Robert T. Maughan, Erin MacDonald‐Dunlop, Lubna Haroon‐Rashid, Louise Sorensen, Natalie Chaddock, Shauna Masters, Andrew Porter, Marta Peverelli, Charis Pericleous, Andrew Hutchings, James Robinson, Taryn Youngstein, Raashid A. Luqmani, Justin C. Mason, Ann W. Morgan, James E. Peters
BackgroundTakayasu arteritis (TAK) and giant cell arteritis (GCA), the most common forms of large‐vessel vasculitis (LVV), can result in serious morbidity. Understanding the molecular basis of LVV should aid in developing better biomarkers and treatments.MethodsPlasma proteomic profiling of 184 proteins was performed in two cohorts. Cohort 1 included patients with established TAK (n=96) and large‐vessel GCA (LV‐GCA, n=35) in addition to healthy control participants (HCs, n=35). Cohort 2 comprised patients presenting acutely with possible cranial‐GCA in whom the diagnosis was subsequently confirmed (C‐GCA, n=150) or excluded (Not C‐GCA, n=89). Proteomic findings were compared to published transcriptomic data from LVV‐affected arteries.ResultsIn Cohort 1, comparison to HCs revealed 52 differentially abundant proteins (DAPs) in TAK and 72 in LV‐GCA. Within‐case analyses identified 16 and 18 disease activity‐associated proteins in TAK and LV‐GCA, respectively. In Cohort 2, comparing C‐GCA versus Not C‐GCA revealed 31 DAPs. Analysis within C‐GCA cases suggested the presence of distinct endotypes, with more pronounced proteomic changes in the biopsy‐proven subgroup. Cross‐comparison of TAK, LV‐GCA and biopsy‐proven C‐GCA revealed highly similar plasma proteomic profiles, with 26 shared DAPs including IL6, monocyte/macrophage related proteins (CCL7, CSF1), tissue remodelling proteins (TIMP1, TNC) and novel associations (TNFSF14, IL7R). Plasma proteomic findings reflected LVV arterial phenotype; for 42% of DAPs, the corresponding gene was differentially expressed in tissue.ConclusionsThese findings suggest shared pathobiology across the LVV spectrum involving innate immunity, lymphocyte homeostasis and tissue remodelling. Network‐based analyses highlighted immune‐stromal crosstalk and identified novel therapeutic targets (e.g. TNFSF14).
{"title":"Proteomic profiling of the large‐vessel vasculitis spectrum identifies shared signatures of innate immune activation and stromal remodelling","authors":"Robert T. Maughan, Erin MacDonald‐Dunlop, Lubna Haroon‐Rashid, Louise Sorensen, Natalie Chaddock, Shauna Masters, Andrew Porter, Marta Peverelli, Charis Pericleous, Andrew Hutchings, James Robinson, Taryn Youngstein, Raashid A. Luqmani, Justin C. Mason, Ann W. Morgan, James E. Peters","doi":"10.1002/art.43110","DOIUrl":"https://doi.org/10.1002/art.43110","url":null,"abstract":"BackgroundTakayasu arteritis (TAK) and giant cell arteritis (GCA), the most common forms of large‐vessel vasculitis (LVV), can result in serious morbidity. Understanding the molecular basis of LVV should aid in developing better biomarkers and treatments.MethodsPlasma proteomic profiling of 184 proteins was performed in two cohorts. Cohort 1 included patients with established TAK (n=96) and large‐vessel GCA (LV‐GCA, n=35) in addition to healthy control participants (HCs, n=35). Cohort 2 comprised patients presenting acutely with possible cranial‐GCA in whom the diagnosis was subsequently confirmed (C‐GCA, n=150) or excluded (Not C‐GCA, n=89). Proteomic findings were compared to published transcriptomic data from LVV‐affected arteries.ResultsIn Cohort 1, comparison to HCs revealed 52 differentially abundant proteins (DAPs) in TAK and 72 in LV‐GCA. Within‐case analyses identified 16 and 18 disease activity‐associated proteins in TAK and LV‐GCA, respectively. In Cohort 2, comparing C‐GCA versus Not C‐GCA revealed 31 DAPs. Analysis within C‐GCA cases suggested the presence of distinct endotypes, with more pronounced proteomic changes in the biopsy‐proven subgroup. Cross‐comparison of TAK, LV‐GCA and biopsy‐proven C‐GCA revealed highly similar plasma proteomic profiles, with 26 shared DAPs including IL6, monocyte/macrophage related proteins (CCL7, CSF1), tissue remodelling proteins (TIMP1, TNC) and novel associations (TNFSF14, IL7R). Plasma proteomic findings reflected LVV arterial phenotype; for 42% of DAPs, the corresponding gene was differentially expressed in tissue.ConclusionsThese findings suggest shared pathobiology across the LVV spectrum involving innate immunity, lymphocyte homeostasis and tissue remodelling. Network‐based analyses highlighted immune‐stromal crosstalk and identified novel therapeutic targets (e.g. TNFSF14).","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"22 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leonard H Calabrese, Michael Putman, Jeffrey A. Sparks, Zachary Wallace, Alfred H.J. Kim, Kevin L Winthrop, Cassandra Calabrese
{"title":"The National Academies’ 2024 Diagnostic Criteria for Long COVID: Concerns that Could Affect the Rheumatology Community","authors":"Leonard H Calabrese, Michael Putman, Jeffrey A. Sparks, Zachary Wallace, Alfred H.J. Kim, Kevin L Winthrop, Cassandra Calabrese","doi":"10.1002/art.43114","DOIUrl":"https://doi.org/10.1002/art.43114","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"42 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sindhu R Johnson, Marcy Bolster, Sonye K Danoff, Michael George, Gordon Guyatt, Dinesh Khanna, Reza Mirza, Aberdeen Allen, Amy Turner, Elana J. Bernstein
Click on the article title to read more.
