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  1. Article ; Online: Intravenous Anakinra for Macrophage Activation Syndrome May Hold Lessons for Treatment of Cytokine Storm in the Setting of Coronavirus Disease 2019.

    Wampler Muskardin, Theresa L

    ACR open rheumatology

    2020  Volume 2, Issue 5, Page(s) 283–285

    Abstract: Macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) are increasingly recognized as being on a continuum of cytokine storm syndromes, with different initiating pathways culminating in cytotoxic dysfunction and uncontrolled ... ...

    Abstract Macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) are increasingly recognized as being on a continuum of cytokine storm syndromes, with different initiating pathways culminating in cytotoxic dysfunction and uncontrolled activation and proliferation of T lymphocytes and macrophages. The activated immune cells produce large amounts of proinflammatory cytokines, including interleukin 1β (IL)-1β. Management depends on the recognized diagnosis. In the setting of a cytokine storm syndrome and infection, collaborative involvement of specialists, including infectious disease and rheumatology is ideal. Anakinra, a recombinant IL-1 receptor antagonist, has been used subcutaneously and intravenously in pediatric patients and is considered a first-line treatment for MAS and secondary HLH (sHLH) among many pediatric rheumatologists. Previous reports of anakinra used in adults for treatment of MAS or sHLH are limited to subcutaneous administration. In this issue, Moneagudo et al. present a series of adult patients with sHLH treated with intravenous anakinra, including patients in whom subcutaneous anakinra was insufficient. As the authors suggest, there is a potential therapeutic use for anakinra in sHLH or the cytokine storm syndrome triggered by COVID19. Trial design will be key, with the patient subpopulation, timing of intervention, and doses tested important.
    Keywords covid19
    Language English
    Publishing date 2020-05-10
    Publishing country United States
    Document type Journal Article
    ISSN 2578-5745
    ISSN (online) 2578-5745
    DOI 10.1002/acr2.11140
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Intravenous Anakinra for Macrophage Activation Syndrome May Hold Lessons for Treatment of Cytokine Storm in the Setting of Coronavirus Disease 2019

    Wampler Muskardin, Theresa L

    Abstract: Macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) are increasingly recognized as being on a continuum of cytokine storm syndromes, with different initiating pathways culminating in cytotoxic dysfunction and uncontrolled ... ...

    Abstract Macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) are increasingly recognized as being on a continuum of cytokine storm syndromes, with different initiating pathways culminating in cytotoxic dysfunction and uncontrolled activation and proliferation of T lymphocytes and macrophages. The activated immune cells produce large amounts of proinflammatory cytokines, including interleukin 1ß (IL)-1ß. Management depends on the recognized diagnosis. In the setting of a cytokine storm syndrome and infection, collaborative involvement of specialists, including infectious disease and rheumatology is ideal. Anakinra, a recombinant IL-1 receptor antagonist, has been used subcutaneously and intravenously in pediatric patients and is considered a first-line treatment for MAS and secondary HLH (sHLH) among many pediatric rheumatologists. Previous reports of anakinra used in adults for treatment of MAS or sHLH are limited to subcutaneous administration. In this issue, Moneagudo et al. present a series of adult patients with sHLH treated with intravenous anakinra, including patients in whom subcutaneous anakinra was insufficient. As the authors suggest, there is a potential therapeutic use for anakinra in sHLH or the cytokine storm syndrome triggered by COVID19. Trial design will be key, with the patient subpopulation, timing of intervention, and doses tested important.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #291837
    Database COVID19

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  3. Article ; Online: Intravenous Anakinra for Macrophage Activation Syndrome May Hold Lessons for Treatment of Cytokine Storm in the Setting of Coronavirus Disease 2019

    Theresa L. Wampler Muskardin

    ACR Open Rheumatology, Vol 2, Iss 5, Pp 283-

    2020  Volume 285

    Abstract: Macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) are increasingly recognized as being on a continuum of cytokine storm syndromes, with different initiating pathways culminating in cytotoxic dysfunction and uncontrolled ... ...

