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  1. Article ; Online: Joint-specific memory, resident memory T cells and the rolling window of opportunity in arthritis.

    Chang, Margaret H / Fuhlbrigge, Robert C / Nigrovic, Peter A

    Nature reviews. Rheumatology

    2024  Volume 20, Issue 5, Page(s) 258–271

    Abstract: In rheumatoid arthritis, juvenile idiopathic arthritis and other forms of inflammatory arthritis, the immune system targets certain joints but not others. The pattern of joints affected varies by disease and by individual, with flares most commonly ... ...

    Abstract In rheumatoid arthritis, juvenile idiopathic arthritis and other forms of inflammatory arthritis, the immune system targets certain joints but not others. The pattern of joints affected varies by disease and by individual, with flares most commonly involving joints that were previously inflamed. This phenomenon, termed joint-specific memory, is difficult to explain by systemic immunity alone. Mechanisms of joint-specific memory include the involvement of synovial resident memory T cells that remain in the joint during remission and initiate localized disease recurrence. In addition, arthritis-induced durable changes in synovial fibroblasts and macrophages can amplify inflammation in a site-specific manner. Together with ongoing systemic processes that promote extension of arthritis to new joints, these local factors set the stage for a stepwise progression in disease severity, a paradigm for arthritis chronicity that we term the joint accumulation model. Although durable drug-free remission through early treatment remains elusive for most forms of arthritis, the joint accumulation paradigm defines new therapeutic targets, emphasizes the importance of sustained treatment to prevent disease extension to new joints, and identifies a rolling window of opportunity for altering the natural history of arthritis that extends well beyond the initiation phase of disease.
    MeSH term(s) Humans ; Memory T Cells/immunology ; Arthritis, Rheumatoid/immunology ; Joints/immunology ; Joints/pathology ; Immunologic Memory/immunology ; Disease Progression ; Animals ; Synovial Membrane/immunology ; Synovial Membrane/pathology ; Arthritis/immunology
    Language English
    Publishing date 2024-04-10
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2491532-4
    ISSN 1759-4804 ; 1759-4790
    ISSN (online) 1759-4804
    ISSN 1759-4790
    DOI 10.1038/s41584-024-01107-7
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  2. Article ; Online: COVID-19 cytokine storm: what is in a name?

    Nigrovic, Peter A

    Annals of the rheumatic diseases

    2020  Volume 80, Issue 1, Page(s) 3–5

    MeSH term(s) COVID-19 ; Cytokine Release Syndrome ; Cytokines ; Humans ; SARS-CoV-2
    Chemical Substances Cytokines
    Keywords covid19
    Language English
    Publishing date 2020-11-17
    Publishing country England
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/annrheumdis-2020-219448
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  3. Article ; Online: "Rounding Third Base and Heading Home": Arthritis & Rheumatology in 2024.

    Solomon, Daniel H / Kaplan, Mariana J / Nigrovic, Peter A / Bucala, Richard

    Arthritis & rheumatology (Hoboken, N.J.)

    2024  

    Language English
    Publishing date 2024-04-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.42828
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  4. Article ; Online: The Conundrum of Lung Disease and Drug Hypersensitivity-like Reactions in Systemic Juvenile Idiopathic Arthritis.

    Binstadt, Bryce A / Nigrovic, Peter A

    Arthritis & rheumatology (Hoboken, N.J.)

    2022  Volume 74, Issue 7, Page(s) 1122–1131

    Abstract: An unusual form of lung disease has begun to affect some children with systemic juvenile idiopathic arthritis (JIA), coincident with increasing utilization of interleukin-1 (IL-1) and IL-6 antagonists. Many children with systemic JIA-associated lung ... ...

    Abstract An unusual form of lung disease has begun to affect some children with systemic juvenile idiopathic arthritis (JIA), coincident with increasing utilization of interleukin-1 (IL-1) and IL-6 antagonists. Many children with systemic JIA-associated lung disease (SJIA-LD) have a history of clinical and laboratory features resembling drug reaction with eosinophilia and systemic symptoms (DRESS), a presentation now convincingly associated with HLA-DRB1*15. Treatment of DRESS typically requires drug discontinuation, a daunting prospect for clinicians and families who rely upon these agents. Here we review SJIA-LD and its associated DRESS-like phenotype. We suggest an alternative explanation, the cytokine plasticity hypothesis, proposing that IL-1 and IL-6 blockers modulate the milieu in which T cells develop, leading to a pathologic immune response triggered through exposure to common microbes, or to other exogenous or endogenous antigens, rather than to the drugs themselves. This hypothesis differs from DRESS in mechanism but also in clinical implications, predicting that control of pathogenic T cells could permit continued use of IL-1 and IL-6 antagonists in some individuals. The spectrum posed by these two hypotheses provides a conceptual framework that will guide investigation into the pathogenesis of SJIA-LD and may open up new therapeutic avenues for patients with systemic JIA.
    MeSH term(s) Arthritis, Juvenile/complications ; Arthritis, Juvenile/diagnosis ; Arthritis, Juvenile/drug therapy ; Drug Hypersensitivity/complications ; Humans ; Interleukin-1/antagonists & inhibitors ; Interleukin-6/antagonists & inhibitors ; Lung Diseases/complications
    Chemical Substances Interleukin-1 ; Interleukin-6
    Language English
    Publishing date 2022-05-29
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.42137
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  5. Article ; Online: Implications of Evolving Disease Classification for Drug Approval in Juvenile Idiopathic Arthritis.