{"title":"Reply, SARD-ILD Screening and Monitoring Recommendations with low certainty evidence","authors":"Sindhu R Johnson, Marcy Bolster, Sonye K Danoff, Michael George, Gordon Guyatt, Dinesh Khanna, Reza Mirza, Aberdeen Allen, Amy Turner, Elana J. Bernstein","doi":"10.1002/art.43111","DOIUrl":"https://doi.org/10.1002/art.43111","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"7 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xizhang Sun, Jaime L Chao, Michael Gerner, Keith B Elkon
Photosensitivity occurs in ~75% of lupus patients. Although ultraviolet light radiation (UVR) stimulates Type I interferon (IFN-I) in the skin, how UVR induced skin inflammation leads to downstream effects is poorly understood. Tissue inflammation causes DC to migrate from organs to draining lymph nodes (dLN) including a recently identified inflammatory DC subset (inf cDC2) that are potent antigen presenting cells. To explore links between UVR and the early immune response, we examined DC and lymphocyte subset migration to dLNs in normal and a lupus prone mouse strains as well as the role of IFN-I.
{"title":"UV Light Exposure Induces a Type I Interferon Dependent Activation and Migration of Inflammatory Dendritic Cells to Local Lymph Nodes","authors":"Xizhang Sun, Jaime L Chao, Michael Gerner, Keith B Elkon","doi":"10.1002/art.43108","DOIUrl":"https://doi.org/10.1002/art.43108","url":null,"abstract":"Photosensitivity occurs in ~75% of lupus patients. Although ultraviolet light radiation (UVR) stimulates Type I interferon (IFN-I) in the skin, how UVR induced skin inflammation leads to downstream effects is poorly understood. Tissue inflammation causes DC to migrate from organs to draining lymph nodes (dLN) including a recently identified inflammatory DC subset (inf cDC2) that are potent antigen presenting cells. To explore links between UVR and the early immune response, we examined DC and lymphocyte subset migration to dLNs in normal and a lupus prone mouse strains as well as the role of IFN-I.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"40 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vanessa L. Kronzer, Yangyuna Yang, Punyasha Roul, James L. Crooks, Cynthia S. Crowson, John M. Davis, Jeffrey A. Sparks, Jeffrey R. Pierce, Katelyn O'Dell, Brian C. Sauer, Grant W. Cannon, Joshua F. Baker, Ted R. Mikuls, Bryant R. England
Determine whether pollutants such as fire smoke-related particulate matter smaller than 2.5 microns (PM2.5) are associated with incident rheumatoid arthritis (RA) and RA-associated interstitial lung disease (RA-ILD).
{"title":"Associations of fire smoke and other pollutants with incident rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease","authors":"Vanessa L. Kronzer, Yangyuna Yang, Punyasha Roul, James L. Crooks, Cynthia S. Crowson, John M. Davis, Jeffrey A. Sparks, Jeffrey R. Pierce, Katelyn O'Dell, Brian C. Sauer, Grant W. Cannon, Joshua F. Baker, Ted R. Mikuls, Bryant R. England","doi":"10.1002/art.43113","DOIUrl":"https://doi.org/10.1002/art.43113","url":null,"abstract":"Determine whether pollutants such as fire smoke-related particulate matter smaller than 2.5 microns (PM<sub>2.5</sub>) are associated with incident rheumatoid arthritis (RA) and RA-associated interstitial lung disease (RA-ILD).","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"172 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angela Y.Y. Tam, Korsa Khan, Shiwen Xu, Marianne Bergin, Linghong Huang, Erik Arroyo Colon, Danyi Cheng, Elisabetta AM Verderio, Voon Ong, Christopher P Denton, John Atkinson, Tim S Johnson, David J. Abraham
Scleroderma is a life-threatening autoimmune disease characterized by inflammation, tissue remodelling, and fibrosis. This study aimed to investigate the expression and function of transglutaminase 2 (TGM2) in scleroderma skin and experimentally-induced dermal fibrosis to determine its potential role and therapeutic implications.
