Pub Date : 2024-07-30DOI: 10.1186/s13075-024-03372-z
L Andrés Cerezo, A Navrátilová, M Kuklová, A Prokopcová, J Baloun, T Kropáčková, D Veigl, S Popelka, P Fulín, R Ballay, K Pavelka, J Vencovský, L Šenolt
Introduction: IL-40 is a novel cytokine associated with autoimmune connective tissue disorders such as rheumatoid arthritis (RA) or Sjögren syndrome. We have previously shown an accumulation of IL-40 in the RA joint and its expression by immune cells and fibroblasts. Therefore, we aimed to assess the role of IL-40 in association with hyaline cartilage and chondrocyte activity.
Methods: Immunohistochemistry was employed to detect IL-40 in paired samples of loaded and unloaded regions of osteoarthritis (OA) cartilage (n=5). Synovial fluid IL-40 was analysed by ELISA in OA (n=31) and control individuals after knee injury (n=34). The impact of IL-40 on chondrocytes was tested in vitro.
Results: IL-40 was found in chondrocytes of the superficial zone of the OA cartilage, both in loaded and unloaded explants. Additionally, only biopsies from loaded explants showed significant IL-40 positivity in transitional zone chondrocytes. Levels of IL-40 were significantly elevated in the synovial fluid from OA patients compared to controls (p<0.0009) and correlated with synovial fluid leukocyte counts in OA (r=0.444, p=0.014). Chondrocytes exposed to IL-40 dose dependently increased in the secretion of pro-inflammatory cytokines IL-6 (p<0.0001) and IL-8 (p=0.004). Moreover, a dose dependent up-regulation of matrix degrading metalloproteinases MMP-1 (p=0.004), MMP-3 (p=0.031) and MMP-13 (p=0.0002) upon IL-40 treatment was observed in contrast to untreated chondrocytes.
Conclusion: This study is the first to demonstrate the accumulation of IL-40 in OA cartilage and its up-regulation in the synovial fluid of OA patients compared to controls. In addition, extracellular IL-40 appears to play a role in promoting inflammation and cartilage destruction by driving chondrocyte behaviour towards a more aggressive phenotype.
{"title":"IL-40 is up-regulated in the synovial fluid and cartilage of osteoarthritis patients and contributes to the alteration of chondrocytes phenotype in vitro.","authors":"L Andrés Cerezo, A Navrátilová, M Kuklová, A Prokopcová, J Baloun, T Kropáčková, D Veigl, S Popelka, P Fulín, R Ballay, K Pavelka, J Vencovský, L Šenolt","doi":"10.1186/s13075-024-03372-z","DOIUrl":"10.1186/s13075-024-03372-z","url":null,"abstract":"<p><strong>Introduction: </strong>IL-40 is a novel cytokine associated with autoimmune connective tissue disorders such as rheumatoid arthritis (RA) or Sjögren syndrome. We have previously shown an accumulation of IL-40 in the RA joint and its expression by immune cells and fibroblasts. Therefore, we aimed to assess the role of IL-40 in association with hyaline cartilage and chondrocyte activity.</p><p><strong>Methods: </strong>Immunohistochemistry was employed to detect IL-40 in paired samples of loaded and unloaded regions of osteoarthritis (OA) cartilage (n=5). Synovial fluid IL-40 was analysed by ELISA in OA (n=31) and control individuals after knee injury (n=34). The impact of IL-40 on chondrocytes was tested in vitro.</p><p><strong>Results: </strong>IL-40 was found in chondrocytes of the superficial zone of the OA cartilage, both in loaded and unloaded explants. Additionally, only biopsies from loaded explants showed significant IL-40 positivity in transitional zone chondrocytes. Levels of IL-40 were significantly elevated in the synovial fluid from OA patients compared to controls (p<0.0009) and correlated with synovial fluid leukocyte counts in OA (r=0.444, p=0.014). Chondrocytes exposed to IL-40 dose dependently increased in the secretion of pro-inflammatory cytokines IL-6 (p<0.0001) and IL-8 (p=0.004). Moreover, a dose dependent up-regulation of matrix degrading metalloproteinases MMP-1 (p=0.004), MMP-3 (p=0.031) and MMP-13 (p=0.0002) upon IL-40 treatment was observed in contrast to untreated chondrocytes.</p><p><strong>Conclusion: </strong>This study is the first to demonstrate the accumulation of IL-40 in OA cartilage and its up-regulation in the synovial fluid of OA patients compared to controls. In addition, extracellular IL-40 appears to play a role in promoting inflammation and cartilage destruction by driving chondrocyte behaviour towards a more aggressive phenotype.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"146"},"PeriodicalIF":4.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-30DOI: 10.1186/s13075-024-03367-w
Kwanghoon Lee, Marina Banuls-Mirete, Alecio F. Lombardi, Alexander I.B. Posis, Eric Y. Chang, Nancy E. Lane, Monica Guma
Adipose tissue has been associated with knee osteoarthritis (KOA) pathogenesis, but the longitudinal changes in adipose tissue with KOA progression have not been carefully evaluated. This study aimed to determine if longitudinal changes of systemic and local adipose tissue is associated with radiographic progression of KOA. This case-control study used data from the Osteoarthritis Initiative (OAI) and included 315 cases (all the right knees with a minimum of Kellgren-Lawrence score (KL) of 0 and an increase of ≥ 1 KL from baseline to 48 months) and 315 controls matched by age, sex, race, and baseline KL. Cross sectional area of IPFP (IPFP CSA) and subcutaneous adipose tissue around the distal thigh (SCATthigh) were measured using MRI images at baseline and 24 months. Conditional logistic regression models were fitted to estimate associations of obesity markers, IPFP CSA, and SCATthigh with radiographic KOA progression. Mediation analysis was used to assess whether IPFP CSA or SCATthigh mediates the relationships between baseline BMI and radiographic KOA progression. 24-month changes of IPFP CSA (ΔIPFP CSA) and SCATthigh (ΔSCATthigh) were significantly greater in cases compared to controls, whereas Δ BMI and Δ abdominal circumference were similar in both groups during follow-up. Adjusted ORs for radiographic KOA progression were 9.299, 95% CI (5.357–16.141) per 1 SD increase of Δ IPFP CSA and 1.646, 95% CI (1.288–2.103) per 1 SD increase of Δ SCATthigh. ΔIPFP CSA mediated the association between baseline BMI and radiographic KOA progression (87%). Subjects with radiographic progression of KOA, had significant increases in IPFP CSA and subcutaneous adipose tissue while BMI and abdominal circumference remained stable. Additional studies are needed to confirm these associations.
