Sara Faghihi-Kashani, Akira Yoshida, Francisca Bozan, Giovanni Zanframundo, Davide Rozza, Aravinthan Loganathan, Eduardo Dourado, Gianluca Sambataro, Iazsmin Bauer Ventura, Sangmee Sharon Bae, Darosa Lim, Daphne Rivero Gallegos, Yasuhiko Yamano, Albert Selva-O'Callaghan, Andrew L. Mammen, Carlo A. Scirè, Carlomaurizio Montecucco, Chester V. Oddis, David Fiorentino, Francesco Bonella, Frederick W. Miller, Ingrid E. Lundberg, Jens Schmidt, Jorge Rojas-Serrano, Marie Hudson, Masataka Kuwana, Miguel Angel González-Gay, Neil McHugh, Tamera J. Corte, Tracy Jennifer Doyle, Victoria P. Werth, Latika Gupta, Diana Isabel Perez Roman, Lorenzo M. Bianchessi, Phani Kumar Devarasetti, Samuel Katsuyuki Shinjo, Fabrizio Luppi, Ilaria Cavazzana, Siamak Moghadam-Kia, Marco Fornaro, Elizabeth R. Volkmann, Matteo Piga, Jesus Loarce-Martos, Giacomo De Luca, Johannes Knitza, Veronica Wolff-Cecchi, Marco Sebastiani, Adam Schiffenbauer, Lisa G. Rider, Raquel Campanilho-Marques, Lucian Marts, Elena Bravi, Harsha Gunawardena, , Rohit Aggarwal, Lorenzo Cavagna
Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD.
{"title":"Clinical Characteristics of Anti-Synthetase Syndrome: Analysis from the CLASS project","authors":"Sara Faghihi-Kashani, Akira Yoshida, Francisca Bozan, Giovanni Zanframundo, Davide Rozza, Aravinthan Loganathan, Eduardo Dourado, Gianluca Sambataro, Iazsmin Bauer Ventura, Sangmee Sharon Bae, Darosa Lim, Daphne Rivero Gallegos, Yasuhiko Yamano, Albert Selva-O'Callaghan, Andrew L. Mammen, Carlo A. Scirè, Carlomaurizio Montecucco, Chester V. Oddis, David Fiorentino, Francesco Bonella, Frederick W. Miller, Ingrid E. Lundberg, Jens Schmidt, Jorge Rojas-Serrano, Marie Hudson, Masataka Kuwana, Miguel Angel González-Gay, Neil McHugh, Tamera J. Corte, Tracy Jennifer Doyle, Victoria P. Werth, Latika Gupta, Diana Isabel Perez Roman, Lorenzo M. Bianchessi, Phani Kumar Devarasetti, Samuel Katsuyuki Shinjo, Fabrizio Luppi, Ilaria Cavazzana, Siamak Moghadam-Kia, Marco Fornaro, Elizabeth R. Volkmann, Matteo Piga, Jesus Loarce-Martos, Giacomo De Luca, Johannes Knitza, Veronica Wolff-Cecchi, Marco Sebastiani, Adam Schiffenbauer, Lisa G. Rider, Raquel Campanilho-Marques, Lucian Marts, Elena Bravi, Harsha Gunawardena, , Rohit Aggarwal, Lorenzo Cavagna","doi":"10.1002/art.43038","DOIUrl":"https://doi.org/10.1002/art.43038","url":null,"abstract":"Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"4 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519702","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.","authors":"Bryant R England, Rebecca T Brooks, Ted R Mikuls","doi":"10.1002/art.43048","DOIUrl":"10.1002/art.43048","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491470","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}
Priyanka Yalamanchili, Lydia Y Lee, Greta Bushnell, Melissa L Mannion, Chintan V Dave, Daniel B Horton
Objective: To describe recent trends in DMARD use for children with juvenile idiopathic arthritis (JIA) in the US.
Methods: We used commercial claims data (2000-2022) to perform a serial cross-sectional utilization study of children ages 1-18 diagnosed with JIA. Initiations of conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs were identified after a ≥12-month baseline and expressed as percentage of all new DMARD initiations per year, by category, class, and individual agent. Trends were evaluated using linear regression. Secondarily, we examined first b/tsDMARDs initiated after csDMARD monotherapy.
