medRxiv - Rheumatology最新文献

{"title":"Reduced response to SARS-CoV-2 vaccination is associated with impaired immunoglobulin class switch recombination in SLE patients","authors":"Guillem Montamat, Claire E. Meehan, Hannah F. Bradford, Resit Yildirim, Francisca Guimaraes, Marina Johnson, David Goldblatt, David A. Isenberg, Claudia Mauri","doi":"10.1101/2024.08.14.24310924","DOIUrl":"https://doi.org/10.1101/2024.08.14.24310924","url":null,"abstract":"Background: Systemic Lupus Erythematosus (SLE) patients exhibit B-cell abnormalities. Although there are concerns about reduced antibody responses to SARS-CoV-2 vaccines, detailed data on B-cell-specific responses in SLE remain scarce. Understanding the responsiveness to novel vaccine-antigens, and boosters number, is important to avoid unnecessary prolonged isolation of immunocompromised individuals.\u0000Objectives: To assess humoral and antigen-specific B-cell subset responses, including changes in isotype switching, prior to and after several doses of SARS-CoV-2 vaccines.\u0000Methods: Blood samples were obtained prior to and after SARS-CoV-2 vaccination from cross-sectional and longitudinal cohorts of previously uninfected patients with SLE. Healthy participants receiving SARS-CoV-2 vaccines were recruited as controls. We measured serum antibody titres, their neutralizing capacity, and vaccine-specific memory B cells subsets.\u0000Results: Impaired IgG, IgA, and neutralizing responses against the original and various SARS-CoV-2 variants were observed following two doses of vaccine in SLE patients. Follow-up booster doses increased humoral responses compared to baseline, but they remained lower, with poorer neutralisation capacity against most strains, compared to healthy individuals after three or more doses. Analysis of memory B-cells subsets in SLE patients revealed an increase of SARS-CoV-2-specific isotype unswitched IgM+ over SARS-CoV-2-specific isotype switched IgG+/IgA+memory B-cells compared to healthy individuals. Culturing healthy naive B-cells with high levels of IFNα, a hallmark of SLE pathogenesis, prevented B-cells from switching to IgG under IgG-polarizing conditions.\u0000Conclusions: SLE patients' protection against SARS-CoV-2 is overall impaired compared to healthy individuals and is associated with a class switch defect possibly due to chronic exposure of B-cells to IFNα.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between sleep-disordered breathing and moderate to severe depression in systemic lupus erythematosus: the TRUMP2-SLE study","authors":"Yuichi Ishikawa, Nao Oguro, Takanori Ichikawa, Dai Kishida, Natsuki Sakurai, Chiharu Hidekawa, Kenta Shidahara, Keigo Hayashi, Yoshia Miyawaki, Yasuhiro Shimojima, Ryusuke Yoshimi, Ken-ei Sada, Nobuyuki Yajima, Noriaki Kurita","doi":"10.1101/2024.08.20.24312299","DOIUrl":"https://doi.org/10.1101/2024.08.20.24312299","url":null,"abstract":"Objective: Depression is the most frequent mood disorder that impairs quality of life and medication adherence in patients with systemic lupus erythematosus (SLE). Although sleep-disordered breathing (SDB) is a contributor to depression in the general population, its prevalence in SLE patients and its impact on depression are not clear. We employed a clinical epidemiologic approach to examine them in a multicenter cohort of SLE patients.\u0000Methods: This was a cross-sectional study of 414 Japanese adults with SLE at five university hospitals. The main exposure was high-risk SDB, assessed with the Berlin Questionnaire. The main outcome was moderate to severe depression assessed using the Patient Health Questionnaire-9. Poisson regression models were fitted with a robust error variance to estimate adjusted prevalence ratios (aPRs).\u0000Results: The mean age was 47.5 years and the mean body mass index (BMI) was 22.1 kg/m2. The prevalence of high-risk SDB was 15.2% (95% confidence interval [95% CI] 11.9%-19.0%). The prevalence of moderate or severe depression was 19.1% (95% CI 15.4%-23.2%). High-risk SDB was associated with a greater likelihood of moderate to severe depression (aPR 2.62, 95% CI 1.62-4.24). All the 1-, 2-, and 3-positive risk categories for SDB were associated with moderate to severe depression, in a dose-dependent manner. Conclusion: Among patients with SLE, SDB is common, and high-risk SDB is strongly associated with moderate to severe depression. The signs and symptoms of SDB should prompt a simultaneous evaluation for concomitant depression.