{"title":"Infrapatellar fat pad size and subcutaneous fat in knee osteoarthritis radiographic progression: data from the osteoarthritis initiative","authors":"Kwanghoon Lee, Marina Banuls-Mirete, Alecio F. Lombardi, Alexander I.B. Posis, Eric Y. Chang, Nancy E. Lane, Monica Guma","doi":"10.1186/s13075-024-03367-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03367-w","url":null,"abstract":"Adipose tissue has been associated with knee osteoarthritis (KOA) pathogenesis, but the longitudinal changes in adipose tissue with KOA progression have not been carefully evaluated. This study aimed to determine if longitudinal changes of systemic and local adipose tissue is associated with radiographic progression of KOA. This case-control study used data from the Osteoarthritis Initiative (OAI) and included 315 cases (all the right knees with a minimum of Kellgren-Lawrence score (KL) of 0 and an increase of ≥ 1 KL from baseline to 48 months) and 315 controls matched by age, sex, race, and baseline KL. Cross sectional area of IPFP (IPFP CSA) and subcutaneous adipose tissue around the distal thigh (SCATthigh) were measured using MRI images at baseline and 24 months. Conditional logistic regression models were fitted to estimate associations of obesity markers, IPFP CSA, and SCATthigh with radiographic KOA progression. Mediation analysis was used to assess whether IPFP CSA or SCATthigh mediates the relationships between baseline BMI and radiographic KOA progression. 24-month changes of IPFP CSA (ΔIPFP CSA) and SCATthigh (ΔSCATthigh) were significantly greater in cases compared to controls, whereas Δ BMI and Δ abdominal circumference were similar in both groups during follow-up. Adjusted ORs for radiographic KOA progression were 9.299, 95% CI (5.357–16.141) per 1 SD increase of Δ IPFP CSA and 1.646, 95% CI (1.288–2.103) per 1 SD increase of Δ SCATthigh. ΔIPFP CSA mediated the association between baseline BMI and radiographic KOA progression (87%). Subjects with radiographic progression of KOA, had significant increases in IPFP CSA and subcutaneous adipose tissue while BMI and abdominal circumference remained stable. Additional studies are needed to confirm these associations.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"183 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1186/s13075-024-03358-x
Ronald van Vollenhoven, Vibeke Strand, Tsutomu Takeuchi, Nilmo Chávez, Pablo Mannucci Walter, Atul Singhal, Jerzy Swierkot, Nasser Khan, Xianwei Bu, Yihan Li, Sara K. Penn, Heidi S. Camp, Jacob Aelion
To evaluate the efficacy and safety of upadacitinib monotherapy versus methotrexate (MTX) monotherapy over 5 years among MTX-naïve patients with moderately to severely active rheumatoid arthritis (RA) in the long-term extension (LTE) of the phase 3 SELECT-EARLY trial. Patients were randomized to receive upadacitinib 15 mg or 30 mg or MTX. Patients who did not achieve CDAI remission and had < 20% improvement in tender and swollen joint counts at week 26 received rescue therapy (addition of MTX in the upadacitinib group and addition of upadacitinib in the MTX group). Efficacy assessments were evaluated over 5 years and are reported as observed (AO) for patients who received continuous monotherapy with upadacitinib 15/30 mg or MTX and by randomized group applying non-responder imputation (NRI). Treatment-emergent adverse events (TEAEs) per 100 patient-years were summarized over 5 years. Of 945 patients randomized and treated, 775 (82%) completed week 48 and entered the LTE on study drug. Higher proportions of patients consistently achieved disease activity targets over 5 years with upadacitinib than MTX. In AO analyses, 53%/59% of patients attained CDAI remission with upadacitinib 15/30 mg versus 43% with MTX at week 260. NRI analyses showed better CDAI, DAS28(CRP), and ACR responses with upadacitinib relative to MTX at week 260 (all comparisons, nominal P < .001). Upadacitinib treatment also resulted in numerically greater inhibition of structural joint progression through week 260 compared to MTX. Most TEAEs, serious AEs, and AEs leading to discontinuation were numerically higher in patients receiving upadacitinib 30 mg. Rates of serious infections, herpes zoster, creatine phosphokinase elevation, nonmelanoma skin cancer, and neutropenia were numerically higher with upadacitinib than MTX. The observed safety profile of upadacitinib over 5 years was consistent with earlier trial results and integrated phase 3 safety analyses. Upadacitinib showed better clinical responses versus MTX in patients with RA throughout the 5-year trial. Higher rates of several AEs were observed with upadacitinib, especially in the 30 mg group, compared to MTX. When used as monotherapy in MTX-naïve patients, the approved upadacitinib 15 mg dose showed better long-term efficacy versus MTX and an overall favorable benefit-risk profile. NCT02706873.
