Rheumatology最新文献

{"title":"Magnetic resonance imaging patterns revealing muscle pathology and clinical features in idiopathic inflammatory myopathies.","authors":"Takashi Shimoyama, Ken Yoshida, Yoshinao Muro, Haruyasu Ito, Takayuki Matsushita, Yohsuke Oto, Taro Ukichi, Kentaro Noda, Daitaro Kurosaka","doi":"10.1093/rheumatology/keae125","DOIUrl":"10.1093/rheumatology/keae125","url":null,"abstract":"<p><strong>Objective: </strong>Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders significantly impacting skeletal muscles; however, the precise correlation between muscle magnetic resonance imaging (MRI) findings, muscle pathology, disease subtypes and clinical characteristics remains uncertain. Thus, we investigated the association of muscle MRI findings in IIMs with muscle pathology and clinical features.</p><p><strong>Methods: </strong>New-onset IIM patients underwent proximal upper and/or lower limb muscle MRI. Patterns of muscle oedema on MRI were categorised into fascial, honeycomb, peripheral, foggy, dense, or coarse dot patterns and compared with inflammatory cell infiltration sites in corresponding muscle biopsies. The incidence of MRI patterns was examined in patient subgroups using myositis-specific antibodies (MSAs) and 2017 EULAR/ACR classification criteria. Univariate and multivariate analyses were conducted to determine the odds ratios (ORs) of MRI findings for clinical characteristics.</p><p><strong>Results: </strong>Fifty-six of 85 patients underwent muscle biopsy. Foggy, honeycomb and fascial patterns at biopsy sites correlated with inflammatory cell infiltration in the endomysium (OR 11.9, P = 0.005), perimysium (OR 6.0, P = 0.014) and fascia (OR 16.9, P < 0.001), respectively. Honeycomb and foggy patterns were characteristic of patients with anti-TIF1γ or anti-Mi2 antibodies and MSA-negative dermatomyositis, and those with anti-SRP or anti-HMGCR antibodies and MSA-negative polymyositis (PM), respectively. The honeycomb pattern positively correlated with malignancy (OR 6.87, P < 0.001) and Gottron sign (OR 8.05, P = 0.002); the foggy pattern correlated with muscle weakness (OR 11.24, P = 0.005). The dense dot pattern was associated with dysphagia (OR 6.27, P = 0.006) and malignancy (OR 8.49, P = 0.002).</p><p><strong>Conclusion: </strong>Muscle MRI holds promise in predicting muscle pathology, disease subtypes and clinical manifestations of IIMs.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973273","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":"Ultrasound-based detection of inflammatory changes for early diagnosis and risk model construction of psoriatic arthritis.","authors":"Yiyi Wang, Nuozhou Liu, Lingyan Zhang, Min Yang, Yue Xiao, Furong Li, Hongxiang Hu, Li Qiu, Wei Li","doi":"10.1093/rheumatology/kead701","DOIUrl":"10.1093/rheumatology/kead701","url":null,"abstract":"<p><strong>Objectives: </strong>PsA is the most prevalent coexisting condition associated with psoriasis. Early-stage PsA patients always present unspecific and subtle clinical manifestations causing delayed diagnosis and leading to unfavourable health outcomes. The application of US enables precise identification of inflammatory changes in musculoskeletal structures. Hence, we constructed US models to aid early diagnosis of PsA.</p><p><strong>Methods: </strong>This was a cross-sectional study carried out in the Department of Dermatology at West China Hospital (October 2018-April 2021). All participants underwent thorough US examinations. Participants were classified into the under 45 group (18 ≤ age ≤ 45 years) and over 45 (age >45 years) group and then randomly grouped into derivation and test cohort (7:3). Univariable logistic regression, least absolute shrinkage and selection operator, and multivariable logistic regression visualized by nomogram were conducted in order. Receiver operating characteristic (ROC), calibration curve, decision curve analysis (DCA) and clinical impact curve analysis (CICA) were performed for model verification.</p><p><strong>Results: </strong>A total of 1256 participants were included, with 767 participants in the under 45 group and 489 in the over 45 group. Eleven and 16 independent ultrasonic variables were finally selected to construct the under 45 and over 45 model with the area under the ROC of 0.83 (95% CI 0.78-0.87) and 0.83 (95% CI 0.78-0.88) in derivation cohort, respectively. The DCA and CICA analyses showed good clinical utility of the two models.