    Abstract Macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) are increasingly recognized as being on a continuum of cytokine storm syndromes, with different initiating pathways culminating in cytotoxic dysfunction and uncontrolled activation and proliferation of T lymphocytes and macrophages. The activated immune cells produce large amounts of proinflammatory cytokines, including interleukin 1β (IL)‐1β. Management depends on the recognized diagnosis. In the setting of a cytokine storm syndrome and infection, collaborative involvement of specialists, including infectious disease and rheumatology is ideal. Anakinra, a recombinant IL‐1 receptor antagonist, has been used subcutaneously and intravenously in pediatric patients and is considered a first‐line treatment for MAS and secondary HLH (sHLH) among many pediatric rheumatologists. Previous reports of anakinra used in adults for treatment of MAS or sHLH are limited to subcutaneous administration. In this issue, Moneagudo et al. present a series of adult patients with sHLH treated with intravenous anakinra, including patients in whom subcutaneous anakinra was insufficient. As the authors suggest, there is a potential therapeutic use for anakinra in sHLH or the cytokine storm syndrome triggered by COVID19. Trial design will be key, with the patient subpopulation, timing of intervention, and doses tested important.
    Keywords Diseases of the musculoskeletal system ; RC925-935 ; covid19
    Subject code 610
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Response to: 'Correspondence on 'Anti-inflammatory therapy for COVID-19 infection: the case for colchicine'' by Perricone

    Shah, Binita / Reyes, Aaron Z / Hu, Kelly A / Teperman, Jacob / Wampler Muskardin, Theresa L / Tardif, Jean-Claude / Pillinger, Michael H

    Annals of the rheumatic diseases

    2021  Volume 82, Issue 4, Page(s) e82

    MeSH term(s) Humans ; COVID-19 ; Colchicine/therapeutic use ; Anti-Inflammatory Agents ; SARS-CoV-2
    Chemical Substances Colchicine (SML2Y3J35T) ; Anti-Inflammatory Agents
    Language English
    Publishing date 2021-01-28
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/annrheumdis-2021-219898
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Lessons from precision medicine in rheumatology.

    Wampler Muskardin, Theresa L / Paredes, Jacqueline L / Appenzeller, Simone / Niewold, Timothy B

    Multiple sclerosis (Houndmills, Basingstoke, England)

    2020  Volume 26, Issue 5, Page(s) 533–539

    Abstract: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are two common autoimmune rheumatic diseases that vary in severity, clinical presentation, and disease course between individuals. Molecular and genetic studies of both diseases have ... ...

    Abstract Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are two common autoimmune rheumatic diseases that vary in severity, clinical presentation, and disease course between individuals. Molecular and genetic studies of both diseases have identified candidate genes and molecular pathways that are linked to various disease outcomes and treatment responses. Currently, patients can be grouped into molecular subsets in each disease, and these molecular categories should enable precision medicine approaches to be applied in rheumatic diseases. In this article, we will review key lessons learned about disease heterogeneity and molecular characterization in rheumatology, which we hope will lead to personalized therapeutic strategies.
    MeSH term(s) Autoimmune Diseases/diagnosis ; Autoimmune Diseases/genetics ; Autoimmune Diseases/immunology ; Humans ; Precision Medicine/methods ; Rheumatic Diseases/diagnosis ; Rheumatic Diseases/genetics ; Rheumatic Diseases/immunology ; Rheumatology/methods
    Language English
    Publishing date 2020-01-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1290669-4
    ISSN 1477-0970 ; 1352-4585
    ISSN (online) 1477-0970
    ISSN 1352-4585
    DOI 10.1177/1352458519884249
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Type I interferon in rheumatic diseases.

    Muskardin, Theresa L Wampler / Niewold, Timothy B

    Nature reviews. Rheumatology

    2018  Volume 14, Issue 4, Page(s) 214–228

    Abstract: The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including systemic lupus erythematosus, Sjögren syndrome, myositis, systemic sclerosis, and rheumatoid arthritis. In normal immune responses, type I ... ...