{"title":"Upadacitinib monotherapy versus methotrexate monotherapy in patients with rheumatoid arthritis: efficacy and safety through 5 years in the SELECT-EARLY randomized controlled trial","authors":"Ronald van Vollenhoven, Vibeke Strand, Tsutomu Takeuchi, Nilmo Chávez, Pablo Mannucci Walter, Atul Singhal, Jerzy Swierkot, Nasser Khan, Xianwei Bu, Yihan Li, Sara K. Penn, Heidi S. Camp, Jacob Aelion","doi":"10.1186/s13075-024-03358-x","DOIUrl":"https://doi.org/10.1186/s13075-024-03358-x","url":null,"abstract":"To evaluate the efficacy and safety of upadacitinib monotherapy versus methotrexate (MTX) monotherapy over 5 years among MTX-naïve patients with moderately to severely active rheumatoid arthritis (RA) in the long-term extension (LTE) of the phase 3 SELECT-EARLY trial. Patients were randomized to receive upadacitinib 15 mg or 30 mg or MTX. Patients who did not achieve CDAI remission and had < 20% improvement in tender and swollen joint counts at week 26 received rescue therapy (addition of MTX in the upadacitinib group and addition of upadacitinib in the MTX group). Efficacy assessments were evaluated over 5 years and are reported as observed (AO) for patients who received continuous monotherapy with upadacitinib 15/30 mg or MTX and by randomized group applying non-responder imputation (NRI). Treatment-emergent adverse events (TEAEs) per 100 patient-years were summarized over 5 years. Of 945 patients randomized and treated, 775 (82%) completed week 48 and entered the LTE on study drug. Higher proportions of patients consistently achieved disease activity targets over 5 years with upadacitinib than MTX. In AO analyses, 53%/59% of patients attained CDAI remission with upadacitinib 15/30 mg versus 43% with MTX at week 260. NRI analyses showed better CDAI, DAS28(CRP), and ACR responses with upadacitinib relative to MTX at week 260 (all comparisons, nominal P < .001). Upadacitinib treatment also resulted in numerically greater inhibition of structural joint progression through week 260 compared to MTX. Most TEAEs, serious AEs, and AEs leading to discontinuation were numerically higher in patients receiving upadacitinib 30 mg. Rates of serious infections, herpes zoster, creatine phosphokinase elevation, nonmelanoma skin cancer, and neutropenia were numerically higher with upadacitinib than MTX. The observed safety profile of upadacitinib over 5 years was consistent with earlier trial results and integrated phase 3 safety analyses. Upadacitinib showed better clinical responses versus MTX in patients with RA throughout the 5-year trial. Higher rates of several AEs were observed with upadacitinib, especially in the 30 mg group, compared to MTX. When used as monotherapy in MTX-naïve patients, the approved upadacitinib 15 mg dose showed better long-term efficacy versus MTX and an overall favorable benefit-risk profile. NCT02706873.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"2 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1186/s13075-024-03371-0
Tobias Hoffmann, Ulf Teichgräber, Martin Förster, Peter Oelzner, Claus Kroegel, Diane Renz, Tobias Weise, Joachim Böttcher, P. Christian Schulze, Gunter Wolf, Marcus Franz, Alexander Pfeil
Inflammatory rheumatic diseases (IRD) are often associated with interstitial lung disease (ILD). The aim of the present study was to establish a correlation between the findings on HRCT and the immunological bronchoalveolar lavage (BAL). The study included 74 patients with newly diagnosed IRD and evidence of ILD on HRCT with the following pattern: ground-glass opacities (GGO), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Patients with other HRCT pattern were excluded. No patient received any immunosuppressive therapy. In addition to HRCT, immunological BAL was performed and the American Thoracic Society clinical practice guideline were used to define BAL patterns (lymphocytic cellular pattern, neutrophilic cellular pattern, eosinophilic cellular pattern and unspecified pattern). The main HRCT patterns were NSIP (47.3%), GGO (33.8%), and UIP (18.9%). BAL patterns showed the following distribution: 41.9% lymphocytic cellular pattern, 23.0% neutrophilic cellular pattern, 18.9% eosinophilic cellular pattern, and 16.2% unspecific cellular pattern. Placing these data in the context of the HRCT findings, the lymphocytic cellular BAL pattern (48%) was most commonly BAL pattern associated with GGO pattern in HRCT, whereas neutrophilic and lymphocytic cellular BAL patterns were the dominant feature in NSIP and UIP. In patients with new-onset IRD and ILD, inflammatory pulmonary changes are predominate, reflected by GGO on HRCT and a mainly lymphocytic cell profile in the immunological BAL. In NSIP or UIP on HRCT, the percentages of lymphocytes and neutrophils were higher in BAL fluid, representing a fibrotic component in addition to the inflammation. Consequently, patients with evidence of GGO on HRCT should primarily be treated with anti-inflammatory/immunosuppressive therapy, whereas in patients with NSIP and UIP a combination of anti-inflammatory and anti-fibrotic agents would be the appropriate treatment.
