, never developed any significant inflammatory complications and eventually mounted an adequate IgG antibody response to the SARS-COV-2 trimeric S-protein. Elevated titres of anti-IFNγ Ab were detected in COV-Pat and COV-Asx, compared to non-infected healthy controls. The titres were broadly similar between COV-Pat and COV-Asx groups, but much lower compared to patients with acquired IFNγ Ab deficiency. Conclusion: IFN-γ is known to play a central role in hyperinflammatory disease states such as macrophage activation syndrome This study illustrates the potential value of inhibiting IFNγ to prevent pathological inflammatory response to COVID-19.

scholarly journals Checks and balances between human cytomegalovirus replication and indoleamine-2,3-dioxygenase

2014 ◽  
Vol 95 (3) ◽  
pp. 659-670 ◽  
Author(s):  
Albert Zimmermann ◽  
Sebastian Hauka ◽  
Marco Maywald ◽  
Vu Thuy Khanh Le ◽  
Silvia K. Schmidt ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Cell Types ◽  
Interferon Γ ◽  
Counter Measures ◽  
Indoleamine 2,3 Dioxygenase ◽  
Infected Cells ◽  
Hcmv Replication ◽  
Ifn Γ ◽  
The Impact

Despite a rigorous blockade of interferon-γ (IFN-γ) signalling in infected fibroblasts as a mechanism of immune evasion by human cytomegalovirus (HCMV), IFN-γ induced indoleamine-2,3-dioxygenase (IDO) has been proposed to represent the major antiviral restriction factor limiting HCMV replication in epithelial cells. Here we show that HCMV efficiently blocks transcription of IFN-γ-induced IDO mRNA both in infected fibroblasts and epithelial cells even in the presence of a preexisting IFN-induced antiviral state. This interference results in severe suppression of IDO bioactivity in HCMV-infected cells and restoration of vigorous HCMV replication. Depletion of IDO expression nonetheless substantially alleviated the antiviral impact of IFN-γ treatment in both cell types. These findings highlight the effectiveness of this IFN-γ induced effector gene in restricting HCMV productivity, but also the impact of viral counter-measures.

Graft-versus-host disease causes failure of donor hematopoiesis and lymphopoiesis in interferon-γ receptor-deficient hosts

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 2111-2119 ◽  
Author(s):  
Jean-Sébastien Delisle ◽  
Louis Gaboury ◽  
Marie-Pier Bélanger ◽  
Éliane Tassé ◽  
Hideo Yagita ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Hematopoietic Cells ◽  
Interferon Γ ◽  
Host Cells ◽  
Type I ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor Cells ◽  
Ifn Γ ◽  
The Impact

Abstract The immunopathologic condition known as graft-versus-host disease (GVHD) results from a type I T-cell process. However, a prototypical type I cytokine, interferon-γ (IFN-γ), can protect against several manifestations of GVHD in recipients of major histocompatibility complex (MHC)–mismatched hematopoietic cells. We transplanted hematopoietic cells from C3H.SW donors in wild-type (wt) and IFN-γ-receptor–deficient (IFN-γRKO) MHC-matched C57BL/6 recipients. In IFN-γRKO recipients, host cells were unresponsive to IFN-γ, whereas wt donor cells were exposed to exceptionally high levels of IFN-γ. From an IFN-γ perspective, we could therefore evaluate the impact of a loss-of-function on host cells and gain-of-function on donor cells. We found that lack of IFN-γR prevented up-regulation of MHC proteins on host cells but did not mitigate damage to most target organs. Two salient phenotypes in IFN-γRKO recipients involved donor cells: lymphoid hypoplasia and hematopoietic failure. Lymphopenia was due to FasL-induced apoptosis and decreased cell proliferation. Bone marrow aplasia resulted from a decreased proliferation of hematopoietic stem/progenitor cells that was associated with down-regulation of 2 genes negatively regulated by IFN-γ: Ccnd1 and Myc. We conclude that IFN-γ produced by alloreactive T cells may entail a severe graft-versus-graft reaction and could be responsible for cytopenias that are frequently observed in subjects with GVHD.

Estimation of incidence of tuberculosis infection in health-care workers using repeated interferon-γ assays

2009 ◽  
Vol 137 (12) ◽  
pp. 1691-1698 ◽  
Author(s):  
T. YOSHIYAMA ◽  
N. HARADA ◽  
K. HIGUCHI ◽  
Y. NAKAJIMA ◽  
H. OGATA
Keyword(s):  
Health Care ◽  
Logistic Regression ◽  
Mycobacterium Tuberculosis ◽  
Regression Analysis ◽  
Health Care Workers ◽  
Interferon Γ ◽  
Multivariable Logistic Regression Analysis ◽  
Cross Sectional ◽  
Care Workers ◽  
Ifn Γ