</p><p><strong>Conclusion: </strong>The implementation of the US models could streamline the diagnostic process for PsA in psoriasis patients, leading to expedited evaluations while maintaining diagnostic accuracy.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037970","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":"Systemic lupus erythematosus patients have unique changes in serum metabolic profiles across age associated with cardiometabolic risk.","authors":"Elizabeth C Jury, Junjie Peng, Alexandra Van Vijfeijken, Lucia Martin Gutierrez, Laurel Woodridge, Chris Wincup, Ines Pineda-Torra, Coziana Ciurtin, George A Robinson","doi":"10.1093/rheumatology/kead646","DOIUrl":"10.1093/rheumatology/kead646","url":null,"abstract":"<p><strong>Objectives: </strong>Cardiovascular disease through accelerated atherosclerosis is a leading cause of mortality for patients with systemic lupus erythematosus (SLE), likely due to increased chronic inflammation and cardiometabolic defects over age. We investigated age-associated changes in metabolomic profiles of SLE patients and healthy controls (HCs).</p><p><strong>Methods: </strong>Serum NMR metabolomic profiles from female SLE patients (n = 164, age = 14-76) and HCs (n = 123, age = 13-72) were assessed across age by linear regression and by age group between patients/HCs (Group 1, age ≤ 25, n = 62/46; Group 2, age = 26-49, n = 50/46; Group 3, age ≥ 50, n = 52/31) using multiple t tests. The impact of inflammation, disease activity and treatments were assessed, and UK Biobank disease-wide association analysis of metabolites was performed.</p><p><strong>Results: </strong>Age-specific metabolomic profiles were identified in SLE patients vs HCs, including reduced amino acids (Group 1), increased very-low-density lipoproteins (Group 2), and increased low-density lipoproteins (Group 3). Twenty-five metabolites were significantly altered in all SLE age groups, dominated by decreased atheroprotective high-density lipoprotein (HDL) subsets, HDL-bound apolipoprotein (Apo)A1 and increased glycoprotein acetyls (GlycA). Furthermore, ApoA1 and GlycA were differentially associated with disease activity and serological measures, as well as atherosclerosis incidence and myocardial infarction mortality risk through disease-wide association. Separately, glycolysis pathway metabolites (acetone/citrate/creatinine/glycerol/lactate/pyruvate) uniquely increased with age in SLE, significantly influenced by prednisolone (increased pyruvate/lactate) and hydroxychloroquine (decreased citrate/creatinine) treatment and associated with type 1 and type 2 diabetes by disease-wide association.</p><p><strong>Conclusions: </strong>Increasing HDL (ApoA1) levels through therapeutic/nutritional intervention, whilst maintaining low disease activity, in SLE patients from a young age could improve cardiometabolic disease outcomes. Biomarkers from the glycolytic pathway could indicate adverse metabolic effects of current therapies.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482947","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":"Vasculitic neuropathy-related disability, pain, quality of life, and autonomic symptoms: a survey of 312 patients.","authors":"Michael P Collins, Robert D M Hadden, Raashid A Luqmani","doi":"10.1093/rheumatology/keae038","DOIUrl":"10.1093/rheumatology/keae038","url":null,"abstract":"<p><strong>Objectives: </strong>To assess self-reported symptoms of neuropathy, disability, pain, health-related quality of life (HR-QOL) and autonomic dysfunction in patients with vasculitis.</p><p><strong>Methods: </strong>Patients with vasculitis (with or without neuropathy) were invited by Vasculitis UK to complete an anonymous online survey.</p><p><strong>Results: </strong>Three hundred and twelve patients (71% female) responded. Median age was 61-70 years. Median duration of vasculitis was 4 years (<2 months to >15 years). Vasculitic types included granulomatosis with polyangiitis (34%), unspecified ANCA-associated vasculitis (13%), microscopic polyangiitis (11%), eosinophilic granulomatosis with polyangiitis (11%), giant cell arteritis (10%), non-systemic vasculitic neuropathy (2%) and other (19%). Many patients reported foot/hand symptoms suggestive of neuropathy, including numbness (64%), pain (54%) or weakness (40%). Two hundred and forty-two patients (78%) met our definition of probable vasculitic neuropathy: diagnosis of