Rheumatology最新文献

{"title":"Fatigue levels and associated factors in systemic sclerosis: a cross-sectional study of 2,385 SPIN Cohort participants","authors":"Linda Kwakkenbos, Brooke Levis, Richard S Henry, Gabrielle Virgili-Gervais, Marie-Eve Carrier, Susan J Bartlett, Amy Gietzen, Karen Gottesman, Geneviève Guillot, Amanda Lawrie-Jones, Laura K Hummers, Vanessa L Malcarne, Maureen D Mayes, Michelle Richard, Robyn K Wojeck, Maureen Worron-Sauvé, Marie Hudson, Luc Mouthon, Andrea Benedetti, Brett D Thombs","doi":"10.1093/rheumatology/keae570","DOIUrl":"https://doi.org/10.1093/rheumatology/keae570","url":null,"abstract":"Objectives To compare fatigue in a large multinational systemic sclerosis (SSc) cohort to general population data and identify associated sociodemographic, lifestyle and SSc disease factors. Methods Scleroderma Patient-centered Intervention Network Cohort participants completed the Patient-Reported Outcomes Measurement Information System-29 v2.0 fatigue domain. T-scores were compared with the USA general population (mean = 50; SD = 10). Multivariable linear regression was used to assess associations with sociodemographic, lifestyle, and disease-related variables. Results Among 2,385 participants (mean age 54.9 (SD = 12.6) years, 87% female, 38% diffuse SSc), mean fatigue T-score was 54.6 (SD = 11.0); 438 (18%) reported mild fatigue, 641 (27%) moderate, and 180 (8%) severe fatigue. Fatigue was independently associated with sociodemographic factors age (-0.10 points per year, [95% CI -0.14;-0.07]), male sex (-1.67 points, [-2.96;-0.37]), non-married status (0.97 points [0.04; 1.89]), and country (reference USA; France -2.35 points [-3.48;-1.21] and UK 2.38 points [0.80; 3.97]), and lifestyle factors smoking (4.16 points [2.52; 5.80]), alcohol consumption (-0.18 points per drink per week [-0.28;-0.07]), and body-mass index (0.34 points per unit [0.27; 0.42]). Fatigue was associated with disease-related factors gastrointestinal involvement (4.21 points [2.99; 5.43]), digital ulcers (1.51 points, [0.25; 2.77]), moderate small joints contractures (1.41 points [0.13; 2.69]), rheumatoid arthritis (4.34 points [2.37–6.31]) and Sjögren’s syndrome (1.89 points [0.23; 3.55]). When pain was included in the model, its association was large (2.19 points [2.03; 2.34]) and interstitial lung disease was also associated (1.21 points [0.42; 2.00]). Conclusions In people with SSc, fatigue scores were substantially higher than the general population and associated with multiple disease factors including gastrointestinal involvement, several painful disease manifestations, and lung involvement.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"14 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489369","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}

{"title":"The place of JAK inhibitors in systemic juvenile idiopathic arthritis with lung disease (SJIA-LD): French experience","authors":"Gaëlle Côte, Pierre Quartier, Alexandre Belot, Isabelle Melki, Véronique Hentgen, Etienne Merlin","doi":"10.1093/rheumatology/keae589","DOIUrl":"https://doi.org/10.1093/rheumatology/keae589","url":null,"abstract":"Objectives A new form of systemic juvenile idiopathic arthritis (SJIA) with associated lung disease (SJIA-LD) has recently been described. Multiple lines of treatment have failed to yield satisfactory results for this disorder. JAK inhibitors (JAKis) have recently been approved for the treatment of JIA, but clinical evidence of their efficacy in SJIA-LD is still weak. Here we describe and assess real-life experience of SJIA-LD treatment with JAKis in France. Methods This is a retrospective study based on information gathered from patients’ medical records. Systemic and pulmonary symptoms, biological data including CRP, ferritin, IL18, chest CT scan, and functional respiratory tests were collected. Results Eight patients with SJIA-LD were identified in French pediatric rheumatology centers. All received at least one JAKi (baricitinib, ruxolitinib, and/or tofacitinib). Complete disease control was obtained in four patients. Steroids were tapered in four patients and stopped in two. Three patients presented an episode of MAS shortly after anti-IL1s were stopped when JAKis were introduced. Two patients had other serious side effects (viral reactivation—EBV, BK virus, cytopenia). At last follow-up, one patient had died from severe MAS, two patients had undergone hematopoietic stem cell transplantation, four were in complete response (two of them free of steroids), and one in partial response with JAKis. Lung response to JAKi was not clearly linked to disease duration. Conclusion JAKis offer another therapeutic option for patients with SJIA-LD. However, the risk of MAS argues for caution about stopping anti-IL1s when introducing JAKis. Tolerance needs careful monitoring in larger studies.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"97 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489371","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}