SUMMARYThe aim was to estimate the incidence of Mycobacterium tuberculosis (Mtb) infection in health-care workers (HCWs) in Japan. We repeated cross-sectional surveys of HCWs with QuantiFERON®-TB Gold (QFT-G) in 2003, 2005 and 2007 at a hospital with tuberculosis (TB) wards, and 311 HCWs who underwent QFT-G testing two or three times were included in the study. Five HCWs (1·8%) converted from negative to positive. Incidence of new TB infection was estimated to be 0·6/100 person-years by the CDC's definition. Thirteen positive persons (41%) reverted from positive to negative. Multivariable logistic regression analysis identified a significant association between QFT-G conversion and working in TB wards. The IFN-γ levels of all but two subjects with reverting or converting QFT-G results were close to the test's cut-off. The incidence of Mtb infection in HCWs at our hospital was higher than that estimated for the general population in Japan. Criteria for defining QFT-G conversion and reversion need further investigation considering the high proportion of reversion, as the incidence of infection would have changed if we had applied other definitions.

scholarly journals Interferon-γ is increased in the gut of patients with irritable bowel syndrome and modulates serotonin metabolism

2016 ◽  
Vol 310 (6) ◽  
pp. G439-G447 ◽  
Author(s):  
Maria Raffaella Barbaro ◽  
Antonio Di Sabatino ◽  
Cesare Cremon ◽  
Paolo Giuffrida ◽  
Michelangelo Fiorentino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Irritable Bowel Syndrome ◽  
Colonic Mucosa ◽  
Interferon Γ ◽  
Serotonin Metabolism ◽  
Ifn Γ ◽  
Irritable Bowel ◽  
The Impact

Mucosal immune activation and altered serotonin metabolism participate in the pathophysiology of irritable bowel syndrome (IBS). However, the reciprocal interplay between these two systems remains unknown. We evaluated the expression and release of interferon (IFN)-γ from the colonic mucosa of patients with IBS and its impact on serotonin reuptake transporter ( SERT) gene expression in Caco-2 cells. qPCR was used to evaluate IFN-γ gene expression in colonic mucosal biopsies, whereas IFN-γ protein amount was assessed by ELISA. Colonic T box expressed in T cells (T-bet) and phosphorylated signal transducer and activator of transcription 4 protein amount were evaluated by Western blot. The impact of colonic mucosal mediators on SERT gene expression was evaluated in Caco-2 cells using qPCR. IFN-γ receptor was silenced in Caco-2 cells to determine the effect of IFN-γ released by mucosal biopsies. Compared with asymptomatic controls (ACs), the expression of IFN-γ gene and its transcription factor T-bet were markedly increased in the colonic mucosa of patients with IBS. Compared with ACs, IFN-γ protein tissue levels and its release by mucosal biopsies were significantly increased in IBS. The exposure of Caco-2 cells to IBS supernatants induced a significant decrease in SERT gene expression, independently of IBS subtypes, compared with AC mucosal supernatants. In Caco-2 cells, IFN-γ receptor silencing reversed the reduction of SERT expression evoked by IBS supernatants vs. nonsilenced cell lines. IFN-γ gene, its transcription factor T-bet, IFN-γ protein expression, and its release are increased in the colonic mucosa of patients with IBS and downregulate SERT gene expression in vitro. These results suggest that IFN-γ downregulates SERT expression, hence likely playing a role in altered serotonin metabolism of patients with IBS.

scholarly journals Impact of interferon-γ on hematopoiesis

Blood ◽  
2014 ◽  
Vol 124 (16) ◽  
pp. 2479-2486 ◽  
Author(s):  
Alexander M. de Bruin ◽  
Carlijn Voermans ◽  
Martijn A. Nolte
Keyword(s):  
Interferon Γ ◽  
Cytokine Signaling ◽  
Tumor Control ◽  
Strong Impact ◽  
Hematopoietic Stem ◽  
Physiological Processes ◽  
Ifn Γ ◽  
Novel Concept ◽  
Intracellular Infections ◽  
The Impact

Abstract The proinflammatory cytokine interferon-γ (IFN-γ) is well known for its important role in innate and adaptive immunity against intracellular infections and for tumor control. Yet, it has become clear that IFN-γ also has a strong impact on bone marrow (BM) output during inflammation, as it affects the differentiation of most hematopoietic progenitor cells. Here, we review the impact of IFN-γ on hematopoiesis, including the function of hematopoietic stem cells (HSCs) and more downstream progenitors. We discuss which hematopoietic lineages are functionally modulated by IFN-γ and through which underlying molecular mechanism(s). We propose the novel concept that IFN-γ acts through upregulation of suppressor of cytokine signaling molecules, which impairs signaling of several cytokine receptors. IFN-γ has also gained clinical interest from different angles, and we discuss how chronic IFN-γ production can lead to the development of anemia and BM failure and how it is involved in malignant hematopoiesis. Overall, this review illustrates the wide-ranging effect of IFN-γ on the (patho-)physiological processes in the BM.