{"title":"Correlation of high-resolution computed tomography and immunological bronchoalveolar lavage in interstitial lung disease at the onset of inflammatory rheumatic diseases: implications for diagnosis and therapeutic strategies","authors":"Tobias Hoffmann, Ulf Teichgräber, Martin Förster, Peter Oelzner, Claus Kroegel, Diane Renz, Tobias Weise, Joachim Böttcher, P. Christian Schulze, Gunter Wolf, Marcus Franz, Alexander Pfeil","doi":"10.1186/s13075-024-03371-0","DOIUrl":"https://doi.org/10.1186/s13075-024-03371-0","url":null,"abstract":"Inflammatory rheumatic diseases (IRD) are often associated with interstitial lung disease (ILD). The aim of the present study was to establish a correlation between the findings on HRCT and the immunological bronchoalveolar lavage (BAL). The study included 74 patients with newly diagnosed IRD and evidence of ILD on HRCT with the following pattern: ground-glass opacities (GGO), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Patients with other HRCT pattern were excluded. No patient received any immunosuppressive therapy. In addition to HRCT, immunological BAL was performed and the American Thoracic Society clinical practice guideline were used to define BAL patterns (lymphocytic cellular pattern, neutrophilic cellular pattern, eosinophilic cellular pattern and unspecified pattern). The main HRCT patterns were NSIP (47.3%), GGO (33.8%), and UIP (18.9%). BAL patterns showed the following distribution: 41.9% lymphocytic cellular pattern, 23.0% neutrophilic cellular pattern, 18.9% eosinophilic cellular pattern, and 16.2% unspecific cellular pattern. Placing these data in the context of the HRCT findings, the lymphocytic cellular BAL pattern (48%) was most commonly BAL pattern associated with GGO pattern in HRCT, whereas neutrophilic and lymphocytic cellular BAL patterns were the dominant feature in NSIP and UIP. In patients with new-onset IRD and ILD, inflammatory pulmonary changes are predominate, reflected by GGO on HRCT and a mainly lymphocytic cell profile in the immunological BAL. In NSIP or UIP on HRCT, the percentages of lymphocytes and neutrophils were higher in BAL fluid, representing a fibrotic component in addition to the inflammation. Consequently, patients with evidence of GGO on HRCT should primarily be treated with anti-inflammatory/immunosuppressive therapy, whereas in patients with NSIP and UIP a combination of anti-inflammatory and anti-fibrotic agents would be the appropriate treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"2 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Rheumatoid arthritis (RA) patients sometimes exhibit different levels of improvement in health assessment questionnaire-disability index (HAQ-DI) and subjective pain visual analogue score (VAS) even after achieving low disease activities (LDA). This study aimed to identify factors associated with improvement in HAQ-DI and pain VAS among those who achieved LDA.
Methods: Data of the FIRST registry, a multi-institutional cohort of RA patients treated with biological and targeted-synthetic DMARDs (b/tsDMARDs) were analyzed. Patients who were enrolled from August 2013 to February 2023 and who achieved clinical LDA [clinical disease activity index (CDAI) ≤ 10.0] at 6 months after starting treatment were included. Multiple logistic regression analyses were conducted to identify the factors that associated with achieving HAQ-DI normalization (< 0.5), HAQ-DI improvement (by > 0.22), or pain VAS reduction (≤ 40 mm).
Results: Among 1424 patients who achieved LDA at 6 months, 732 patients achieved HAQ-DI normalization and 454 achieved pain VAS reduction. The seropositivity and the use of JAK inhibitor compared with TNF inhibitor were associated with both HAQ-DI < 0.5 and pain VAS reduction at 6 months. On the other hand, older age, past failure in ≥ 2 classes of b/tsDMARDs, higher HAQ-DI at baseline, and use of glucocorticoid were associated with the lower likelihood of HAQ-DI normalization and pain VAS reduction. Longer disease duration, being female, and higher disease activity at baseline was negatively associated HAQ-DI normalization alone. Comorbidities were not associated with the outcomes.
Conclusions: These results suggest some preferable treatment may exist for improvement of HAQ-DI and pain VAS reduction in the early stage of the treatment, which is a clue to prevention of a criteria of difficult-to-treat RA.