Results: We identified 20,258 new DMARD use episodes among 13,696 individuals (median age 14 years, 67.5% female). csDMARDs, while most commonly used overall, declined from 89.5% of new use episodes to 43.2% (2001-2022, p<0.001 for trend). In contrast, bDMARD use increased (10.5-50.0%, p<0.001). For tumor necrosis factor inhibitors (TNFi), etanercept peaked at 28.3% (2006) and declined to 4.2% (2022) (p=0.002). Meanwhile, adalimumab use doubled (7.0-14.0%, 2007-2008) after JIA approval, increasing further following a less painful formulation release (20.5%, 2022, p<0.001). However, overall TNFi use has declined with increasing use of other b/tsDMARDs, particularly ustekinumab, secukinumab, and tofacitinib. By 2022, adalimumab was the most common b/tsDMARD initiated first after csDMARDs (77.8%).
Conclusion: Among commercially insured children with JIA in the US, new b/tsDMARD use is rising while new csDMARD use declines. For b/tsDMARDs, adalimumab is most used and the predominant b/tsDMARD initiated first after csDMARDs. Patterns in DMARD use for JIA have evolved relative to multiple factors, including regulatory approvals and tolerability.
{"title":"Trends in New Use of Disease-Modifying Antirheumatic Drugs in Juvenile Idiopathic Arthritis Among Commercially Insured Children in the United States from 2001-2022.","authors":"Priyanka Yalamanchili, Lydia Y Lee, Greta Bushnell, Melissa L Mannion, Chintan V Dave, Daniel B Horton","doi":"10.1002/art.43041","DOIUrl":"10.1002/art.43041","url":null,"abstract":"<p><strong>Objective: </strong>To describe recent trends in DMARD use for children with juvenile idiopathic arthritis (JIA) in the US.</p><p><strong>Methods: </strong>We used commercial claims data (2000-2022) to perform a serial cross-sectional utilization study of children ages 1-18 diagnosed with JIA. Initiations of conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs were identified after a ≥12-month baseline and expressed as percentage of all new DMARD initiations per year, by category, class, and individual agent. Trends were evaluated using linear regression. Secondarily, we examined first b/tsDMARDs initiated after csDMARD monotherapy.</p><p><strong>Results: </strong>We identified 20,258 new DMARD use episodes among 13,696 individuals (median age 14 years, 67.5% female). csDMARDs, while most commonly used overall, declined from 89.5% of new use episodes to 43.2% (2001-2022, p<0.001 for trend). In contrast, bDMARD use increased (10.5-50.0%, p<0.001). For tumor necrosis factor inhibitors (TNFi), etanercept peaked at 28.3% (2006) and declined to 4.2% (2022) (p=0.002). Meanwhile, adalimumab use doubled (7.0-14.0%, 2007-2008) after JIA approval, increasing further following a less painful formulation release (20.5%, 2022, p<0.001). However, overall TNFi use has declined with increasing use of other b/tsDMARDs, particularly ustekinumab, secukinumab, and tofacitinib. By 2022, adalimumab was the most common b/tsDMARD initiated first after csDMARDs (77.8%).</p><p><strong>Conclusion: </strong>Among commercially insured children with JIA in the US, new b/tsDMARD use is rising while new csDMARD use declines. For b/tsDMARDs, adalimumab is most used and the predominant b/tsDMARD initiated first after csDMARDs. Patterns in DMARD use for JIA have evolved relative to multiple factors, including regulatory approvals and tolerability.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453973","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}
Jie Wei, Yilun Wang, Chao Zeng, Guanghua Lei, Yuqing Zhang
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{"title":"Reply to insights into “Weight loss after initiating anti-obesity medications and gout among overweight and obesity individuals”","authors":"Jie Wei, Yilun Wang, Chao Zeng, Guanghua Lei, Yuqing Zhang","doi":"10.1002/art.43043","DOIUrl":"https://doi.org/10.1002/art.43043","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"12 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451923","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}
Sigrid V. Hestetun, Hamid K. Rudsari, Piotr Jaholkowski, Alexey Shadrin, Kristine L. Haftorn, Svend Andersen, Marite Rygg, Ellen Nordal, Oleksandr Frei, Ole A. Andreassen, Anne M. Selvaag, Ketil Størdal, Helga Sanner
We aimed to investigate the incidence of juvenile idiopathic arthritis (JIA) in the three geographical regions of Norway, and whether potential regional incidence differences are explained by environmental or genetic factors across regions.