neuropathy by vasculitis team OR numbness OR weakness in feet/hands. Only 52% had been formally diagnosed with neuropathy. Compared with 70 patients without neuropathy, neuropathy patients had greater disability measured by the inflammatory Rasch-built Overall Disability Scale (centile mean 63.1 [s.d. 17.3] vs 75.2 [16.7]; P < 0.0001), Inflammatory Neuropathy Cause and Treatment scale (median 2 [interquartile range 1-4] vs 0.5 [0-2]; P < 0.0001) and modified Rankin scale (median 2 [interquartile range 1-3] vs 2 [1-2)]; P = 0.0002); greater pain on an 11-point rating scale (mean 4.6 [s.d. 2.6] vs 3.5 [2.8]; P = 0.0009); and poorer HR-QOL on the EQ5D-3L (summary index mean 0.58 [s.d. 0.29] vs 0.69 [0.28]; P < 0.0001). Two-thirds reported autonomic symptoms (not associated with neuropathy).</p><p><strong>Conclusion: </strong>Neuropathy is common and associated with significant disability, pain and impaired HR-QOL in patients with systemic vasculitis.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642867","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":"Risk of cardiovascular disease decreases over time in psoriatic arthritis but not in spondylarthritis: meta-analysis of longitudinal studies.","authors":"Hélène Gouze, Philippe Aegerter, Yasmine Gouyette, Maxime Breban, Maria Antonietta D'Agostino","doi":"10.1093/rheumatology/keae080","DOIUrl":"10.1093/rheumatology/keae080","url":null,"abstract":"<p><strong>Objective: </strong>SpA and PsA represent two frequent inflammatory rheumatic disorders characterized by an increased burden on quality of life due to the association of several comorbidities, especially cardiovascular disease (CVD). The estimated prevalence of CVD ranges from 12 to 19% and differs between the two diseases, however, the incidence of CVD is not completely known. We aimed to systematically review the literature and perform a meta-analysis of controlled observational studies to assess the incidence rate of CVD over time in SpA and PsA.</p><p><strong>Methods: </strong>We performed a systematic literature review (SLR) of longitudinal studies with a study period of at least 5 years, including SpA/PsA patients and general population. The main outcome was the occurrence of CVD, including ischaemic heart disease, stroke and death from CV causes. We then performed a random-effects model for meta-analysis.</p><p><strong>Results: </strong>The SLR included 34 articles, mainly focused on the association between SpA/PsA and CVD. Twenty-four articles were then selected for the meta-analysis. The overall incidence of CVD was increased in PsA [hazard ratio (HR) 1.28 (95% CI 1.15, 1.43)] and in SpA [HR 1.45 (95% CI 1.22, 1.72)] compared with the general population, with consistency across the different types of CVDs. Interestingly the incidence tended to decrease over time in PsA but not in SpA.</p><p><strong>Conclusion: </strong>The SLR and meta-analysis confirmed the increased incidence of CVD in both SpA and PsA patients compared with the general population, although the increase seems to be less prominent in PsA than in SpA. Future studies are needed to confirm our findings.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898195","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":"Therapeutic strategies and outcomes in neuropsychiatric systemic lupus erythematosus: an international multicentre retrospective study.","authors":"Alessandra Bortoluzzi, Antonis Fanouriakis, Ettore Silvagni, Simone Appenzeller, Linda Carli, Greta Carrara, Alberto Cauli, Fabrizio Conti, Lilian Teresa Lavras Costallat, Ginevra De Marchi, Andrea Doria, Micaela Fredi, Franco Franceschini, Carlo Garaffoni, John G Hanly, Marta Mosca, Elana Murphy, Matteo Piga, Luca Quartuccio, Carlo Alberto Scirè, Paola Tomietto, Simona Truglia, Anna Zanetti, Margherita Zen, George Bertsias, Marcello Govoni","doi":"10.1093/rheumatology/keae119","DOIUrl":"10.1093/rheumatology/keae119","url":null,"abstract":"<p><strong>Objectives: </strong>The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptoms severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation.</p><p><strong>Methods: </strong>This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis.</p><p><strong>Results: </strong>The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, P = 0.04). Age at diagnosis and focal central events emerged as additional response predictors.