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  1. Article ; Online: Herpes simplex virus encephalitis of childhood: inborn errors of central nervous system cell-intrinsic immunity.

    Zhang, Shen-Ying

    Human genetics

    2020  Volume 139, Issue 6-7, Page(s) 911–918

    Abstract: Herpes simplex virus 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in Western countries. Over the last 15 years, human genetic and immunological studies have provided proof-of-principle that childhood HSE can result from ... ...

    Abstract Herpes simplex virus 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in Western countries. Over the last 15 years, human genetic and immunological studies have provided proof-of-principle that childhood HSE can result from inborn errors of central nervous system (CNS)-specific, cell-intrinsic immunity to HSV-1. HSE-causing mutations of eight genes disrupt known (TLR3-dependent IFN-α/β immunity) and novel (dependent on DBR1 or snoRNA31) antiviral mechanisms. Monogenic inborn errors confer susceptibility to forebrain (TLR3-IFN or snoRNA31) or brainstem (DBR1) HSE. Most of these disorders display incomplete clinical penetrance, with the possible exception of DBR1 deficiency. They account for a small, but non-negligible proportion of cases (about 7%). These findings pave the way for the gradual definition of the genetic and immunological architecture of childhood HSE, with both biological and clinical implications.
    MeSH term(s) Central Nervous System Diseases/epidemiology ; Central Nervous System Diseases/genetics ; Central Nervous System Diseases/immunology ; Central Nervous System Diseases/virology ; Child ; Encephalitis, Herpes Simplex/epidemiology ; Encephalitis, Herpes Simplex/genetics ; Encephalitis, Herpes Simplex/immunology ; Encephalitis, Herpes Simplex/virology ; Genetic Predisposition to Disease ; Herpes Simplex/complications ; Herpes Simplex/immunology ; Herpes Simplex/virology ; Herpesvirus 1, Human/immunology ; Herpesvirus 1, Human/pathogenicity ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Cellular/immunology ; Mutation
    Language English
    Publishing date 2020-02-10
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 223009-4
    ISSN 1432-1203 ; 0340-6717
    ISSN (online) 1432-1203
    ISSN 0340-6717
    DOI 10.1007/s00439-020-02127-5
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  2. Article: Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma.

    Wu, Xuan / Yang, Shen-Ying / Zhang, Yi-Hua / Fang, Jin-Zhou / Wang, Shuai / Xu, Zhi-Wei / Zhang, Xiao-Ju

    World journal of clinical oncology

    2024  Volume 15, Issue 1, Page(s) 45–61

    Abstract: Background: Heat shock protein A4 (HSPA4) belongs to molecular chaperone protein family which plays important roles within variable cellular activities, including cancer initiation and progression. However, the prognostic and immunological significance ... ...

    Abstract Background: Heat shock protein A4 (HSPA4) belongs to molecular chaperone protein family which plays important roles within variable cellular activities, including cancer initiation and progression. However, the prognostic and immunological significance of HSPA4 in lung adenocarcinoma (LUAD) has not been revealed yet.
    Aim: To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.
    Methods: We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database. The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test. Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors, including HSPA4, in LUAD. Gene set enrichment analysis (GSEA) was conducted to identify the key signaling pathways associated with HSPA4. The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA).
    Results: Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage, advanced pathologic stage, progression disease status of primary therapy outcome and female subgroups with LUAD. In addition, increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival. GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response, particularly through diminishing the function of cytotoxicity cells and CD8 T cells. The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells, while a negative correlation was observed with cytotoxic cell infiltration levels.
    Conclusion: Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2587357-X
    ISSN 2218-4333
    ISSN 2218-4333
    DOI 10.5306/wjco.v15.i1.45
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  3. Article ; Online: Type I interferons and SARS-CoV-2: from cells to organisms.

    Bastard, Paul / Zhang, Qian / Zhang, Shen-Ying / Jouanguy, Emmanuelle / Casanova, Jean-Laurent

    Current opinion in immunology

    2022  Volume 74, Page(s) 172–182

    Abstract: Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type I IFNs and SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of type I IFNs, and SARS-CoV-2 proteins can inhibit various ... ...