{"title":"Incidence and genetic risk of juvenile idiopathic arthritis in Norway by latitude","authors":"Sigrid V. Hestetun, Hamid K. Rudsari, Piotr Jaholkowski, Alexey Shadrin, Kristine L. Haftorn, Svend Andersen, Marite Rygg, Ellen Nordal, Oleksandr Frei, Ole A. Andreassen, Anne M. Selvaag, Ketil Størdal, Helga Sanner","doi":"10.1002/art.43040","DOIUrl":"https://doi.org/10.1002/art.43040","url":null,"abstract":"We aimed to investigate the incidence of juvenile idiopathic arthritis (JIA) in the three geographical regions of Norway, and whether potential regional incidence differences are explained by environmental or genetic factors across regions.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"40 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451924","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}
Kevin Sheng-Kai Ma, Jui-En Lo, Vasileios C. Kyttaris, George C. Tsokos, Karen H. Costenbader
Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose co-transporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D).
{"title":"Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events and Safety Outcomes in Patients with Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-based Target Trial Emulation","authors":"Kevin Sheng-Kai Ma, Jui-En Lo, Vasileios C. Kyttaris, George C. Tsokos, Karen H. Costenbader","doi":"10.1002/art.43037","DOIUrl":"https://doi.org/10.1002/art.43037","url":null,"abstract":"Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose co-transporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D).","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451935","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}
Sara Bindoli, Stefania Vio, Marta Sbaraglia, Fabrizio Vianello, Roberta Ramonda
We are describing an unusual presentation of Erdheim-Chester Disease (ECD), a non -Langerhans histiocytosis provoked by abnormal aggregation of foamy histiocytes in several organs and systems. Our patient, already with osteoporosis, presented severe bilateral ankle pain with functional impairment, clinically mimicking “Complex Regional Pain Syndrome” (CRPS); the radiological images and subsequently the bone biopsy were fundamental for achieving the proper diagnosis. The diagnosis was challenging given the isolated bone localization which is uncommonly seen in ECD.
{"title":"A rare and misleading condition: isolated skeletal involvement of Erdheim-Chester Disease","authors":"Sara Bindoli, Stefania Vio, Marta Sbaraglia, Fabrizio Vianello, Roberta Ramonda","doi":"10.1002/art.43039","DOIUrl":"https://doi.org/10.1002/art.43039","url":null,"abstract":"We are describing an unusual presentation of Erdheim-Chester Disease (ECD), a non -Langerhans histiocytosis provoked by abnormal aggregation of foamy histiocytes in several organs and systems. Our patient, already with osteoporosis, presented severe bilateral ankle pain with functional impairment, clinically mimicking “Complex Regional Pain Syndrome” (CRPS); the radiological images and subsequently the bone biopsy were fundamental for achieving the proper diagnosis. The diagnosis was challenging given the isolated bone localization which is uncommonly seen in ECD.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"32 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451920","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}
Runa Kuley, Bhargavi Duvvuri, Sabeeha Hasnain, Ernst R. Dow, Alisa E. Koch, Richard E. Higgs, Venkatesh Krishnan, Christian Lood
Neutrophils play an important role in regulating immune and inflammatory responses in rheumatoid arthritis (RA). We assessed whether baricitinib, a JAK1/JAK2 inhibitor, could reduce neutrophil activation, and whether a neutrophil activation score could predict treatment response.
{"title":"Neutrophil activation markers can predict rheumatoid arthritis treatment response to the Janus Kinase 1/2 inhibitor baricitinib","authors":"Runa Kuley, Bhargavi Duvvuri, Sabeeha Hasnain, Ernst R. Dow, Alisa E. Koch, Richard E. Higgs, Venkatesh Krishnan, Christian Lood","doi":"10.1002/art.43042","DOIUrl":"https://doi.org/10.1002/art.43042","url":null,"abstract":"Neutrophils play an important role in regulating immune and inflammatory responses in rheumatoid arthritis (RA). We assessed whether baricitinib, a JAK1/JAK2 inhibitor, could reduce neutrophil activation, and whether a neutrophil activation score could predict treatment response.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451921","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}
Joshua F. Baker, George Reed, Ted R. Mikuls, Geoffrey M. Thiele, Dimitrios A. Pappas, Christina Charles‐Schoeman, Monica Guma, Leslie R. Harrold, Jeffrey R. Curtis, Joel M. Kremer
PurposeWe determined if metabolic syndrome, its components, and adipokines (adiponectin, leptin, Fibroblast Growth Factor‐21) were associated with response to advanced therapies among patients with rheumatoid arthritis (RA).MethodsThis study included participants with RA initiating either TNFi or non‐TNFi biologic therapies from the Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) cohort within the CorEvitas registry. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III definition. Adipokines were assessed on stored samples from a sub‐sample of responders and non‐responders (N=200). The primary outcome was the achievement of a change as large as the minimal clinically important difference (MCID) for the Clinical Disease Activity Index (CDAI) at 6 months.ResultsAmong 2,368 participants, 687 (29%) had metabolic syndrome. Metabolic syndrome was associated with lower odds of achieving CDAI MCID [OR (95% CI): 0.69 (0.56,0.86) p=0.001] with a dose‐dependent decrease in response rate according to the number of components present. Model fit was superior for metabolic syndrome compared to BMI. Associations between metabolic syndrome and MCID achievement were similar between patients receiving TNFi [OR (95% CI): 0.65 (0.49,0.87) p=0.003] v. non‐TNF therapies [OR (95% CI): 0.76 (0.55,1.04) p=0.08)] (p‐for‐interaction=0.49). Adipokines were not associated with MCID achievement.ConclusionsMetabolic syndrome is associated with lower response rates with the initiation of an advanced therapy in RA, with similar effects for both TNFi and non‐TNFi agents. Adipokines were strongly associated with metabolic syndrome but were not associated with clinical response.