</p><p><strong>Conclusion: </strong>NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944387","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":"Histopathological comparison of Sjögren-related features between paired labial and parotid salivary gland biopsies of sicca patients.","authors":"Uzma Nakshbandi, Martha S van Ginkel, Gwenny M P J Verstappen, Fred K L Spijkervet, Suzanne Arends, Erlin A Haacke, Silvia C Liefers, Arjan Vissink, Hendrika Bootsma, Frans G M Kroese, Bert van der Vegt","doi":"10.1093/rheumatology/keae154","DOIUrl":"10.1093/rheumatology/keae154","url":null,"abstract":"<p><strong>Objectives: </strong>To compare focus score and other histopathological features between paired labial and parotid salivary gland biopsies in a diagnostic cohort of suspected Sjögren's disease (SjD) patients.</p><p><strong>Methods: </strong>Labial and parotid salivary gland biopsies were simultaneously obtained from patients with sicca complaints, suspected of having SjD. Biopsies were formalin fixed and paraffin embedded. Sections were stained with haematoxylin & eosin, and for CD3, CD20, CD45, cytokeratin, CD21, Bcl6, activation-induced deaminase (AID) and IgA/IgG. Focus score and other histopathological features characteristic for SjD were analysed.</p><p><strong>Results: </strong>Based on the expert opinion of three experienced rheumatologists, 36 patients were diagnosed as SjD and 63 as non-SjD sicca patients. When taking all patients together, absolute agreement of various histopathological features between labial and parotid biopsies was high and varied between 80% (focus score) and 93% [(pre-)lymphoepithelial lesions (LELs)]. More labial gland biopsies had a focus score ≥1 compared with their parotid counterpart. Accordingly, the area of infiltrate was larger in labial gland biopsies. When considering only SjD patients, labial glands contained significantly fewer B-lymphocytes and germinal centres/mm2, and less severe LELs compared with parotid glands.</p><p><strong>Conclusion: </strong>Labial and parotid glands from SjD patients contain similar histopathological key features, and thus both glands can be used for diagnosis and classification of SjD. However, parotid salivary glands reveal more evident B-lymphocyte-related features, while labial glands exhibit more inflammation, which may be partially unrelated to SjD.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306746","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":"Shelterin dysfunction promotes CD4+ T cell senescence in Behçet's disease.","authors":"Jing Shi, Menghao Zhang, Lili Zhang, Xin Yu, Luxi Sun, Jinjing Liu, Yan Zhao, Wenjie Zheng","doi":"10.1093/rheumatology/kead703","DOIUrl":"10.1093/rheumatology/kead703","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the potential role of shelterin dysfunction in naïve CD4+ T cells in the pathogenesis of Behçet's disease (BD).</p><p><strong>Methods: </strong>Naïve CD4+ T cells were isolated from 40 BD patients and 40 sex- and age-matched healthy controls (HC). Senescent profiles, shelterin subunits expression, telomere length, telomerase activity and critical DNA damage response (DDR) were evaluated. Telomere repeat factor-2 (TRF2) silencing was conducted for further validation.</p><p><strong>Results: </strong>Compared with HC, BD patients had significantly decreased naïve CD4+ T cells, increased cell apoptosis, senescence, and productions of TNF-α and IFN-γ upon activation. Notably, BD naïve CD4+ T cells had shortened telomere, impaired telomerase activity, and expressed lower levels of shelterin subunits TRF2, TRF1- and TRF2-Interacting Nuclear Protein 2 (TIN2) and Repressor/Activator Protein 1 (RAP1). Furthermore, BD naïve CD4+ T cells exhibited significantly increased DDR, evidenced by elevated phosphorylated ataxia telangiectasia (AT) mutated (pATM), phosphorylated p53 (pp53) and p21. Finally, TRF2 silencing markedly upregulated DDR, apoptosis and proinflammatory cytokines production in HC naïve CD4+ T cells.</p><p><strong>Conclusion: </strong>Our study demonstrated that TRF2 deficiency in BD naïve CD4+ T cells promoted cell apoptosis and senescence, leading to proinflammatory cytokines overproduction. Therefore, restoring TRF2 might be a promising therapeutic strategy for BD.