    Abstract Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type I IFNs and SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of type I IFNs, and SARS-CoV-2 proteins can inhibit various steps in type I IFN production and response. Exogenous type I IFNs inhibit viral growth in vitro. In various animal species infected in vivo, type I IFN deficiencies underlie higher viral loads and more severe disease than in control animals. The early administration of exogenous type I IFNs improves infection control. In humans, inborn errors of, and auto-antibodies against type I IFNs underlie life-threatening COVID-19 pneumonia. Overall, type I IFNs are essential for host defense against SARS-CoV-2 in individual cells and whole organisms.
    MeSH term(s) Animals ; COVID-19/immunology ; Humans ; Interferon Type I/immunology ; SARS-CoV-2/immunology
    Chemical Substances Interferon Type I
    Language English
    Publishing date 2022-01-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2022.01.003
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  4. Article ; Online: Neuron-intrinsic immunity to viruses in mice and humans.

    Zhang, Shen-Ying / Harschnitz, Oliver / Studer, Lorenz / Casanova, Jean-Laurent

    Current opinion in immunology

    2021  Volume 72, Page(s) 309–317

    Abstract: Viral encephalitis is a major neglected medical problem. Host defense mechanisms against viral infection of the central nervous system (CNS) have long remained unclear. The few previous studies of CNS-specific immunity to viruses in mice in vivo and ... ...

    Abstract Viral encephalitis is a major neglected medical problem. Host defense mechanisms against viral infection of the central nervous system (CNS) have long remained unclear. The few previous studies of CNS-specific immunity to viruses in mice in vivo and humans in vitro have focused on the contributions of circulating leukocytes, resident microglial cells and astrocytes, with neurons long considered passive victims of viral infection requiring protection from extrinsic antiviral mechanisms. The last decade has witnessed the gradual emergence of the notion that neurons also combat viruses through cell-intrinsic mechanisms. Forward genetic approaches in humans have shown that monogenic inborn errors of TLR3, IFN-α/β, or snoRNA31 immunity confer susceptibility to herpes simplex virus 1 (HSV-1) infection of the forebrain, whereas inborn errors of DBR1 underlie brainstem infections due to various viruses, including HSV-1. The study of human pluripotent stem cell (hPSC)-derived CNS-resident cells has unraveled known (i.e. TLR3-dependent IFN-α/β immunity) and new (i.e. snoRNA31-dependent or DBR1-dependent immunity) cell-intrinsic antiviral mechanisms operating in neurons. Reverse genetic approaches in mice have confirmed that some known antiviral mechanisms also operate in mouse neurons (e.g. TLR3 and IFN-α/β immunity). The search for human inborn errors of immunity (IEIs) underlying various forms of viral encephalitis, coupled with mouse models in vivo, and hPSC-based culture models of CNS and peripheral nervous system cells and organoids in vitro, should shed further light on the cell-specific and tissue-specific mechanisms of host defense against viruses in the human brain.
    MeSH term(s) Animals ; Biomarkers ; Central Nervous System Viral Diseases/etiology ; Disease Resistance/genetics ; Disease Resistance/immunology ; Disease Susceptibility/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Interferon Type I/metabolism ; Mice ; Neurons/immunology ; Neurons/virology ; Rats ; Species Specificity ; Toll-Like Receptor 3/metabolism ; Virus Diseases/etiology
    Chemical Substances Biomarkers ; Interferon Type I ; TLR3 protein, human ; Toll-Like Receptor 3
    Language English
    Publishing date 2021-08-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2021.07.004
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  5. Article ; Online: La panencéphalite sclérosante subaiguë de la rougeole - Une maladie mortelle encore présente et toujours mystérieuse.