    Abstract The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including systemic lupus erythematosus, Sjögren syndrome, myositis, systemic sclerosis, and rheumatoid arthritis. In normal immune responses, type I interferons have a critical role in the defence against viruses, yet in many rheumatic diseases, large subgroups of patients demonstrate persistent activation of the type I interferon pathway. Genetic variations in type I interferon-related genes are risk factors for some rheumatic diseases, and can explain some of the heterogeneity in type I interferon responses seen between patients within a given disease. Inappropriate activation of the immune response via Toll-like receptors and other nucleic acid sensors also contributes to the dysregulation of the type I interferon pathway in a number of rheumatic diseases. Theoretically, differences in type I interferon activity between patients might predict response to immune-based therapies, as has been demonstrated for rheumatoid arthritis. A number of type I interferon and type I interferon pathway blocking therapies are currently in clinical trials, the results of which are promising thus far. This Review provides an overview of the many ways in which the type I interferon system affects rheumatic diseases.
    MeSH term(s) Antirheumatic Agents/pharmacology ; Antirheumatic Agents/therapeutic use ; Clinical Trials as Topic ; Gene Regulatory Networks ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Humans ; Interferon Type I/metabolism ; Rheumatic Diseases/drug therapy ; Rheumatic Diseases/genetics ; Rheumatic Diseases/immunology ; Signal Transduction/drug effects
    Chemical Substances Antirheumatic Agents ; Interferon Type I
    Language English
    Publishing date 2018-04-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2491532-4
    ISSN 1759-4804 ; 1759-4790
    ISSN (online) 1759-4804
    ISSN 1759-4790
    DOI 10.1038/nrrheum.2018.31
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Regional european genetic ancestry predicts type I interferon level and risk of severe viral infection.

    Nln, Ilona / Shum, Justine / Ghodke-Puranik, Yogita / Tipon, Regine / Triese, Danielle / Amin, Shreyasee / Makol, Ashima / Osborn, Thomas / Chowdhary, Vaidehi / Thanarajasingam, Uma / Wampler Muskardin, Theresa L / Oke, Vilija / Gunnarsson, Iva / Zickert, Agneta / Zervou, Maria I / Boumpas, Dimitrios T / Svenungsson, Elisabet / Goulielmos, George N / Niewold, Timothy B

    QJM : monthly journal of the Association of Physicians

    2024  

    Abstract: Background: Viral infection outcomes vary widely between individuals, ranging from mild symptoms to severe organ failure and death, and it is clear that host genetic factors play a role in this variability. Type I interferon (IFN) is a critical anti- ... ...

    Abstract Background: Viral infection outcomes vary widely between individuals, ranging from mild symptoms to severe organ failure and death, and it is clear that host genetic factors play a role in this variability. Type I interferon (IFN) is a critical anti-viral cytokine, and we have previously noted differences in type I IFN levels between world populations.
    Methods: In this study, we investigate the interrelationship between regional European genetic ancestry, type I IFN levels, and severe viral infection outcomes.
    Results: In cohorts of European ancestry lupus patients living in Europe, we noted higher IFN in the Northwestern populations as compared to Southeastern populations. In an independent cohort of European ancestry lupus patients from the United States with varying proportional regional European genetic admixture, we observed the same Northwest vs. Southeast European ancestry IFN gradient. We developed a model to predict type I IFN level based on regional European ancestry (AUC = 0.73, p = 6.1e-6). Examining large databases containing serious viral outcomes data, we found that lower predicted IFN in the corresponding European country was significantly correlated with increased viral infection fatality rate, including COVID-19, viral hepatitis, and HIV [Correlation coefficients: -0.79 (p = 4e-2), -0.94 (p = 6e-3), and -0.96 (p = 8e-2) respectively].
    Conclusions: This association between predicted type I IFN level and viral outcome severity suggests a potential causal relationship, as greater intrinsic type I IFN is beneficial in host defense against viruses. Genetic testing could provide insight into individual and population level risk of fatality due to viruses prior to infection, across a wide range of viral pathogens.
    Language English
    Publishing date 2024-03-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 1199985-8
    ISSN 1460-2393 ; 0033-5622 ; 1460-2725
    ISSN (online) 1460-2393
    ISSN 0033-5622 ; 1460-2725
    DOI 10.1093/qjmed/hcae052
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Corrigendum: Increase in pediatric recurrent fever evaluations during the first year of the COVID-19 pandemic in North America.

