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  1. Article: Potential Implications of a Type 1 Interferon Gene Signature on COVID-19 Severity and Chronic Inflammation in Sickle Cell Disease.

    Madany, Emaan / Okwan-Duodu, Derick / Balbuena-Merle, Raisa / Hendrickson, Jeanne E / Gibb, David R

    Frontiers in medicine

    2021  Volume 8, Page(s) 679030

    Abstract: At the onset of the corona virus disease 19 (COVID-19) pandemic, there were concerns that patients with sickle cell disease (SCD) might be especially vulnerable to severe sequelae of SARS-CoV-2 infection. While two reports support this conclusion, ... ...

    Abstract At the onset of the corona virus disease 19 (COVID-19) pandemic, there were concerns that patients with sickle cell disease (SCD) might be especially vulnerable to severe sequelae of SARS-CoV-2 infection. While two reports support this conclusion, multiple studies have reported unexpectedly favorable outcomes in patients with SCD. However, mechanisms explaining these disparate conclusions are lacking. Here, we review recent studies indicating that the majority of patients with SCD express elevated levels of anti-viral type 1 interferons (IFNα/β) and interferon stimulated genes, independent of COVID-19, during their baseline state of health. We also present our data from the pre-COVID-19 era, illustrating elevated expression of a well-characterized interferon stimulated gene in a cohort of patients with SCD, compared to race-matched controls. These type 1 interferons and interferon stimulated genes have the potential to contribute to the variable progression of COVID-19 and other viral infections in patients with SCD. While the majority of evidence supports a protective role, the role of IFNα/β in COVID-19 severity in the general population remains an area of current investigation. We conclude that type 1 interferon responses in patients with SCD may contribute to the variable COVID-19 responses reported in prior studies. Additional studies investigating the mechanisms underlying IFNα/β production and other clinical consequences of IFNα/β-mediated inflammation in SCD disease are warranted.
    Language English
    Publishing date 2021-07-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2021.679030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Altered type 1 interferon responses in alloimmunized and nonalloimmunized patients with sickle cell disease.

    Madany, Emaan / Lee, June / Halprin, Chelsea / Seo, Jina / Baca, Nicole / Majlessipour, Fataneh / Hendrickson, Jeanne E / Pepkowitz, Samuel H / Hayes, Chelsea / Klapper, Ellen / Gibb, David R

    EJHaem

    2021  Volume 2, Issue 4, Page(s) 700–710

    Abstract: Patients with sickle cell disease (SCD) have a high prevalence of RBC alloimmunization. However, underlying mechanisms are poorly understood. Given that proinflammatory type 1 interferons ( ... ...

    Abstract Patients with sickle cell disease (SCD) have a high prevalence of RBC alloimmunization. However, underlying mechanisms are poorly understood. Given that proinflammatory type 1 interferons (IFN
    Language English
    Publishing date 2021-07-27
    Publishing country United States
    Document type Journal Article
    ISSN 2688-6146
    ISSN (online) 2688-6146
    DOI 10.1002/jha2.270
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Type 1 Interferon Gene Signature Promotes RBC Alloimmunization in a Lupus Mouse Model.

    Lee, June Young / Madany, Emaan / El Kadi, Najwa / Pandya, Sumaarg / Ng, Kessandra / Yamashita, Michifumi / Jefferies, Caroline A / Gibb, David R

    Frontiers in immunology

    2020  Volume 11, Page(s) 584254

    Abstract: Red blood cell (RBC) transfusion exposes recipients to hundreds of unmatched minor RBC antigens. This exposure can lead to production of alloantibodies that promote clinically significant hemolytic events. Multiple studies have reported an increased ... ...

    Abstract Red blood cell (RBC) transfusion exposes recipients to hundreds of unmatched minor RBC antigens. This exposure can lead to production of alloantibodies that promote clinically significant hemolytic events. Multiple studies have reported an increased frequency of RBC alloimmunization in patients with autoimmunity. However, cellular and molecular mechanisms that underlie autoimmunity-induced alloimmunization have not been reported. Patients with systemic lupus erythematosus (SLE) have a high frequency of alloimmunization and express a type 1 interferon (IFNα/β) gene signature. Thus, we utilized the pristane-induced lupus mouse model to test the hypothesis that inflammation in lupus promotes RBC alloimmunization, and to examine the potential role of IFNα/β. Intraperitoneal injection of pristane, a hydrocarbon oil, led to autoantibody production, glomerulonephritis, and pulmonary hemorrhage in wild type (WT) mice. Pristane treatment significantly induced serum IFNα and expression of multiple interferon-stimulated genes (ISGs) in peripheral blood and peritoneal fluid cells, including inflammatory macrophages. Following transfusion with allogeneic RBCs expressing the KEL glycoprotein, pristane-treated WT mice produced significantly elevated levels of anti-KEL IgM and anti-KEL IgG, compared to untreated mice. Pristane induced comparable levels of inflammatory cells and cytokines in mice lacking the IFNα/β receptor (IFNAR1
    MeSH term(s) Animals ; Antigens/immunology ; Autoimmunity/genetics ; Autoimmunity/immunology ; Disease Models, Animal ; Erythrocyte Transfusion/methods ; Erythrocytes/immunology ; Inflammation/genetics ; Inflammation/immunology ; Interferon Type I/genetics ; Interferon Type I/immunology ; Isoantibodies/genetics ; Isoantibodies/immunology ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout
    Chemical Substances Antigens ; Interferon Type I ; Isoantibodies
    Language English
    Publishing date 2020-09-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.584254
    Database MEDical Literature Analysis and Retrieval System OnLINE

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