    Lebon, Pierre / Gelot, Antoinette / Zhang, Shen-Ying / Casanova, Jean-Laurent / Hauw, Jean-Jacques

    Medecine sciences : M/S

    2022  Volume 38, Issue 6-7, Page(s) 553–561

    Abstract: Subacute sclerosing panencephalitis, a late complication of measles, is still present during epidemics of this disease due to insufficient vaccination. After a historical review, the importance of the diagnostic criteria and the pathophysiology of SSEP ... ...

    Title translation Measles subacute sclerosing panencephalitis (SSPE): A still present and still mysterious fatal disease. History, Diagnosis and Assumptions.
    Abstract Subacute sclerosing panencephalitis, a late complication of measles, is still present during epidemics of this disease due to insufficient vaccination. After a historical review, the importance of the diagnostic criteria and the pathophysiology of SSEP are discussed. Numerous studies on the parameters of innate immunity and interferon responses tend to show a decrease in the activity of cellular immunity. Several hypotheses are formulated based on the publications of the different forms of the disease: Congenital, perinatal, forms with short incubation similar to acute inclusion encephalitis (AIE), rapidly evolving forms, forms of the immunocompromised, or even adults. Familial forms have been identified, suggesting a genetic cause. Based on the duration of the latency period, two groups have been individualized, prompting a retrospective and prospective analysis of the exomes of these patients. The knowledge of the genes involved should be useful for the understanding of the pathophysiology of SSPE and other late neurological RNA virus infections.
    MeSH term(s) Adult ; Female ; Humans ; Measles/diagnosis ; Measles/epidemiology ; Measles virus/genetics ; Pregnancy ; Retrospective Studies ; Subacute Sclerosing Panencephalitis/diagnosis ; Subacute Sclerosing Panencephalitis/etiology ; Vaccination
    Language French
    Publishing date 2022-06-29
    Publishing country France
    Document type Journal Article
    ZDB-ID 632733-3
    ISSN 1958-5381 ; 0767-0974
    ISSN (online) 1958-5381
    ISSN 0767-0974
    DOI 10.1051/medsci/2022081
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  6. Article ; Online: Human autoantibodies neutralizing type I IFNs: From 1981 to 2023.

    Bastard, Paul / Gervais, Adrian / Le Voyer, Tom / Philippot, Quentin / Cobat, Aurélie / Rosain, Jérémie / Jouanguy, Emmanuelle / Abel, Laurent / Zhang, Shen-Ying / Zhang, Qian / Puel, Anne / Casanova, Jean-Laurent

    Immunological reviews

    2024  Volume 322, Issue 1, Page(s) 98–112

    Abstract: Human autoantibodies (auto-Abs) neutralizing type I IFNs were first discovered in a woman with disseminated shingles and were described by Ion Gresser from 1981 to 1984. They have since been found in patients with diverse conditions and are even used as ... ...

    Abstract Human autoantibodies (auto-Abs) neutralizing type I IFNs were first discovered in a woman with disseminated shingles and were described by Ion Gresser from 1981 to 1984. They have since been found in patients with diverse conditions and are even used as a diagnostic criterion in patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1). However, their apparent lack of association with viral diseases, including shingles, led to wide acceptance of the conclusion that they had no pathological consequences. This perception began to change in 2020, when they were found to underlie about 15% of cases of critical COVID-19 pneumonia. They have since been shown to underlie other severe viral diseases, including 5%, 20%, and 40% of cases of critical influenza pneumonia, critical MERS pneumonia, and West Nile virus encephalitis, respectively. They also seem to be associated with shingles in various settings. These auto-Abs are present in all age groups of the general population, but their frequency increases with age to reach at least 5% in the elderly. We estimate that at least 100 million people worldwide carry auto-Abs neutralizing type I IFNs. Here, we briefly review the history of the study of these auto-Abs, focusing particularly on their known causes and consequences.
    MeSH term(s) Female ; Humans ; Aged ; Autoantibodies ; Interferon Type I ; COVID-19 ; Polyendocrinopathies, Autoimmune ; Herpes Zoster
    Chemical Substances Autoantibodies ; Interferon Type I
    Language English
    Publishing date 2024-01-09
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13304
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  7. Article ; Online: Severe COVID-19 in the young and healthy: monogenic inborn errors of immunity?