{"title":"Critical role for Transglutaminase 2 in scleroderma skin fibrosis and in the development of dermal sclerosis in a mouse model of scleroderma","authors":"Angela Y.Y. Tam, Korsa Khan, Shiwen Xu, Marianne Bergin, Linghong Huang, Erik Arroyo Colon, Danyi Cheng, Elisabetta AM Verderio, Voon Ong, Christopher P Denton, John Atkinson, Tim S Johnson, David J. Abraham","doi":"10.1002/art.43104","DOIUrl":"https://doi.org/10.1002/art.43104","url":null,"abstract":"Scleroderma is a life-threatening autoimmune disease characterized by inflammation, tissue remodelling, and fibrosis. This study aimed to investigate the expression and function of transglutaminase 2 (TGM2) in scleroderma skin and experimentally-induced dermal fibrosis to determine its potential role and therapeutic implications.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"27 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rheumatoid arthritis (RA) is a life-long autoimmune disease caused by the confluence of genetic and environmental variables that lead to loss of self-tolerance and persistent joint inflammation. RA occurs at the highest incidence in individuals >65 years old, implicating the aging process in disease susceptibility. Transformative approaches in molecular immunology and in functional genomics have paved the way for pathway paradigms underlying the replacement of immune homeostasis with auto-destructive immunity in affected patients, including the process of immune aging. Patients with RA have a signature of premature immune aging, best understood for CD4+ T cells which function as pathogenic effectors in this HLA class II-associated disease. Premature immune aging is present in healthy HLA-DRB1*04+ individuals, placing accelerated immune aging prior to joint inflammation. Aging-related molecular abnormalities directly implicated in turning RA CD4+ T cells into pro-inflammatory effector cells are linked to malfunction of subcellular organelles, such as mitochondria, lysosomes, lipid droplets and the endoplasmic reticulum. Resulting changes in T cell behavior include cellular hypermobility; tissue invasiveness; unopposed mTORC activation; excessive release of tumor necrosis factor α (TNF); lysosomal failure; clonal expansion and immunogenic cell death. Aged and metabolically reprogrammed T cells in RA patients are accompanied by age-associated B cells (ABC), which specialize in autoantibody production. Clonal hematopoiesis drives myeloid cell aging by producing aged monocytes and hypermetabolic macrophages (Mϕ) that sustain the process of inflammaging. Here, we synthesize insights into the relationship of RA risk and immune aging and discuss mechanisms through which immune aging can cause autoimmunity.
{"title":"Immune Aging in Rheumatoid Arthritis","authors":"Cornelia M. Weyand, Jörg J. Goronzy","doi":"10.1002/art.43105","DOIUrl":"https://doi.org/10.1002/art.43105","url":null,"abstract":"Rheumatoid arthritis (RA) is a life-long autoimmune disease caused by the confluence of genetic and environmental variables that lead to loss of self-tolerance and persistent joint inflammation. RA occurs at the highest incidence in individuals >65 years old, implicating the aging process in disease susceptibility. Transformative approaches in molecular immunology and in functional genomics have paved the way for pathway paradigms underlying the replacement of immune homeostasis with auto-destructive immunity in affected patients, including the process of immune aging. Patients with RA have a signature of premature immune aging, best understood for CD4<sup>+</sup> T cells which function as pathogenic effectors in this HLA class II-associated disease. Premature immune aging is present in healthy HLA-DRB1*04<sup>+</sup> individuals, placing accelerated immune aging prior to joint inflammation. Aging-related molecular abnormalities directly implicated in turning RA CD4<sup>+</sup> T cells into pro-inflammatory effector cells are linked to malfunction of subcellular organelles, such as mitochondria, lysosomes, lipid droplets and the endoplasmic reticulum. Resulting changes in T cell behavior include cellular hypermobility; tissue invasiveness; unopposed mTORC activation; excessive release of tumor necrosis factor α (TNF); lysosomal failure; clonal expansion and immunogenic cell death. Aged and metabolically reprogrammed T cells in RA patients are accompanied by age-associated B cells (ABC), which specialize in autoantibody production. Clonal hematopoiesis drives myeloid cell aging by producing aged monocytes and hypermetabolic macrophages (Mϕ) that sustain the process of inflammaging. Here, we synthesize insights into the relationship of RA risk and immune aging and discuss mechanisms through which immune aging can cause autoimmunity.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"29 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Air Pollution's Hidden Toll: Risks for Rheumatoid Arthritis and RA-Associated Lung Disease","authors":"S. Ajeganova, J. Sokolove","doi":"10.1002/art.43115","DOIUrl":"https://doi.org/10.1002/art.43115","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"21 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on: 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases","authors":"Julian Segan, Michael Putman, Richard Conway","doi":"10.1002/art.43106","DOIUrl":"https://doi.org/10.1002/art.43106","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"37 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reply to: Limitations in the Real‐World Emulation of the HORIZON Pivotal Fracture Trial","authors":"Elvira D'Andrea, Shirley Wang","doi":"10.1002/art.43103","DOIUrl":"https://doi.org/10.1002/art.43103","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"101 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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