背景：类风湿关节炎（RA）患者即使在达到低疾病活动度（LDA）后，有时也会在健康评估问卷-残疾指数（HAQ-DI）和主观疼痛视觉模拟评分（VAS）方面表现出不同程度的改善。本研究旨在确定实现 LDA 的患者中 HAQ-DI 和疼痛 VAS 改善的相关因素：研究分析了FIRST登记处的数据，这是一个接受生物和靶向合成DMARDs（b/tsDMARDs）治疗的RA患者的多机构队列。研究纳入了 2013 年 8 月至 2023 年 2 月期间入组的患者，这些患者在开始治疗 6 个月后达到了临床 LDA [临床疾病活动指数 (CDAI) ≤ 10.0]。进行多元逻辑回归分析，以确定与实现 HAQ-DI 正常化（0.22）或疼痛 VAS 减轻（≤ 40 mm）相关的因素：结果：1424名患者在6个月后接受了LDA治疗，其中732名患者的HAQ-DI恢复正常，454名患者的疼痛VAS减轻。与 TNF 抑制剂相比，血清阳性和使用 JAK 抑制剂与 HAQ-DI 均有关联：这些结果表明，在治疗的早期阶段，可能存在一些改善 HAQ-DI 和减轻疼痛 VAS 的优选治疗方法，这是预防难以治疗的 RA 标准的线索。
{"title":"Predictors of functional improvement and pain reduction in rheumatoid arthritis patients who achieved low disease activity with disease-modifying antirheumatic drugs: a retrospective study of the FIRST Registry.","authors":"Sae Ochi, Koshiro Sonomoto, Shingo Nakayamada, Yoshiya Tanaka","doi":"10.1186/s13075-024-03369-8","DOIUrl":"10.1186/s13075-024-03369-8","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) patients sometimes exhibit different levels of improvement in health assessment questionnaire-disability index (HAQ-DI) and subjective pain visual analogue score (VAS) even after achieving low disease activities (LDA). This study aimed to identify factors associated with improvement in HAQ-DI and pain VAS among those who achieved LDA.</p><p><strong>Methods: </strong>Data of the FIRST registry, a multi-institutional cohort of RA patients treated with biological and targeted-synthetic DMARDs (b/tsDMARDs) were analyzed. Patients who were enrolled from August 2013 to February 2023 and who achieved clinical LDA [clinical disease activity index (CDAI) ≤ 10.0] at 6 months after starting treatment were included. Multiple logistic regression analyses were conducted to identify the factors that associated with achieving HAQ-DI normalization (< 0.5), HAQ-DI improvement (by > 0.22), or pain VAS reduction (≤ 40 mm).</p><p><strong>Results: </strong>Among 1424 patients who achieved LDA at 6 months, 732 patients achieved HAQ-DI normalization and 454 achieved pain VAS reduction. The seropositivity and the use of JAK inhibitor compared with TNF inhibitor were associated with both HAQ-DI < 0.5 and pain VAS reduction at 6 months. On the other hand, older age, past failure in ≥ 2 classes of b/tsDMARDs, higher HAQ-DI at baseline, and use of glucocorticoid were associated with the lower likelihood of HAQ-DI normalization and pain VAS reduction. Longer disease duration, being female, and higher disease activity at baseline was negatively associated HAQ-DI normalization alone. Comorbidities were not associated with the outcomes.</p><p><strong>Conclusions: </strong>These results suggest some preferable treatment may exist for improvement of HAQ-DI and pain VAS reduction in the early stage of the treatment, which is a clue to prevention of a criteria of difficult-to-treat RA.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"140"},"PeriodicalIF":4.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-26DOI: 10.1186/s13075-024-03365-y
Styliani Tsiami, Piet Dukatz, Maria Gkelaki, Philipp Sewerin, Uta Kiltz, Xenofon Baraliakos
Background: In spondyloarthritides (SpA) and fibromyalgia (FM), patients suffer from generalized pain. The impact of FM on PRO validated in SpA has not been systematically studied.
Objective: Study the performance of PROs developed for SpA in patients with primary (p) FM without chronic inflammatory-rheumatic disease vs. SpA without and with concomitant (c) FM.
Methods: Patients with pFM, axSpA or PsA and indication for treatment adaptation were prospectively included. Standardized PROs were assessed: BASDAI, ASDAS-CRP, DAPSA, patient´s global assessment, BASFI, LEI, MASES, SPARCC Enthesitis Score and FIQ.
Results: 300 patients were included (100/diagnosis). More males were found in axSpA vs. PsA and pFM group (67, 33 and 2/100, respectively), while 12 axSpA (axSpA+) and 16 PsA (PsA+) patients had cFM. pFM patients showed significantly higher scores in all assessments vs. axSpA or PsA, with exception of ASDAS-CRP (3.3 ± 0.6 in FM vs. 3.1 ± 1.0 in axSpA) and duration of low lumbar morning stiffness. Similar results were also found in the subanalysis of female patients only. In addition, patients with axSpA + or PsA + showed no differences to patients with pFM, while significantly higher scores were found for FM, axSpA + and PsA + for almost all FIQ items compared to axSpA- or PsA-.
Conclusions: PROs originally developed for axSpA or PsA need to be interpreted differently in the presence or absence of cFM. ASDAS-CRP and duration of lumbar morning stiffness were not affected by cFM. FM-specific questionnaires also showed high scores in patients with SpA with cFM but not in those without.