    Case, Siobhan M / Nigrovic, Peter A

    Paediatric drugs

    2022  Volume 24, Issue 3, Page(s) 185–191

    Abstract: The classification of inflammatory arthritis incorporates a sharp divide between diseases of childhood onset, grouped together as juvenile idiopathic arthritis, and diseases such as rheumatoid arthritis that begin by definition in adulthood. An important ...

    Abstract The classification of inflammatory arthritis incorporates a sharp divide between diseases of childhood onset, grouped together as juvenile idiopathic arthritis, and diseases such as rheumatoid arthritis that begin by definition in adulthood. An important consequence of this divide is that regulatory authorities and many rheumatologists regard pediatric and adult arthritides as truly different, with the implication that drugs should be evaluated separately for each category. However, it is now clear that most forms of arthritis transcend the pediatric/adult boundary and that agents generally exhibit comparable success irrespective of age of onset, offering new opportunities in drug development and regulation focused on pharmacology and safety rather than efficacy. This paradigm shift will enable advances in arthritis treatment, originating either with adults or children, to translate more rapidly across the age spectrum.
    MeSH term(s) Adult ; Arthritis, Juvenile/drug therapy ; Child ; Drug Approval ; Humans
    Language English
    Publishing date 2022-04-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1492748-2
    ISSN 1179-2019 ; 1174-5878
    ISSN (online) 1179-2019
    ISSN 1174-5878
    DOI 10.1007/s40272-022-00496-0
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  6. Article ; Online: Storm Warning: Lung Disease in Systemic Juvenile Idiopathic Arthritis.

    Nigrovic, Peter A

    Arthritis & rheumatology (Hoboken, N.J.)

    2019  Volume 71, Issue 11, Page(s) 1773–1775

    MeSH term(s) Arthritis, Juvenile ; Humans ; Lung Diseases
    Language English
    Publishing date 2019-09-22
    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.41071
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  7. Article: Estrogen-Driven Changes in Immunoglobulin G Fc Glycosylation.

    Lagattuta, Kaitlyn A / Nigrovic, Peter A

    Experientia supplementum (2012)

    2021  Volume 112, Page(s) 341–361

    Abstract: Glycosylation within the immunoglobulin G (IgG) Fc region modulates its ability to engage complement and Fc receptors, affording the opportunity to fine-tune effector functions. Mechanisms regulating IgG Fc glycans remain poorly understood. Changes ... ...

    Abstract Glycosylation within the immunoglobulin G (IgG) Fc region modulates its ability to engage complement and Fc receptors, affording the opportunity to fine-tune effector functions. Mechanisms regulating IgG Fc glycans remain poorly understood. Changes accompanying menarche, menopause, and pregnancy have long implicated hormonal factors. Intervention studies now confirm that estrogens enhance IgG Fc galactosylation, in females and also in males, defining the first pathway modulating Fc glycans and thereby a new link between sex and immunity. This mechanism may participate in fetal-maternal immunity, antibody-mediated inflammation, and other aspects of age- and sex-specific immune function. Here we review the changes affecting the IgG Fc glycome from childhood through old age, the evidence establishing a role for estrogens, and research directions to uncover associated mechanisms that may inform therapeutic intervention.
    MeSH term(s) Estrogens ; Female ; Glycosylation ; Humans ; Immunoglobulin Fc Fragments/genetics ; Immunoglobulin Fc Fragments/metabolism ; Immunoglobulin G/metabolism ; Male ; Pregnancy ; Receptors, Fc/genetics ; Receptors, Fc/metabolism
    Chemical Substances Estrogens ; Immunoglobulin Fc Fragments ; Immunoglobulin G ; Receptors, Fc
    Language English
    Publishing date 2021-10-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 1664-431X
    ISSN 1664-431X
    DOI 10.1007/978-3-030-76912-3_11
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  8. Article ; Online: The 4th NextGen Therapies for SJIA and MAS: part 1 the elephant in the room: diagnostic/classification criteria for systemic juvenile idiopathic arthritis and adult-onset still's disease.