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trust in Health Information Sources Among Patients with Systemic Lupus Erythematosus in the Social Networking Era: The TRUMP2-SLE Multicentre Study","authors":"Takanori Ichikawa, Dai Kishida, Yasuhiro Shimojima, Nobuyuki Yajima, Nao Oguro, Ryusuke Yoshimi, Natsuki Sakurai, Chiharu Hidekawa, Ken-ei Sada, Yoshia Miyawaki, Keigo Hayashi, Kenta Shidahara, Yuichi Ishikawa, Yoshiki Sekijima, Noriaki Kurita","doi":"10.1101/2024.08.17.24312148","DOIUrl":"https://doi.org/10.1101/2024.08.17.24312148","url":null,"abstract":"Objectives\u0000The rise of social networking services (SNS) has significantly impacted how patients with systemic lupus erythematosus (SLE) acquire health information, potentially influencing their discussions with healthcare providers. This study aimed to identify the preferences, actual access, and trust levels in various health information sources among SLE patients, along with associated factors. Methods\u0000A cross-sectional study was conducted from June 2020 to August 2021 across five university medical centres in Japan, involving 510 SLE patients aged 20 years and older. The study measured access to and preferences for health information sources, including SNS, and assessed trust in these sources. Factors influencing, such as internet usage and health literacy (HL) (functional, communicative, and critical), were analyzed using Poisson regression with robust error variance. Results\u0000Among the respondents, 98.2% expressed trust in doctors, whereas lower trust was observed in websites/blogs (52.0%) and SNS (26.9%). Despite this, the internet was the most frequent initial source of health information (45.3%), encompassing medical institutions' homepages, patient blogs, Twitter, and Instagram. Longer internet use was linked to increased trust in homepages/blogs and SNS. Higher functional HL correlated with greater trust in doctors and lower trust in websites/blogs and SNS, while higher communicative HL was associated with increased trust in doctors, homepages, and blogs. Conclusion\u0000Many SLE patients seek online health information, including SNS, before consulting rheumatologists. Internet usage duration and multidimensional HL influence trust in online health information sources. Rheumatologists and healthcare providers should account for these factors when disseminating health information and engaging with patients.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"177 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies towards HFE and SYT5 in anti-neutrophil cytoplasm antibody-associated vasculitis relapse","authors":"Shaghayegh Bayati, Jamsheela Nazer, James Ng, Michael Hayes, Mark A Little, Peter Nilsson, Elisa Pin","doi":"10.1101/2024.07.25.24310702","DOIUrl":"https://doi.org/10.1101/2024.07.25.24310702","url":null,"abstract":"Objective: Identification of those at high and low risk of disease relapse is a major unmet need in the management of patients with ANCA-associated vasculitis (AAV). Precise stratification would allow tailoring of immunosuppressive medication. We profiled the autoantibody repertoire of AAV patients in remission to identify novel autoantibodies associated with relapse risk. Methods: Plasma samples collected from AAV patients in remission were screened for novel autoantibodies using in-house generated protein arrays including 42,000 protein fragments representing 18,000 unique human proteins. Patients were categorized based on the occurrence and frequency of relapses. We modelled the association between these antibodies and relapse occurrence using descriptive and high dimensional regression approaches. Results: We observed nine autoantibodies at higher frequency in samples from AAV patients experiencing multiple relapses compared to patients in long-term remission off therapy (LTROT). LASSO analysis identified six autoantibodies that exhibited an association with relapse occurrence after sample collection. Antibodies targeting HFE and SYT5 were identified as associated with relapse in both analyses. Conclusion: Through a broad protein array-based autoantibody screening, we identified two novel autoantibodies as candidate biomarkers of relapse in AAV.