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037957","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 information required by people with inflammatory arthritis when taking Methotrexate: a mixed-methods systematic review.","authors":"Sarah J Logan, Samantha Hider, Julie Green, Sarah J Ryan","doi":"10.1093/rheumatology/keae055","DOIUrl":"10.1093/rheumatology/keae055","url":null,"abstract":"<p><strong>Objectives: </strong>This mixed-methods systematic review aimed to identify and synthesize knowledge of the characteristics, content, and preferred format of information to support people with inflammatory arthritis (IA) to take MTX.</p><p><strong>Methods: </strong>A literature search using MEDLINE, The Cochrane Library, EMBASE, CINAHL, PsychInfo, GreyEU, Web of Science and Open Dissertation was conducted to identify all studies published from 2000 to December 2022. Included studies detailed factors related to MTX information needs of people aged ≥18 years with IA published in English. The Joanna Briggs Institute Guidelines (JBI) for convergent integrated mixed-methods systematic reviews were followed using validated tools for data extraction and quality. The data was analysed using reflexive thematic analysis.</p><p><strong>Results: </strong>Thirteen studies (seven quantitative, two mixed-methods and four qualitative) were included, involving 3425 adults, mainly female n = 2434 (71%), age 20-84 years. An overarching theme of a requirement for person-centred care was developed, with three interlinking themes: (1) accepting the need for treatment with MTX, (2) concerns about taking MTX, and (3) a need for tailored information and support. Limitations of the evidence included the use of heterogeneous outcome measures and instruments for measuring information needs.</p><p><strong>Conclusion: </strong>People with IA have individual, multifaceted information and support needs about MTX that are often unresolved when a one-size-fits-all approach is used. The findings of this review can inform rheumatology training to support a person-centred approach to identifying and addressing the specific needs and concerns and development of consistent easy-to-understand accessible MTX information.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698192","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-carbamylated protein antibodies drive AEC II toward a profibrotic phenotype by interacting with carbamylated TLR5.","authors":"Wei Xu, Minghua Huang, Rongrong Dong, Suyan Yan, Yan An, Baocheng Liu, Zhenzhen Ma, Kun Mu, Qingrui Yang","doi":"10.1093/rheumatology/keae111","DOIUrl":"10.1093/rheumatology/keae111","url":null,"abstract":"<p><strong>Objectives: </strong>This study looked at the role of anti-carbamylated protein (anti-CarP) antibodies in contributing to lung fibrosis in CTD-associated interstitial lung disease (ILD) in an autoantigen-dependent manner.</p><p><strong>Methods: </strong>ELISA was used to test serum samples, including 89 from the CTD-ILD group and 170 from the non-CTD-ILD group, for anti-CarP levels. Male C57BL/6 mice were used for the pulmonary fibrosis model and anti-CarP treatment in vivo (n = 5) and patient serum-derived or commercialized anti-CarP was used for cell treatment. We identified the carbamylated membrane protein via immunofluorescence (IF) and co-immunoprecipitation followed by mass spectrometry (MS) analysis. Quantitative RT-PCR, IF and western blot were performed to explore the antigen-dependent role of anti-CarP. A native electrophoretic mobility shift assay and MS analysis were used to verify direct interaction and carbamylation sites.</p><p><strong>Results: </strong>A significantly higher serum anti-CarP level was observed in CTD with ILD than without ILD. In vivo, intrapulmonary delivery of anti-CarP induces epithelial-mesenchymal transition (EMT) and microfibrotic foci. Carbamylation was enriched in type II alveolar epithelial cells (AEC II). A novel carbamylated membrane receptor, specifically recognized by anti-CarP, was identified as toll-like receptor 5 (TLR5). We found anti-CarP induces the nuclear translocation of NF-κB and downstream events, including EMT and expression of inflammatory cytokines in AEC II, which were reversed by TLR5 blocking or TLR5 knockdown. Moreover, up to 12 lysine carbamylation sites were found in TLR5 ectodomain, allowing the interaction of anti-CarP with carbamylated TLR5.</p><p><strong>Conclusions: </strong>Overall, we found anti-CarP drives aberrant AEC II activation by interacting with carbamylated TLR5 to promote ILD progression.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898194","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}