{"title":"Performance of standardized patient reported outcomes developed for spondyloarthritis in primary and concomitant forms of fibromyalgia.","authors":"Styliani Tsiami, Piet Dukatz, Maria Gkelaki, Philipp Sewerin, Uta Kiltz, Xenofon Baraliakos","doi":"10.1186/s13075-024-03365-y","DOIUrl":"10.1186/s13075-024-03365-y","url":null,"abstract":"<p><strong>Background: </strong>In spondyloarthritides (SpA) and fibromyalgia (FM), patients suffer from generalized pain. The impact of FM on PRO validated in SpA has not been systematically studied.</p><p><strong>Objective: </strong>Study the performance of PROs developed for SpA in patients with primary (p) FM without chronic inflammatory-rheumatic disease vs. SpA without and with concomitant (c) FM.</p><p><strong>Methods: </strong>Patients with pFM, axSpA or PsA and indication for treatment adaptation were prospectively included. Standardized PROs were assessed: BASDAI, ASDAS-CRP, DAPSA, patient´s global assessment, BASFI, LEI, MASES, SPARCC Enthesitis Score and FIQ.</p><p><strong>Results: </strong>300 patients were included (100/diagnosis). More males were found in axSpA vs. PsA and pFM group (67, 33 and 2/100, respectively), while 12 axSpA (axSpA+) and 16 PsA (PsA+) patients had cFM. pFM patients showed significantly higher scores in all assessments vs. axSpA or PsA, with exception of ASDAS-CRP (3.3 ± 0.6 in FM vs. 3.1 ± 1.0 in axSpA) and duration of low lumbar morning stiffness. Similar results were also found in the subanalysis of female patients only. In addition, patients with axSpA + or PsA + showed no differences to patients with pFM, while significantly higher scores were found for FM, axSpA + and PsA + for almost all FIQ items compared to axSpA- or PsA-.</p><p><strong>Conclusions: </strong>PROs originally developed for axSpA or PsA need to be interpreted differently in the presence or absence of cFM. ASDAS-CRP and duration of lumbar morning stiffness were not affected by cFM. FM-specific questionnaires also showed high scores in patients with SpA with cFM but not in those without.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"141"},"PeriodicalIF":4.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-25DOI: 10.1186/s13075-024-03377-8
David Kiefer, Mina Soltani, Parham Damirchi, Uta Kiltz, Bjoern Buehring, Ioana Andreica, Philipp Sewerin, Xenofon Baraliakos
Define the prevalence and location of inflammatory and structural lesions on magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and radiographic axial spondyloarthritis (r-axSpA) with neck pain as leading clinical symptom. Patients with diagnosis of RA and r-axSpA were consecutively included if they had chronic (> 3 months) neck pain. Clinical assessment, neck pain questionnaires and MRIs of the cervical spine (CS) were performed. 107 patients (59 RA and 48 r-axSpA) were included. While there was no difference in the Northwick-Park-Neck-Pain-questionnaire, patients with RA reported higher neck pain compared to r-axSpA on a numeric rating scale (5.0 ± 3.6 vs. 3.0 ± 3.1; p = 0.003). Inflammatory lesions occurred predominantly in the craniocervical area in RA and in the lower CS segments in r-axSpA. Bone marrow edema (BME) was more frequent in axSpA (BME-score axSpA/RA: 0.35vs0.17; p < 0.001) while synovitis was visible in both but was more prevalent in RA (synovitis-score axSpA/RA: 0.02vs0.1; p < 0.001). BME was found in 8 (13.6%) vertebral corner vs. 9 (18.8%), in 2 (3.4%) facet joints vs. 7 (14.6%) and in 1 (1.7%) spinous processes vs. 9 (18.8%) in patients with RA/r-axSpA. In contrast, more patients with RA (30.5% vs6.3%) showed erosive osteochondrosis with endplate BME (p = 0.002). While involvement of upper cervical inflammation was typically present in RA, r-axSpA patients showed more BME in lower CS segments, vertebral corners, facet joints and spinous processes. Neck pain is linked to upper and lower inflammatory and structural lesions of the CS in both diseases.
{"title":"Prevalence and location of inflammatory and structural lesions in patients with rheumatoid arthritis and radiographic axial spondyloarthritis with chronic neck pain evaluated by magnetic resonance imaging","authors":"David Kiefer, Mina Soltani, Parham Damirchi, Uta Kiltz, Bjoern Buehring, Ioana Andreica, Philipp Sewerin, Xenofon Baraliakos","doi":"10.1186/s13075-024-03377-8","DOIUrl":"https://doi.org/10.1186/s13075-024-03377-8","url":null,"abstract":"Define the prevalence and location of inflammatory and structural lesions on magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and radiographic axial spondyloarthritis (r-axSpA) with neck pain as leading clinical symptom. Patients with diagnosis of RA and r-axSpA were consecutively included if they had chronic (> 3 months) neck pain. Clinical assessment, neck pain questionnaires and MRIs of the cervical spine (CS) were performed. 107 patients (59 RA and 48 r-axSpA) were included. While there was no difference in the Northwick-Park-Neck-Pain-questionnaire, patients with RA reported higher neck pain compared to r-axSpA on a numeric rating scale (5.0 ± 3.6 vs. 3.0 ± 3.1; p = 0.003). Inflammatory lesions occurred predominantly in the craniocervical area in RA and in the lower CS segments in r-axSpA. Bone marrow edema (BME) was more frequent in axSpA (BME-score axSpA/RA: 0.35vs0.17; p < 0.001) while synovitis was visible in both but was more prevalent in RA (synovitis-score axSpA/RA: 0.02vs0.1; p < 0.001). BME was found in 8 (13.6%) vertebral corner vs. 9 (18.8%), in 2 (3.4%) facet joints vs. 7 (14.6%) and in 1 (1.7%) spinous processes vs. 9 (18.8%) in patients with RA/r-axSpA. In contrast, more patients with RA (30.5% vs6.3%) showed erosive osteochondrosis with endplate BME (p = 0.002). While involvement of upper cervical inflammation was typically present in RA, r-axSpA patients showed more BME in lower CS segments, vertebral corners, facet joints and spinous processes. Neck pain is linked to upper and lower inflammatory and structural lesions of the CS in both diseases.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"39 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-25DOI: 10.1186/s13075-024-03379-6