    Zhang, Shen-Ying / Zhang, Qian / Casanova, Jean-Laurent / Su, Helen C

    Nature reviews. Immunology

    2020  Volume 20, Issue 8, Page(s) 455–456

    MeSH term(s) Betacoronavirus/immunology ; COVID-19 ; Coronavirus Infections/immunology ; Genetic Diseases, Inborn/immunology ; Humans ; Immunity/immunology ; Pandemics ; Pneumonia, Viral/immunology ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-05-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-020-0373-7
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  8. Article ; Online: Correction to: IFN-α2a Therapy in Two Patients with Inborn Errors of TLR3 and IRF3 Infected with SARS-CoV-2.

    Lévy, Romain / Bastard, Paul / Lanternier, Fanny / Lecuit, Marc / Zhang, Shen-Ying / Casanova, Jean-Laurent

    Journal of clinical immunology

    2021  Volume 41, Issue 1, Page(s) 28

    Language English
    Publishing date 2021-01-20
    Publishing country Netherlands
    Document type Published Erratum
    ZDB-ID 779361-3
    ISSN 1573-2592 ; 0271-9142
    ISSN (online) 1573-2592
    ISSN 0271-9142
    DOI 10.1007/s10875-021-00969-w
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  9. Article ; Online: Regarding the efficacy of the COVID-19 vaccine in pediatric systemic lupus erythematosus patient.

    Cui, Weibo / Zhang, Ying / Shen, Yuhuan

    Lupus

    2024  Volume 33, Issue 3, Page(s) 312–313

    MeSH term(s) Child ; Humans ; COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/drug therapy
    Chemical Substances COVID-19 Vaccines
    Language English
    Publishing date 2024-01-15
    Publishing country England
    Document type Letter
    ZDB-ID 1154407-7
    ISSN 1477-0962 ; 0961-2033
    ISSN (online) 1477-0962
    ISSN 0961-2033
    DOI 10.1177/09612033241227028
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  10. Article ; Online: IFN-α2a Therapy in Two Patients with Inborn Errors of TLR3 and IRF3 Infected with SARS-CoV-2.

    Lévy, Romain / Bastard, Paul / Lanternier, Fanny / Lecuit, Marc / Zhang, Shen-Ying / Casanova, Jean-Laurent

    Journal of clinical immunology

    2021  Volume 41, Issue 1, Page(s) 26–27

    MeSH term(s) Adult ; COVID-19/diagnosis ; COVID-19/drug therapy ; COVID-19/immunology ; COVID-19/virology ; Female ; Humans ; Interferon Regulatory Factor-3/deficiency ; Interferon Regulatory Factor-3/genetics ; Interferon Type I/immunology ; Interferon Type I/metabolism ; Interferon-alpha/therapeutic use ; Polyethylene Glycols/therapeutic use ; Primary Immunodeficiency Diseases/complications ; Primary Immunodeficiency Diseases/genetics ; Primary Immunodeficiency Diseases/immunology ; Recombinant Proteins/therapeutic use ; SARS-CoV-2/immunology ; SARS-CoV-2/isolation & purification ; Toll-Like Receptor 3/deficiency ; Toll-Like Receptor 3/genetics ; Treatment Outcome
    Chemical Substances IRF3 protein, human ; Interferon Regulatory Factor-3 ; Interferon Type I ; Interferon-alpha ; Recombinant Proteins ; TLR3 protein, human ; Toll-Like Receptor 3 ; Polyethylene Glycols (3WJQ0SDW1A) ; peginterferon alfa-2a (Q46947FE7K)
    Language English
    Publishing date 2021-01-03
    Publishing country Netherlands
    Document type Case Reports ; Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 779361-3
    ISSN 1573-2592 ; 0271-9142
    ISSN (online) 1573-2592
    ISSN 0271-9142
    DOI 10.1007/s10875-020-00933-0
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