{"title":"Anti-peptide antibodies, anti-SNRK and anti-HUWE1 antibodies, as potential predictors of good response to tofacitinib therapy in rheumatoid arthritis patients","authors":"Po-Ku Chen, Yi-Ming Chen, Jeremy J W Chen, Der-Yuan Chen","doi":"10.1093/rheumatology/keae595","DOIUrl":"https://doi.org/10.1093/rheumatology/keae595","url":null,"abstract":"Objectives To maximize the cost-effectiveness of tofacitinib, one of Janus kinase inhibitors, there is an unmet need to identify predictors of therapeutic response. Utilizing phage immunoprecipitation sequencing (PhIP-Seq), we aim to identify peptide biomarkers for predicting good response to tofacitinib in rheumatoid arthritis (RA) patients. Methods We enrolled 106 patients who had received 24-week tofacitinib therapy, including twelve patients undergoing PhIP-Seq analysis in the discovery stage and ninety-four patients validated with enzyme-linked immunosorbent assay (ELISA) in the replication stage. Disease activity was assessed using the 28-joint disease activity score-erythrocyte sedimentation rate, and therapeutic response was evaluated using EULAR response criteria. Plasma levels of caspase-1 and IL-18 were determined using ELISA. Results PhIP-Seq analysis identified antibodies to sucrose non-fermenting-related kinase (SNRK) and HUWE1 (ubiquitin E3 ligase) as peptide biomarkers for discriminating good responders from the non-good responders. Using ELISA for validation on another cohort, an optimal cut-off value of anti-SNRK antibody for predicting good response was 0.381, with AUC 0.823, specificity 80.6%, and sensitivity 78.1% (p = 3.01E-07), and anti-HUWE1 antibody at 0.362, with AUC 0.740, specificity 74.2%, and sensitivity 62.5% (p < 0.001). Plasma levels of anti-SNRK and anti-HUWE1 antibodies were positively correlated with levels of caspase-1 and IL-18 (both p < 0.05). Multivariate logistic regression analysis revealed anti-SNRK antibody as a significant predictor of good therapeutic response. After tofacitinib therapy, anti-SNRK antibody levels significantly declined in good responders, but not in non-good responders. Conclusion We identify two peptide antibodies, anti-SNRK and anti-HUWE1 antibodies, as pretreatment predictors of good therapeutic response to tofacitinib in RA patients.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"1 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489576","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}

{"title":"Impact of baseline proteinuria level on long-term outcomes in lupus nephritis","authors":"Fadi Kharouf, Qixuan Li, Laura P Whittall Garcia, Dafna D Gladman, Zahi Touma","doi":"10.1093/rheumatology/keae579","DOIUrl":"https://doi.org/10.1093/rheumatology/keae579","url":null,"abstract":"Objectives Proteinuria is a marker of lupus nephritis (LN) activity and damage. We aimed to explore the impact of baseline proteinuria level on long-term outcomes. Methods We included 249 patients diagnosed with their first biopsy-proven LN. We divided patients based on baseline proteinuria into low-level (≤1 g/day, group 1; 62 patients), moderate-level (>1 and <3 g/day, group 2; 90 patients), and high-level proteinuria (≥3 g/day, group 3; 97 patients). Outcomes included complete proteinuria recovery (CPR) at 1 year, an adverse composite outcome (ESKD, a sustained ≥40% decline in eGFR, or death), and LN flares. Cox proportional hazard models were used to examine the association between baseline characteristics and long-term outcomes. Results At baseline, the median [IQR] age was 33.2 [26.4, 42.4] years; median proteinuria level was 2.2 [1.0, 3.8] g/day. 177 (71%) patients had proliferative lesions on biopsy; 59.7% in group 1, 78.9% in group 2, and 71.4% in group 3. The rate of achievement of CPR at 1 year was highest for group 1 and lowest for group 3. For long-term outcomes (median follow-up 8.4 years), the frequency of the adverse composite outcome was 27.4%, 26.7%, and 48.5% in groups 1, 2, and 3, respectively; p= 0.003. The corresponding frequency of flares was 27.4%, 38.2%, and 61.9%, respectively; p< 0.001. In the multivariable model for factors associated with long-term outcomes, there was no significant difference between groups 1 and 2; group 3 was associated with the worst prognosis. Conclusions Low-level proteinuria is commonly associated with proliferative LN and adverse long-term outcomes.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"5 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489577","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}