    Mansfield, Leanne M / Lapidus, Sivia K / Romero, Samira Nazzar / Moorthy, Lakshmi N / Adler-Shohet, Felice C / Hollander, Matthew / Cherian, Julie / Twilt, Marinka / Lionetti, Geraldina / Mohan, Smriti / DeLaMora, Patricia A / Durrant, Karen L / Muskardin, Theresa Wampler / Correia Marques, Mariana / Onel, Karen B / Dedeoglu, Fatma / Gutierrez, Maria J / Schulert, Grant

    Frontiers in pediatrics

    2023  Volume 11, Page(s) 1323946

    Abstract: This corrects the article DOI: 10.3389/fped.2023.1240242.]. ...

    Abstract [This corrects the article DOI: 10.3389/fped.2023.1240242.].
    Language English
    Publishing date 2023-11-06
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2711999-3
    ISSN 2296-2360
    ISSN 2296-2360
    DOI 10.3389/fped.2023.1323946
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Anti-inflammatory therapy for COVID-19 infection: the case for colchicine.

    Reyes, Aaron Z / Hu, Kelly A / Teperman, Jacob / Wampler Muskardin, Theresa L / Tardif, Jean-Claude / Shah, Binita / Pillinger, Michael H

    Annals of the rheumatic diseases

    2020  Volume 80, Issue 5, Page(s) 550–557

    Abstract: The search for effective COVID-19 management strategies continues to evolve. Current understanding of SARS-CoV-2 mechanisms suggests a central role for exaggerated activation of the innate immune system as an important contributor to COVID-19 adverse ... ...

    Abstract The search for effective COVID-19 management strategies continues to evolve. Current understanding of SARS-CoV-2 mechanisms suggests a central role for exaggerated activation of the innate immune system as an important contributor to COVID-19 adverse outcomes. The actions of colchicine, one of the oldest anti-inflammatory therapeutics, target multiple mechanisms associated with COVID-19 excessive inflammation. While many COVID-19 trials have sought to manipulate SARS-CoV-2 or dampen the inflammatory response once patients are hospitalised, few examine therapeutics to prevent the need for hospitalisation. Colchicine is easily administered, generally well tolerated and inexpensive, and holds particular promise to reduce the risk of hospitalisation and mortality due to COVID-19 in the outpatient setting. Successful outpatient treatment of COVID-19 could greatly reduce morbidity, mortality and the demand for rare or expensive care resources (front-line healthcare workers, hospital beds, ventilators, biological therapies), to the benefit of both resource-replete and resource-poor regions.
    MeSH term(s) Anti-Inflammatory Agents/therapeutic use ; Colchicine/therapeutic use ; Humans ; SARS-CoV-2 ; COVID-19 Drug Treatment
    Chemical Substances Anti-Inflammatory Agents ; Colchicine (SML2Y3J35T)
    Language English
    Publishing date 2020-12-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/annrheumdis-2020-219174
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19.

    Nln, Ilona / Fernandez-Ruiz, Ruth / Muskardin, Theresa L Wampler / Paredes, Jacqueline L / Blazer, Ashira D / Tuminello, Stephanie / Attur, Mukundan / Iturrate, Eduardo / Petrilli, Christopher M / Abramson, Steven B / Chakravarti, Aravinda / Niewold, Timothy B

    Translational research : the journal of laboratory and clinical medicine

    2022  Volume 244, Page(s) 47–55

    Abstract: Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We ...

    Abstract Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (756 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR = 29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in antiviral immunity.
    MeSH term(s) Aged ; Alleles ; Antiviral Agents ; COVID-19/genetics ; Genetic Predisposition to Disease ; Humans ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/metabolism ; Interferon-alpha/genetics ; Lupus Erythematosus, Systemic/genetics ; Middle Aged ; Polymorphism, Single Nucleotide
    Chemical Substances Antiviral Agents ; Interferon Regulatory Factors ; Interferon-alpha
    Language English
    Publishing date 2022-01-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2246684-8
    ISSN 1878-1810 ; 1532-6543 ; 1931-5244
    ISSN (online) 1878-1810 ; 1532-6543
    ISSN 1931-5244
    DOI 10.1016/j.trsl.2022.01.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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