Neda Kortam, Wenying Liang, Claire Shiple, Suiyuan Huang, Rosemary Gedert, James St. Clair, Cyrus Sarosh, Caroline Foster, Pei-Suen Tsou, John Varga, Jason S. Knight, Dinesh Khanna, Ramadan A. Ali
Neutrophils and neutrophil extracellular traps (NETs) contribute to the vascular complications of multiple diseases, but their role in systemic sclerosis (SSc) is understudied. We sought to test the hypothesis that NETs are implicated in SSc vasculopathy and that treatment with prostacyclin analogs may ameliorate SSc vasculopathy not only through vasodilation but also by inhibiting NET release. Blood from 125 patients with SSc (87 diffuse cutaneous SSc and 38 limited cutaneous SSc) was collected at a single academic medical center. Vascular complications such as digital ulcers, pulmonary artery hypertension, and scleroderma renal crisis were recorded. The association between circulating NETs and vascular complications was determined using in vitro and ex vivo assays. The impact of the synthetic prostacyclin analog epoprostenol on NET release was determined. Neutrophil activation and NET release were elevated in patients with SSc-associated vascular complications compared to matched patients without vascular complications. Neutrophil activation and NETs positively correlated with soluble E-selectin and VCAM-1, circulating markers of vascular injury. Treatment of patients with digital ischemia with a synthetic prostacyclin analog boosted neutrophil cyclic AMP, which was associated with the blunting of NET release and reduced NETs in circulation. Our study demonstrates an association between NETs and vascular complications in SSc. We also identified the potential for an additional therapeutic benefit of synthetic prostacyclin analogs, namely to reduce neutrophil hyperactivity and NET release in SSc patients.
中性粒细胞和中性粒细胞胞外捕获物（NETs）会导致多种疾病的血管并发症，但它们在系统性硬化症（SSc）中的作用却未得到充分研究。我们试图验证这样一个假设：NET 与 SSc 血管病变有关，使用前列环素类似物治疗不仅可以通过扩张血管，还可以通过抑制 NET 释放来改善 SSc 血管病变。研究人员在一家学术医疗中心采集了 125 名 SSc 患者（87 名弥漫性皮肤 SSc 患者和 38 名局限性皮肤 SSc 患者）的血液。记录了血管并发症，如数字溃疡、肺动脉高压和硬皮病肾危象。通过体外和体内试验确定了循环NET与血管并发症之间的关系。研究还确定了合成前列环素类似物表前列醇对 NET 释放的影响。与无血管并发症的匹配患者相比，SSc相关血管并发症患者的中性粒细胞活化和NET释放均升高。中性粒细胞活化和NET与血管损伤的循环标志物可溶性E-选择素和VCAM-1呈正相关。用合成前列环素类似物治疗数字缺血患者可提高中性粒细胞环磷酸腺苷的活性，这与抑制NET释放和减少循环中的NET有关。我们的研究表明，NET 与 SSc 的血管并发症之间存在关联。我们还发现了合成前列环素类似物的另一种潜在治疗功效，即减少 SSc 患者中性粒细胞的过度活跃和 NET 的释放。
{"title":"Elevated neutrophil extracellular traps in systemic sclerosis-associated vasculopathy and suppression by a synthetic prostacyclin analog","authors":"Neda Kortam, Wenying Liang, Claire Shiple, Suiyuan Huang, Rosemary Gedert, James St. Clair, Cyrus Sarosh, Caroline Foster, Pei-Suen Tsou, John Varga, Jason S. Knight, Dinesh Khanna, Ramadan A. Ali","doi":"10.1186/s13075-024-03379-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03379-6","url":null,"abstract":"Neutrophils and neutrophil extracellular traps (NETs) contribute to the vascular complications of multiple diseases, but their role in systemic sclerosis (SSc) is understudied. We sought to test the hypothesis that NETs are implicated in SSc vasculopathy and that treatment with prostacyclin analogs may ameliorate SSc vasculopathy not only through vasodilation but also by inhibiting NET release. Blood from 125 patients with SSc (87 diffuse cutaneous SSc and 38 limited cutaneous SSc) was collected at a single academic medical center. Vascular complications such as digital ulcers, pulmonary artery hypertension, and scleroderma renal crisis were recorded. The association between circulating NETs and vascular complications was determined using in vitro and ex vivo assays. The impact of the synthetic prostacyclin analog epoprostenol on NET release was determined. Neutrophil activation and NET release were elevated in patients with SSc-associated vascular complications compared to matched patients without vascular complications. Neutrophil activation and NETs positively correlated with soluble E-selectin and VCAM-1, circulating markers of vascular injury. Treatment of patients with digital ischemia with a synthetic prostacyclin analog boosted neutrophil cyclic AMP, which was associated with the blunting of NET release and reduced NETs in circulation. Our study demonstrates an association between NETs and vascular complications in SSc. We also identified the potential for an additional therapeutic benefit of synthetic prostacyclin analogs, namely to reduce neutrophil hyperactivity and NET release in SSc patients. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"30 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.1186/s13075-024-03362-1
Yeo-Jin Song, Hyoungyoung Kim, Soo-Kyung Cho, Hye Won Kim, Chaewhi Lim, Eunwoo Nam, Chan-Bum Choi, Tae-Hwan Kim, Jae-Bum Jun, Sang-Cheol Bae, Dae Hyun Yoo, Su Jin Hong, Seung-Jin Yoo, Youkyung Lee, Yoon-Kyoung Sung
To determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD). Data were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth’s penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD. A total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16–3.10), baseline diffusing capacity for carbon monoxide (DLCO) < 60% (adjusted HR 4.88, 95% CI 1.11–45.94), and usual interstitial pneumonia (UIP) pattern (adjusted HR 5.13, 95% CI 1.00–57.36) were identified as risk factors for mortality in RA-ILD patients. Patients with RA-ILD have an elevated risk of mortality compared with those without ILD. Infection-related deaths are the main causes of mortality in this population. High RA activity, low DLCO, and the UIP pattern are significantly associated with the mortality in patients with RA-ILD.