{"title":"Immunogenicity to Herpes Zoster recombinant subunit vaccine in immune-mediated rheumatic patients under treatment with JAK inhibitors","authors":"Cristiana Sieiro-Santos, Juan Garcia Herrero, Jose Ordas Martínez, Carolina Álvarez Castro, Alejandra López Robles, Ronald Colindres, Estefanía Robles Martín, Ana M Sahagun, Jose G Ruiz de Morales","doi":"10.1093/rheumatology/keae584","DOIUrl":"https://doi.org/10.1093/rheumatology/keae584","url":null,"abstract":"Objectives Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV), and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine, offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors. We aimed to characterize B cell and T cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK inhibitors, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection. Methods We investigated humoral, and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK inhibitors. The responses were compared with age, gender and disease-matched healthy controls. Results Patients with IMRDs treated with JAK inhibitors showed reduced seroconversion rate (63% vs 100% and lower VZV IgG titers (1222 ± 411 vs 3048 ± 556, p< 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (Granzyme A and/or Granzyme B secretion) immune responses were also significantly diminished in IMRDs patients. Negative correlation was found between VZV antibody titers and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative methotrexate and glucocorticoid doses, history of multiple DMARDs, and treatment duration with JAK inhibitors. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses. Conclusions Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK inhibitors. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against herpes zoster infection and VHZ reactivation.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"5 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489370","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}

{"title":"Prevalence and clinical value of autoantibodies directed against lysobisphosphatidic acid in antiphospholipid syndrome","authors":"Mathilde Lambert, Maxime Robin, Lucie Munier, Abdou Beziane, Jean-Louis Mège, Daniel Bertin, Nathalie Bardin","doi":"10.1093/rheumatology/keae588","DOIUrl":"https://doi.org/10.1093/rheumatology/keae588","url":null,"abstract":"Objectives To assess the prevalence and clinical significance of autoantibodies against lysobisphophatidic acid (aLBPA) in patients with antiphospholipid syndrome (APS). Methods We conducted a retrospective analysis involving 91 patients with persistent conventional antiphospholipid antibodies (aPL): 60 patients with at least one clinical event of APS (symptomatic group) and 31 without (asymptomatic group), as well as 33 aPL-negative controls. Detection of aLBPA in serum samples was performed using an enzyme-linked immunosorbent assay (ELISA) specifically designed for this study. Results The prevalence of aLBPA is significantly higher in patients with persistent aPL than that of the control group (p< 0.0001). Among patients with persistent aPL, our findings reveal a significantly higher prevalence of aLBPA in asymptomatic patients compared with their symptomatic counterparts (p= 0.027). Notably, patients positive for IgG aPL alone demonstrated a greater likelihood of presenting clinical events suggestive of APS. Conclusion The combined assay of aLBPA and conventional aPL could be used to stratify patients with persistent aPL. This combined approach could serve as a valuable tool in the management of this complex autoimmune disease, particularly in guiding decisions regarding the initiation of primary thromboprophylaxis in asymptomatic patients with persistent aPL.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"235 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488861","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}

{"title":"Multi-domain effectiveness of guselkumab evaluated via composite indices through 1 year in patients with PsA and inadequate response to TNFi: post hoc analysis of COSMOS","authors":"Laure Gossec, Xenofon Baraliakos, Daniel Aletaha, Mohamed Sharaf, Emmanouil Rampakakis, Frédéric Lavie, Clementina López-Medina, Carlo Selmi, Laura C Coates","doi":"10.1093/rheumatology/keae586","DOIUrl":"https://doi.org/10.1093/rheumatology/keae586","url":null,"abstract":"Objective Evaluate guselkumab efficacy, an anti-interleukin-23p19-subunit antibody, in patients with active psoriatic arthritis (PsA) and inadequate response to 1–2 tumour necrosis factor inhibitors (TNFi-IR), utilizing composite indices assessing disease activity across disease domains. Methods In the Phase IIIb COSMOS trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks through W44. Patients receiving placebo crossed over to guselkumab at W24. In this post-hoc analysis, composite indices evaluated included the Disease Activity Index for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Disease Activity Score (PASDAS), GRAPPA Composite score (GRACE), modified Composite Psoriatic Disease Activity Index (mCPDAI), minimal disease activity (MDA) and very low disease activity (VLDA). Through W24, treatment failure rules were applied. Through W48, non-responder imputation was used for missing data. Results Greater proportions of guselkumab- than placebo-randomized patients achieved composite index endpoints relating to low disease activity (LDA; 14.8–52.4% vs 3.1–28.1%) or remission (3.7–5.3% vs 0.0–2.1%) at W24. Among guselkumab-randomized patients, LDA rates increased to W48 (DAPSA, 44.4%; DAS28, 47.8%; PASDAS, 34.4%; GRACE, 33.3%; mCPDAI, 40.2%), and 27.0% and 64.0% achieved MDA and a PsARC response, respectively. In the placebo→guselkumab crossover group, W48 response rates were similar to the guselkumab-randomized group. Conclusion Guselkumab treatment provided substantial benefits across multiple disease domains, with increasing proportions of patients achieving LDA/remission over 1 year, highlighting the effectiveness of guselkumab despite previous inadequate response to TNFi.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"92 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487219","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}

