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  1. Book ; Online: Type I Interferon in Human Autoimmunity

    Niewold, Timothy B.

    2015  

    Abstract: The type I interferon system plays a critical role in host defense in health, and a growing body of literature suggests that type I interferon is a critical mediator of human autoimmune disease. Type I interferons function as a bridge between the innate ... ...

    Abstract The type I interferon system plays a critical role in host defense in health, and a growing body of literature suggests that type I interferon is a critical mediator of human autoimmune disease. Type I interferons function as a bridge between the innate and adaptive immune systems, and as such play an important role in setting thresholds for response against self antigens. Many investigators have focused on the role type I interferons play in autoimmune disease. This fascinating and rapidly growing body of literature encompasses many different autoimmune diseases, including systemic lupus erythematosus, type I diabetes, multiple sclerosis, and others. In this Research Topic, we provide a comprehensive overview of the various roles type I interferons play in autoimmune diseases, with a focus on human immunology
    Keywords Immunologic diseases. Allergy ; Medicine (General)
    Size 1 electronic resource (87 p.)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT020090989
    ISBN 9782889193400 ; 2889193403
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Type I interferon.

    Niewold, Timothy B

    Cytokine

    2020  Volume 132, Page(s) 155109

    Keywords covid19
    Language English
    Publishing date 2020-04-22
    Publishing country England
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2020.155109
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Genetically transitional disease: conceptual understanding and applicability to rheumatic disease.

    Niewold, Timothy B / Aksentijevich, Ivona / Gorevic, Peter D / Gibson, Greg / Yao, Qingping

    Nature reviews. Rheumatology

    2024  Volume 20, Issue 5, Page(s) 301–310

    Abstract: In genomic medicine, the concept of genetically transitional disease (GTD) refers to cases in which gene mutation is necessary but not sufficient to cause disease. In this Perspective, we apply this novel concept to rheumatic diseases, which have been ... ...

    Abstract In genomic medicine, the concept of genetically transitional disease (GTD) refers to cases in which gene mutation is necessary but not sufficient to cause disease. In this Perspective, we apply this novel concept to rheumatic diseases, which have been linked to hundreds of genetic variants via association studies. These variants are in the 'grey zone' between monogenic variants with large effect sizes and common susceptibility alleles with small effect sizes. Among genes associated with rare autoinflammatory diseases, many low-frequency and/or low-penetrance variants are known to increase susceptibility to systemic inflammation. In autoimmune diseases, hundreds of HLA and non-HLA genetic variants have been revealed to be modest- to moderate-risk alleles. These diseases can be reclassified as GTDs. The same concept could apply to many other human diseases. GTD could improve the reporting of genetic testing results, diagnostic yields, genetic counselling and selection of therapy, as well as facilitating research using a novel approach to human genetic diseases.
    MeSH term(s) Humans ; Rheumatic Diseases/genetics ; Rheumatic Diseases/diagnosis ; Genetic Predisposition to Disease ; Mutation ; Genetic Variation ; Genetic Testing/methods
    Language English
    Publishing date 2024-02-28
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2491532-4
    ISSN 1759-4804 ; 1759-4790
    ISSN (online) 1759-4804
    ISSN 1759-4790
    DOI 10.1038/s41584-024-01086-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Is Rheumatoid Arthritis a Causal Factor in Cardiovascular Disease?

    Bridges, S Louis / Niewold, Timothy B / Merriman, Tony R

    Arthritis & rheumatology (Hoboken, N.J.)

    2022  Volume 74, Issue 10, Page(s) 1612–1614

    MeSH term(s) Arthritis, Rheumatoid/complications ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Causality ; Humans ; Risk Factors
    Language English
    Publishing date 2022-08-25
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.42236
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Advances in the management of systemic lupus erythematosus.

    Morand, Eric F / Fernandez-Ruiz, Ruth / Blazer, Ashira / Niewold, Timothy B

    BMJ (Clinical research ed.)

    2023  Volume 383, Page(s) e073980

    Abstract: Systemic lupus erythematosus (SLE) is a severe multisystem autoimmune disease that can cause injury in almost every body system. While considered a classic example of autoimmunity, it is still relatively poorly understood. Treatment with ... ...

    Abstract Systemic lupus erythematosus (SLE) is a severe multisystem autoimmune disease that can cause injury in almost every body system. While considered a classic example of autoimmunity, it is still relatively poorly understood. Treatment with immunosuppressive agents is challenging, as many agents are relatively non-specific, and the underlying disease is characterized by unpredictable flares and remissions. This State of The Art Review provides a comprehensive current summary of systemic lupus erythematosus based on recent literature. In basic and translational science, this summary includes the current state of genetics, epigenetics, differences by ancestry, and updates about the molecular and immunological pathogenesis of systemic lupus erythematosus. In clinical science, the summary includes updates in diagnosis and classification, clinical features and subphenotypes, and current guidelines and strategies for treatment. The paper also provides a comprehensive review of the large number of recent clinical trials in systemic lupus erythematosus. Current knowns and unknowns are presented, and potential directions for the future are suggested. Improved knowledge of immunological pathogenesis and the molecular differences that exist between patients should help to personalize treatment, minimize side effects, and achieve better outcomes in this difficult disease.
    MeSH term(s) Humans ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/drug therapy ; Immunosuppressive Agents/therapeutic use ; Autoimmunity
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2023-10-26
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1362901-3
    ISSN 1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    ISSN (online) 1756-1833
    ISSN 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    DOI 10.1136/bmj-2022-073980
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Type I Interferons in Autoimmunity.