{"title":"Metabolic Syndrome, Adipokines, and Response to Advanced Therapies in Rheumatoid Arthritis","authors":"Joshua F. Baker, George Reed, Ted R. Mikuls, Geoffrey M. Thiele, Dimitrios A. Pappas, Christina Charles‐Schoeman, Monica Guma, Leslie R. Harrold, Jeffrey R. Curtis, Joel M. Kremer","doi":"10.1002/art.43034","DOIUrl":"https://doi.org/10.1002/art.43034","url":null,"abstract":"PurposeWe determined if metabolic syndrome, its components, and adipokines (adiponectin, leptin, Fibroblast Growth Factor‐21) were associated with response to advanced therapies among patients with rheumatoid arthritis (RA).MethodsThis study included participants with RA initiating either TNFi or non‐TNFi biologic therapies from the <jats:italic>C</jats:italic>omparative <jats:italic>E</jats:italic>ffectiveness <jats:italic>R</jats:italic>egistry to study <jats:italic>T</jats:italic>herapies for <jats:italic>A</jats:italic>rthritis and <jats:italic>I</jats:italic>nflammatory Co<jats:italic>n</jats:italic>ditions (CERTAIN) cohort within the CorEvitas registry. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III definition. Adipokines were assessed on stored samples from a sub‐sample of responders and non‐responders (N=200). The primary outcome was the achievement of a change as large as the minimal clinically important difference (MCID) for the Clinical Disease Activity Index (CDAI) at 6 months.ResultsAmong 2,368 participants, 687 (29%) had metabolic syndrome. Metabolic syndrome was associated with lower odds of achieving CDAI MCID [OR (95% CI): 0.69 (0.56,0.86) p=0.001] with a dose‐dependent decrease in response rate according to the number of components present. Model fit was superior for metabolic syndrome compared to BMI. Associations between metabolic syndrome and MCID achievement were similar between patients receiving TNFi [OR (95% CI): 0.65 (0.49,0.87) p=0.003] v. non‐TNF therapies [OR (95% CI): 0.76 (0.55,1.04) p=0.08)] (p‐for‐interaction=0.49). Adipokines were not associated with MCID achievement.ConclusionsMetabolic syndrome is associated with lower response rates with the initiation of an advanced therapy in RA, with similar effects for both TNFi and non‐TNFi agents. Adipokines were strongly associated with metabolic syndrome but were not associated with clinical response.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"23 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448663","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}
Veerle F. A. M. Derksen, Klara Martinsson, Anouk G. van Mourik, Carlijn A. Wagenaar, René E. M. Toes, Wendy Walrabenstein, Daniel Sjöberg, Dirkjan van Schaardenburg, Tom W. J. Huizinga, Alf Kastbom, Anna Svärd, Diane van der Woude
ObjectiveAnti‐citrullinated protein antibodies (ACPA) have been detected in sputum and saliva, indicating that anti‐modified protein antibodies (AMPA) can be produced at mucosal sites in rheumatoid arthritis (RA) patients. However, the body's largest mucosal compartment, the gut, has not yet been examined. We therefore investigated the presence of several AMPA (antibodies against citrullinated (ACPA), carbamylated (anti‐CarP) and acetylated (AAPA) proteins) at different mucosal sites, including the intestinal tract.MethodsPaired fecal/ileal wash, saliva and serum samples of RA patients and healthy volunteers were collected in two independent cohorts. Data involving feces was replicated in a third cohort. In these secretions AMPA were analyzed using in‐house ELISA with unmodified peptides as control. In fecal samples total IgA and anti‐E. coli IgA were measured.ResultsACPA, anti‐CarP and AAPA IgA were measurable in saliva of seropositive RA patients (prevalence 9‐40%). No AMPA could be detected in feces. IgA was present since total IgA and anti‐E. coli IgA was detectable in feces of ACPA‐positive RA patients and healthy donors. Results were confirmed in another cohort using colonoscopically collected ileal wash samples.ConclusionOur study shows the presence of ACPA, anti‐CarP and AAPA IgA in saliva of ACPA‐seropositive RA patients. However, no AMPA could be detected in feces/ileal wash samples of these patients, although our assays were able to measure other antigen‐specific antibodies. These data suggest that mucosal autoantibody secretion may occur in the oral mucosa of RA patients, while no evidence could be found for this process in the lower gastro‐intestinal tract.