A Study On Impact Of Work Life Related Factors On Employee Engagement In Health Care Sector Workers In Dindigul District.

2019 ◽  
Vol 118 (7) ◽  
pp. 20-26
Author(s):  
S. JAYARAMAN ◽  
R. Sindhya ◽  
P. Vijiyalakshmi
Keyword(s):  
Health Care ◽  
Path Analysis ◽  
Employee Engagement ◽  
Health Care Workers ◽  
Health Care Sector ◽  
Work Life ◽  
Primary Data ◽  
Related Factors ◽  
Care Workers ◽  
The Impact

this research aims to find out the intensity of Employee Engagement of the health care sector workers and the relationship between the Work life factors and Employee Engagement of Health care sector workers in Dindigul District. Primary data were used in this research, were collected from 298 Health care workers from Dindigul District. Questionnaire was the major tool used to gather the primary data from the selected sample respondents. For this purpose, a well structured questionnaire was constructed with the help of professionals and the practiced employees of various health care units in Dindigul District. The health care employees were chosen by simple random sampling method. The investigative measures of regression Path analysis, and simple percentage analysis were utilized to find the impact of work life related factors with the Employee Engagement. The maximum Health care workers were generally satisfied with their jobs. The analytical procedure of path analysis multiple regressions was utilized to determine the predicting strength among Work life factors and the employee engagement. This study provides an another view about the importance of Work life factors and Employee engagement for organizational effectiveness and performance .

Self-assessment by medical workers of the degree of influence of working conditions on the development of occupational diseases

2019 ◽  
pp. 463-467 ◽  
Author(s):  
N. N. Petrukhin ◽  
O. N. Andreenko ◽  
I. V. Boyko ◽  
S. V. Grebenkov
Keyword(s):  
Health Care ◽  
Working Conditions ◽  
Occupational Diseases ◽  
Health Workers ◽  
Medical Personnel ◽  
Long Term Memory ◽  
Self Assessment ◽  
Medical Institutions ◽  
Care Workers ◽  
The Impact

Introduction. The activities of health workers are associated with the impact of many harmful factors that lead to loss of health. Compared with other professional groups, health care workers are ill longer and harder, which may be due to polymorbidity pathology.The aim of the study based on the survey data to study the representation of health workers about working conditions and to identify their impact on the formation of occupational diseases.Materials and methods. In order to get a real idea of the attitude of medical workers to their working conditions in 2018, an anonymous survey was conducted of 1129 doctors and 776 employees of secondary and junior medical personnel working in health care institutions in St. Petersburg, Moscow, Krasnoyarsk, Vologda and Orel.Results. Research of working conditions and health of physicians allowed to establish that work in medical institutions imposes considerable requirements to an organism of working, its physical condition and endurance, volume of operational and long-term memory, ability to resist to mental, moral and ethical overloads.Conclusions: The most important method of combating the development of occupational diseases is their prevention. Organizational and preventive measures should be aimed primarily at monitoring the working conditions and health of medical staff .

Stress, anxiety, depression and burnout in frontline health care workers during COVID-19 pandemic: a brief systematic review and new data from Russia

2021 ◽  
Author(s):  
Ekaterina Mosolova ◽  
Dmitry Sosin ◽  
Sergey Mosolov
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Female Gender ◽  
Assessment Tools ◽  
Care Workers ◽  
Younger Age ◽  
Wide Range ◽  
Associated Risk Factors ◽  
Anxiety Depression ◽  
The Impact

During the COVID-19 pandemic, healthcare workers (HCWs) have been subject to increased workload while also exposed to many psychosocial stressors. In a systematic review we analyze the impact that the pandemic has had on HCWs mental state and associated risk factors. Most studies reported high levels of depression and anxiety among HCWs worldwide, however, due to a wide range of assessment tools, cut-off scores, and number of frontline participants in the studies, results were difficult to compare. Our study is based on two online surveys of 2195 HCWs from different regions of Russia during spring and autumn epidemic outbreaks revealed the rates of anxiety, stress, depression, emotional exhaustion and depersonalization and perceived stress as 32.3%, 31.1%, 45.5%, 74.2%, 37.7% ,67.8%, respectively. Moreover, 2.4% of HCWs reported suicidal thoughts. The most common risk factors include: female gender, nurse as an occupation, younger age, working for over 6 months, chronic diseases, smoking, high working demands, lack of personal protective equipment, low salary, lack of social support, isolation from families, the fear of relatives getting infected. These results demonstrate the need for urgent supportive programs for HCWs fighting COVID-19 that fall into higher risk factors groups.

Sign in / Sign up

Export Citation Format

Share Document