    Fernandez-Ruiz, Ruth / Niewold, Timothy B

    The Journal of investigative dermatology

    2022  Volume 142, Issue 3 Pt B, Page(s) 793–803

    Abstract: Dysregulated IFN-1 responses play crucial roles in the development of multiple forms of autoimmunity. Many patients with lupus, systemic sclerosis, Sjogren's syndrome, and dermatomyositis demonstrate enhanced IFN-1 signaling. IFN-1 excess is associated ... ...

    Abstract Dysregulated IFN-1 responses play crucial roles in the development of multiple forms of autoimmunity. Many patients with lupus, systemic sclerosis, Sjogren's syndrome, and dermatomyositis demonstrate enhanced IFN-1 signaling. IFN-1 excess is associated with disease severity and autoantibodies and could potentially predict response to newer therapies targeting IFN-1 pathways. In this review, we provide an overview of the signaling pathway and immune functions of IFN-1s in health and disease. We also review the systemic autoimmune diseases classically associated with IFN-1 upregulation and current therapeutic strategies targeting the IFN-1 system.
    MeSH term(s) Autoimmunity ; Humans ; Interferon Type I/metabolism ; Lupus Erythematosus, Systemic ; Scleroderma, Systemic ; Signal Transduction ; Sjogren's Syndrome
    Chemical Substances Interferon Type I
    Language English
    Publishing date 2022-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2021.11.031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Connective tissue diseases: Targeting type I interferon in systemic lupus erythematosus.

    Niewold, Timothy B

    Nature reviews. Rheumatology

    2016  Volume 12, Issue 7, Page(s) 377–378

    Language English
    Publishing date 2016-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2491532-4
    ISSN 1759-4804 ; 1759-4790
    ISSN (online) 1759-4804
    ISSN 1759-4790
    DOI 10.1038/nrrheum.2016.83
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Type I interferon antagonists in clinical development for lupus.

    Paredes, Jacqueline L / Niewold, Timothy B

    Expert opinion on investigational drugs

    2020  Volume 29, Issue 9, Page(s) 1025–1041

    Abstract: Introduction: Systemic lupus erythematosus (SLE) is a severe chronic and incurable autoimmune disease. Treatment includes glucocorticoids and immunosuppressants which typically result in partial responses, and hence there is a great need for new ... ...

    Abstract Introduction: Systemic lupus erythematosus (SLE) is a severe chronic and incurable autoimmune disease. Treatment includes glucocorticoids and immunosuppressants which typically result in partial responses, and hence there is a great need for new therapies. The type I interferon (IFN) pathway is activated in more than 50% of SLE patients, and it is strongly implicated as a pathogenic factor in SLE.
    Areas covered: We searched the literature using 'SLE and interferon antagonists' as search terms. This identified a number of therapeutics that have entered clinical development targeting type I IFN in SLE. These include monoclonal antibodies against type I IFN cytokines and a kinoid vaccination strategy to induce anti-IFN antibodies.
    Expert opinion: Type I IFN antagonists have had some success, but many molecules have not progressed to phase III. These varied results are likely attributed to the multiple concurrent cytokine abnormalities present in SLE, the imprecise nature of the IFN signature as a readout for type I IFN and difficulties with clinical trials such as background medication use and diffuse composite disease activity measures. Despite these challenges, it seems likely that a type I IFN antagonist will come to clinical utility for SLE given the large unmet need and the recent phase III success with anifrolumab.
    MeSH term(s) Animals ; Antibodies, Monoclonal/pharmacology ; Cytokines/immunology ; Drug Development ; Humans ; Interferon Type I/antagonists & inhibitors ; Interferon Type I/immunology ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/physiopathology
    Chemical Substances Antibodies, Monoclonal ; Cytokines ; Interferon Type I
    Language English
    Publishing date 2020-09-01
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1182884-5
    ISSN 1744-7658 ; 0967-8298 ; 1354-3784
    ISSN (online) 1744-7658
    ISSN 0967-8298 ; 1354-3784
    DOI 10.1080/13543784.2020.1797677
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: T Cells in Systemic Lupus Erythematosus.

    Paredes, Jacqueline L / Fernandez-Ruiz, Ruth / Niewold, Timothy B

    Rheumatic diseases clinics of North America

    2021  Volume 47, Issue 3, Page(s) 379–393

    Abstract: T-cell dysregulation has been implicated in the loss of tolerance and overactivation of B ...

    Abstract T-cell dysregulation has been implicated in the loss of tolerance and overactivation of B cells in systemic lupus erythematosus (SLE). Recent studies have identified T-cell subsets and genetic, epigenetic, and environmental factors that contribute to pathogenic T-cell differentiation, as well as disease pathogenesis and clinical phenotypes in SLE. Many therapeutics targeting T-cell pathways are under development, and although many have not progressed in clinical trials, the recent approval of the calcineurin inhibitor voclosporin is encouraging. Further study of T-cell subsets and biomarkers of T-cell action may pave the way for specific targeting of pathogenic T-cell populations in SLE.
    MeSH term(s) B-Lymphocytes ; Humans ; Lupus Erythematosus, Systemic/drug therapy ; T-Lymphocytes
    Language English
    Publishing date 2021-06-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 92118-x
    ISSN 1558-3163 ; 0889-857X
    ISSN (online) 1558-3163
    ISSN 0889-857X
    DOI 10.1016/j.rdc.2021.04.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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