目的在痰液和唾液中检测到抗瓜氨酸蛋白抗体（ACPA），表明类风湿性关节炎（RA）患者的粘膜部位可能产生抗修饰蛋白抗体（AMPA）。然而，对人体最大的粘膜区--肠道--尚未进行研究。因此，我们研究了包括肠道在内的不同粘膜部位是否存在几种 AMPA（针对瓜氨酸化蛋白（ACPA）、氨甲酰化蛋白（抗 CarP）和乙酰化蛋白（AAPA）的抗体）。涉及粪便的数据在第三个队列中进行了重复。采用内部 ELISA 法分析这些分泌物中的 AMPA，并以未修饰的肽作为对照。在粪便样本中检测了总 IgA 和抗大肠杆菌 IgA。结果 在血清阳性 RA 患者的唾液中可检测到 AMPA、抗 CARP 和 AAPA IgA（发病率为 9-40%）。粪便中检测不到 AMPA。ACPA阳性RA患者和健康供体的粪便中可检测到总IgA和抗大肠杆菌IgA，因此存在IgA。结论：我们的研究表明，ACPA 血清阳性 RA 患者的唾液中存在 ACPA、抗 CarP 和 AAPA IgA。然而，在这些患者的粪便/回肠洗液样本中检测不到 AMPA，尽管我们的检测方法能够检测到其他抗原特异性抗体。这些数据表明，RA 患者的口腔黏膜可能会分泌黏膜自身抗体，而在下胃肠道却找不到这一过程的证据。
{"title":"Anti‐modified protein antibodies can be detected in saliva, but not in intestinal secretions of seropositive rheumatoid arthritis patients – evidence of site‐specific mucosal autoantibody secretion in RA","authors":"Veerle F. A. M. Derksen, Klara Martinsson, Anouk G. van Mourik, Carlijn A. Wagenaar, René E. M. Toes, Wendy Walrabenstein, Daniel Sjöberg, Dirkjan van Schaardenburg, Tom W. J. Huizinga, Alf Kastbom, Anna Svärd, Diane van der Woude","doi":"10.1002/art.43036","DOIUrl":"https://doi.org/10.1002/art.43036","url":null,"abstract":"ObjectiveAnti‐citrullinated protein antibodies (ACPA) have been detected in sputum and saliva, indicating that anti‐modified protein antibodies (AMPA) can be produced at mucosal sites in rheumatoid arthritis (RA) patients. However, the body's largest mucosal compartment, the gut, has not yet been examined. We therefore investigated the presence of several AMPA (antibodies against citrullinated (ACPA), carbamylated (anti‐CarP) and acetylated (AAPA) proteins) at different mucosal sites, including the intestinal tract.MethodsPaired fecal/ileal wash, saliva and serum samples of RA patients and healthy volunteers were collected in two independent cohorts. Data involving feces was replicated in a third cohort. In these secretions AMPA were analyzed using in‐house ELISA with unmodified peptides as control. In fecal samples total IgA and anti‐E. coli IgA were measured.ResultsACPA, anti‐CarP and AAPA IgA were measurable in saliva of seropositive RA patients (prevalence 9‐40%). No AMPA could be detected in feces. IgA was present since total IgA and anti‐E. coli IgA was detectable in feces of ACPA‐positive RA patients and healthy donors. Results were confirmed in another cohort using colonoscopically collected ileal wash samples.ConclusionOur study shows the presence of ACPA, anti‐CarP and AAPA IgA in saliva of ACPA‐seropositive RA patients. However, no AMPA could be detected in feces/ileal wash samples of these patients, although our assays were able to measure other antigen‐specific antibodies. These data suggest that mucosal autoantibody secretion may occur in the oral mucosa of RA patients, while no evidence could be found for this process in the lower gastro‐intestinal tract.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"7 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448671","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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