{"title":"Arthroscopy has a higher discriminative capacity than MRI in detecting mild cartilage lesions","authors":"Irene Sánchez-Platero, Javier Fernández-Jara, Carmen Herencia, Javier Llorca, Aránzazu Mediero, Emilio Calvo, Raquel Largo, Gabriel Herrero-Beaumont","doi":"10.1093/rheumatology/keae591","DOIUrl":"https://doi.org/10.1093/rheumatology/keae591","url":null,"abstract":"Objectives To determine whether current magnetic resonance imaging (MRI) could detect superficial cartilage lesions that are observed during diagnostic arthroscopy in patients with knee pain who have not been diagnosed with joint disease. Methods Adult patients with knee pain of unclear origin lasting more than three months, scheduled for a therapeutic/diagnostic arthroscopy were recruited. Demographic and clinical data, pain assessment, MRI imaging, and observations of cartilage damage in the medial femoral condyle during arthroscopic procedure were documented. Patients were categorized based on the presence of cartilage damage assessed via MRI and/or direct visualization. Concordance between these assessments and its variation with age and patient-reported pain were examined. Results Out of the 95 patients recruited, 48 exhibited lesions in the medial femoral condyle (MFC) during arthroscopic examination, while only 24 of them showed lesions on the MRI scans. The thickness of the cartilage in the MFC was significantly lower in patients with cartilage damage detected by MRI compared with those without. Among patients with cartilage lesions identified during arthroscopy, those also showing lesions on the MRI had lower cartilage thickness and higher Outerbridge score than those without lesions on the MRI. Patients with detectable cartilage damage on the MRI were significantly older and reported higher levels of pain than those with damage detected only by arthroscopic examination. Conclusion Despite significant technological advancements in MRI, arthroscopy still proves superior in identifying mild structural cartilage lesions that are not identifiable by this technique.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"9 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487221","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}

{"title":"Severe cardiovascular manifestation of ASIA syndrome triggered by silicone breast implants.","authors":"Ágnes Szappanos, Ágota Hajas, Prof István Hartyánszky, Krisztina Kádár, Luca Kuthi, István Hartyánszky, Prof Béla Merkely, Anikó Ilona Nagy","doi":"10.1093/rheumatology/keae564","DOIUrl":"https://doi.org/10.1093/rheumatology/keae564","url":null,"abstract":"","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473621","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}

{"title":"RNA sequencing uncovers key players of cartilage calcification: potential implications for osteoarthritis pathogenesis.","authors":"Ilaria Bernabei, Elodie Faure, Julien Wegrzyn, Nicolas Bertheaume, Guillaume Falgayrac, Thomas Hugle, Sonia Nasi, Nathalie Busso","doi":"10.1093/rheumatology/keae587","DOIUrl":"https://doi.org/10.1093/rheumatology/keae587","url":null,"abstract":"<p><strong>Objective: </strong>Osteoarthritis (OA) is a joint disease linked with pathologic cartilage calcification, caused by the deposition of calcium-containing crystals by chondrocytes. Despite its clinical significance, the precise mechanisms driving calcification remain elusive. This study aimed to identify crucial players in cartilage calcification, offering insights for future targeted interventions against OA.</p><p><strong>Methods: </strong>Primary murine chondrocytes were stimulated with secondary calciprotein particles (CPP2) or left untreated (NT) for 6 h. Calcification was assessed by alizarin red staining. RNA was analyzed by Bulk RNA sequencing. Differentially expressed (DE) genes were identified (cutoff: abs(LogFC)>1 and adj.p-val < 0.05), and top 50 DE genes were cross-referenced with human OA datasets from previous studies (ie healthy vs OA cartilage, or undamaged vs damaged cartilage). RNA from NT and CPP2-stimulated primary human OA chondrocytes were used to validate genes by qPCR.</p><p><strong>Results: </strong>CPP2 induced crystal formation by chondrocytes and significantly modulated 1466 genes. Out of the top 50 DE genes in CPP2, 27 were confirmed in published OA cartilage datasets. Of those genes, some are described in calcification and/or OA (Errfi1, Ngf, Inhba, Col9a1). Two additional ones (Rcan1, Tnfrsf12a) appear novel and interesting in the context of calcification and OA. We validated modulation of these six genes in calcifying human chondrocytes from 5 patients. Ultimately, we unveiled two distinct gene families modulated by CPP2: the first comprised cytoskeletal genes (Actb, Tpm1, Cfl1, Tagln2, Lmna), while the second encompassed extracellular matrix genes (Fmod, Sparc, Col9a1, Cnmd).</p><p><strong>Conclusion: </strong>CPP2 modulates genes in chondrocytes that could represent new targets for therapeutic interventions in OA.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473620","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}