    Nigrovic, Peter A / de Benedetti, Fabrizio / Kimura, Yukiko / Lovell, Daniel J / Vastert, Sebastiaan J

    Pediatric rheumatology online journal

    2024  Volume 21, Issue Suppl 1, Page(s) 114

    Abstract: Currently, the criteria used to classify patients with SJIA are different from those used for AOSD. However, it has been recognized that the existing terms are too narrow, subdividing the Still's population unnecessarily between pediatric-onset and adult- ...

    Abstract Currently, the criteria used to classify patients with SJIA are different from those used for AOSD. However, it has been recognized that the existing terms are too narrow, subdividing the Still's population unnecessarily between pediatric-onset and adult-onset disease and excluding an appreciable group of children in whom overt arthritis is delayed or absent. Government regulators and insurers rely upon the guidance of subject experts to provide disease definitions, and when these definitions are flawed, to provide new and better ones. The classification session at the NextGen 2022 conference helped to serve this purpose, establishing the need for a revised definitional system that transcends the fault lines that remain in existing definitions.
    MeSH term(s) Adult ; Child ; Humans ; Arthritis, Juvenile/diagnosis ; Still's Disease, Adult-Onset/diagnosis
    Language English
    Publishing date 2024-01-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2279468-2
    ISSN 1546-0096 ; 1546-0096
    ISSN (online) 1546-0096
    ISSN 1546-0096
    DOI 10.1186/s12969-023-00864-1
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  9. Article ; Online: Recent advances and evolving concepts in Still's disease.

    Ruscitti, Piero / Cantarini, Luca / Nigrovic, Peter A / McGonagle, Dennis / Giacomelli, Roberto

    Nature reviews. Rheumatology

    2024  Volume 20, Issue 2, Page(s) 116–132

    Abstract: Still's disease is a rare inflammatory syndrome that encompasses systemic juvenile idiopathic arthritis and adult-onset Still's disease, both of which can exhibit life-threatening complications, including macrophage activation syndrome (MAS), a secondary ...

    Abstract Still's disease is a rare inflammatory syndrome that encompasses systemic juvenile idiopathic arthritis and adult-onset Still's disease, both of which can exhibit life-threatening complications, including macrophage activation syndrome (MAS), a secondary form of haemophagocytic lymphohistiocytosis. Genetic insights into Still's disease involve both HLA and non-HLA susceptibility genes, suggesting the involvement of adaptive immune cell-mediated immunity. At the same time, phenotypic evidence indicates the involvement of autoinflammatory processes. Evidence also implicates the type I interferon signature, mechanistic target of rapamycin complex 1 signalling and ferritin in the pathogenesis of Still's disease and MAS. Pathological entities associated with Still's disease include lung disease that could be associated with biologic DMARDs and with the occurrence of MAS. Historically, monophasic, recurrent and persistent Still's disease courses were recognized. Newer proposals of alternative Still's disease clusters could enable better dissection of clinical heterogeneity on the basis of immune cell profiles that could represent diverse endotypes or phases of disease activity. Therapeutically, data on IL-1 and IL-6 antagonism and Janus kinase inhibition suggest the importance of early administration in Still's disease. Furthermore, there is evidence that patients who develop MAS can be treated with IFNγ antagonism. Despite these developments, unmet needs remain that can form the basis for the design of future studies leading to improvement of disease management.
    MeSH term(s) Adult ; Humans ; Arthritis, Juvenile/drug therapy ; Antirheumatic Agents/therapeutic use ; Macrophage Activation Syndrome/drug therapy ; Macrophage Activation Syndrome/etiology ; Still's Disease, Adult-Onset/complications ; Still's Disease, Adult-Onset/drug therapy ; Lymphohistiocytosis, Hemophagocytic/drug therapy
    Chemical Substances Antirheumatic Agents
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2491532-4
    ISSN 1759-4804 ; 1759-4790
    ISSN (online) 1759-4804
    ISSN 1759-4790
    DOI 10.1038/s41584-023-01065-6
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  10. Article ; Online: Building an ARC to Grant Success: The Aims Review Committee.

    Nigrovic, Peter A

    Arthritis care & research

    2017  Volume 69, Issue 4, Page(s) 459–461

    MeSH term(s) Advisory Committees/standards ; Biomedical Research/economics ; Biomedical Research/methods ; Biomedical Research/standards ; Humans ; Peer Review, Research/methods ; Peer Review, Research/standards
    Language English
    Publishing date 2017-03-03
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 645059-3
    ISSN 2151-4658 ; 0893-7524 ; 2151-464X
    ISSN (online) 2151-4658
    ISSN 0893-7524 ; 2151-464X
    DOI 10.1002/acr.23087
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