目的：与患有类风湿性关节炎（RA）但无间质性肺病（RA-nonILD）的患者相比，确定韩国类风湿性关节炎（RA）相关间质性肺病（ILD）患者的死亡风险因素。数据摘自韩国一家学术转诊医院对接受过胸部计算机断层扫描的 RA 患者进行的单中心前瞻性队列研究。研究选取了2017年5月至2022年8月期间登记的RA-ILD患者，并选取了无ILD的患者作为比较对象。我们计算了死亡率，并调查了每例死亡的原因。我们使用Cox比例危险回归法和Firth惩罚似然法确定RA-ILD患者的死亡风险因素。共纳入了 615 名 RA 患者：其中200例患有ILD，415例未患有ILD。在RA-ILD组中，540.1人年中有15人死亡，死亡率为2.78/100人年。RA-非ILD组在1669.9人年中没有死亡报告。死亡的主要原因是感染（9 例）和肺癌（5 例），只有 1 例死亡归因于 ILD 恶化。高RA活性（调整后HR为1.87，CI为1.16-3.10）、基线一氧化碳弥散能力（DLCO）<60%（调整后HR为4.88，95% CI为1.11-45.94）和常见间质性肺炎（UIP）模式（调整后HR为5.13，95% CI为1.00-57.36）被认为是RA-ILD患者死亡的风险因素。与无 ILD 的患者相比，RA-ILD 患者的死亡风险较高。与感染相关的死亡是该人群死亡的主要原因。高RA活性、低DLCO和UIP模式与RA-ILD患者的死亡率显著相关。
{"title":"Risk factors of mortality in patients with rheumatoid arthritis-associated interstitial lung disease: a single-centre prospective cohort study","authors":"Yeo-Jin Song, Hyoungyoung Kim, Soo-Kyung Cho, Hye Won Kim, Chaewhi Lim, Eunwoo Nam, Chan-Bum Choi, Tae-Hwan Kim, Jae-Bum Jun, Sang-Cheol Bae, Dae Hyun Yoo, Su Jin Hong, Seung-Jin Yoo, Youkyung Lee, Yoon-Kyoung Sung","doi":"10.1186/s13075-024-03362-1","DOIUrl":"https://doi.org/10.1186/s13075-024-03362-1","url":null,"abstract":"To determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD). Data were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth’s penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD. A total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16–3.10), baseline diffusing capacity for carbon monoxide (DLCO) < 60% (adjusted HR 4.88, 95% CI 1.11–45.94), and usual interstitial pneumonia (UIP) pattern (adjusted HR 5.13, 95% CI 1.00–57.36) were identified as risk factors for mortality in RA-ILD patients. Patients with RA-ILD have an elevated risk of mortality compared with those without ILD. Infection-related deaths are the main causes of mortality in this population. High RA activity, low DLCO, and the UIP pattern are significantly associated with the mortality in patients with RA-ILD.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"35 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-18DOI: 10.1186/s13075-024-03378-7
George D Kalliolias, Athanasios G Papavassiliou
With great interest, we have read the recent article "Expression of HIF1α in intestinal epithelium restricts arthritis inflammation by inhibiting RIPK3-induced cell death machinery" published by Lyu et al. in Annals of the Rheumatic Diseases. The authors pose that the expression of hypoxia-inducible factor 1 alpha in intestinal epithelial cells represents a crucial check point for the development of arthritis by impeding necroptosis of intestinal epithelial cells and safeguarding the intestinal barrier integrity. Previous studies suggest a potential mechanistic link between faulty intestinal barrier function and potentiation of arthritogenic immune cells. From this perspective, bolstering the intestinal barrier integrity arose as an attractive therapeutic strategy for rheumatoid arthritis.
{"title":"Stabilizing the integrity of intestinal barrier to control arthritis.","authors":"George D Kalliolias, Athanasios G Papavassiliou","doi":"10.1186/s13075-024-03378-7","DOIUrl":"10.1186/s13075-024-03378-7","url":null,"abstract":"<p><p>With great interest, we have read the recent article \"Expression of HIF1α in intestinal epithelium restricts arthritis inflammation by inhibiting RIPK3-induced cell death machinery\" published by Lyu et al. in Annals of the Rheumatic Diseases. The authors pose that the expression of hypoxia-inducible factor 1 alpha in intestinal epithelial cells represents a crucial check point for the development of arthritis by impeding necroptosis of intestinal epithelial cells and safeguarding the intestinal barrier integrity. Previous studies suggest a potential mechanistic link between faulty intestinal barrier function and potentiation of arthritogenic immune cells. From this perspective, bolstering the intestinal barrier integrity arose as an attractive therapeutic strategy for rheumatoid arthritis.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"135"},"PeriodicalIF":4.9,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141722981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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