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141785445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Registration of Trials: Where we are, why, and how we could get better","authors":"Denis Mongin, Diana Buitrago-Garcia, Sami Capderou, Thomas Agoritsas, Delphine Shophie Courvoisier, Michele Iudici","doi":"10.1101/2024.07.24.24310935","DOIUrl":"https://doi.org/10.1101/2024.07.24.24310935","url":null,"abstract":"Objectives: Transparent trial conduct requires prospective registration of a randomized controlled trial before the enrolment of the first participant. Registration aims to minimize potential biases through unjustified or hidden modification of trial design. We aimed to (1) estimate the proportion of randomized controlled trials that are prospectively registered and determine the time trends and the factors associated with prospective registration; (2) evaluate the reasons for non-adherence with prospective registration and explore potential mechanisms to enhance adherence with prospective registration. We studied trials published in rheumatology as a case study.\u0000Design and setting: We searched for reports of trials in rheumatology published between January 2009 and December 2022 using MEDLINE-PubMed. We retrieved trial registration numbers using metadata and reviewed full texts. We conducted a multivariable logistic regression to identify factors associated with prospective trial registration. We sent an online survey to authors of trials that were not prospectively registered. We inquired about possible reasons for non-adherence with prospective registration and asked about potential solutions. Results: We identified 1093 primary reports of randomized controlled trials; 453 (41.4%) were not prospectively registered. Of these, 130 (11.9%) were not registered, and 323 (29.5%) were retrospectively registered. Prospective registration increased over time at a rate of 3% per year (p<0.001), with only 13.3% (2/15) trials prospectively registered in 2009 to 73.2% (112/153) trials in 2022. Even among journals publicly supporting ICMJE recommendation, 16% of the trials published in 2022 were not prospectively registered. In the multivariable model, prospective registration was associated with a larger sample size, recruitment conducted across countries, and publication in a journal with a higher impact factor. Trial evaluating non pharmaceutical intervention, especially education, delivery of health care or wellness, had a lower rate of prospective registration. Investigators reported lack of knowledge, or organizational problems as the main reasons for retrospective registration. Authors also suggested linking ethical approval to trial registration as the best option to ensure prospective registration. Conclusions: Despite significant improvement, adherence to prospective registration remains unsatisfactory in rheumatology. Different strategies targeting journal editors, healthcare professionals, and researchers may improve trial registration.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141776059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Phenotype GWAS Supports Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis","authors":"Yiming Luo, Atlas Khan, Lili Liu, Cue Hyunkyu Lee, Gabriel J. Perreault, Sydney F. Pomenti, Pravitt Gourh, Krzysztof Kiryluk, Elana J. Bernstein","doi":"10.1101/2024.07.01.24309721","DOIUrl":"https://doi.org/10.1101/2024.07.01.24309721","url":null,"abstract":"Objective\u0000An increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross-phenotype GWAS meta-analysis. Methods\u0000We performed cross-phenotype GWAS meta-analysis and colocalization analysis for SSc and PBC. We performed both genome-wide and locus-based analysis, including tissue and pathway enrichment analyses, fine-mapping, colocalization analyses with expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets, and phenome-wide association studies (PheWAS). Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci. Results\u0000We detected a strong genetic correlation between SSc and PBC (rg = 0.84, p = 1.7 x 10-6). In the cross-phenotype GWAS meta-analysis, we identified 44 non-HLA loci that reached genome-wide significance (p < 5 x 10-8). Evidence of shared causal variants between SSc and PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40, ERAP1, PLD4, SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans-pQTLs of multiple plasma proteins involved in B cell function. Conclusion\u0000Our study supports a strong shared genetic susceptibility between SSc and PBC. Through cross-phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The BRoccoli In Osteoarthritis (BRIO study) - A randomised controlled feasibility trial to examine the potential protective effect of broccoli bioactives, (specifically sulforaphane), on osteoarthritis.","authors":"Rose K Davidson, Laura Watts, Gemma Beasy, shikha Saha, Paul Kroon, Aedin Cassidy, Allan Clark, William Fraser, Iain Mcnamara, Sarah R Kingsbury, Philip G Conaghan, Ian M Clark, Alex J MacGregor","doi":"10.1101/2024.06.20.24309233","DOIUrl":"https://doi.org/10.1101/2024.06.20.24309233","url":null,"abstract":"Objective\u0000The Broccoli in Osteoarthritis (BRIO Study) was conducted to determine whether dietary sulforaphane (SFN), consumed as broccoli, improves pain and/or physical function in participants with knee osteoarthritis (OA). This was a proof of principle study to test the feasibility of the trial to optimise the design of an appropriately powered study.\u0000Design\u0000Two-centre, double-blind, two-arm parallel, randomised placebo-controlled, dietary intervention feasibility trial. Patients with radiographic knee osteoarthritis (Kellgren-Lawrence score 2-3), with pain of at least 4 on a scale of 0-10 were recruited. The intervention was a high glucoraphanin broccoli, (source of SFN), or a matched placebo (no SFN) soup. Pain and measures of physical function were measured at baseline, 6 and 12 weeks. Results\u0000The mean WOMAC pain score (scale 0 - 20) was decreased by 4.2 (95% CI: 1.03,7.38) following intervention, Similar patterns of improvement were observed for other pain and function outcome measures. Study data, sample collections and intervention adherence were 100% compliant except where COVID restrictions applied. Acceptability for randomisation was 100% and acceptability for the intervention was 92%. There were three related adverse events, two of which were expected. Conclusions\u0000High glucosinolate broccoli soup is a novel approach to managing OA that is widely accessible and can be used on a large scale. This study shows that it is an acceptable way of delivering dietary bioactives and has potential for therapeutic benefit. The primary outcome of pain improved in the intervention group compared to the placebo and the confidence interval encompassed the minimal clinically important difference. The data provide justification for proceeding to a large scale, appropriately powered intervention trial.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141510818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weight Gain Following a Diagnosis of Anti-neutrophil Cytoplasm Antibody-Associated Vasculitis","authors":"Tania Salehi, Thomas French, Tariq E Farrah, Neeraj Dhaun, Robert W Hunter","doi":"10.1101/2024.05.29.24308107","DOIUrl":"https://doi.org/10.1101/2024.05.29.24308107","url":null,"abstract":"<strong>Objectives</strong> Patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) are at increased long-term risk of cardiometabolic diseases. The prevalence of obesity in AAV has not been well documented. We aimed to characterise change in body weight following a diagnosis of active AAV and to determine the risk factors for this.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occupation Recognition and Exploitation in Rheumatology Clinical Notes: Employing Deep Learning Models for Named Entity Recognition and Knowledge Discovery in Electronic Health Records","authors":"Alfredo Madrid-García, Inés Pérez-Sancristóbal, Leticia-Leon, Lydia-Abásolo, Benjamín Fernández-Gutiérrez, Luis Rodríguez-Rodríguez","doi":"10.1101/2024.05.08.24306389","DOIUrl":"https://doi.org/10.1101/2024.05.08.24306389","url":null,"abstract":"Occupation is considered a Social Determinant of Health (SDOH) and its effects have been studied at multiple levels. Although the inclusion of such data in the Electronic Health Record (EHR) is vital for the provision of clinical care, specially in rheumatology where work disability prevention is essential, occupation information is often either not routinely documented or captured in an unstructured manner within conventional EHR systems. Encouraged by recent advances in natural language processing and deep learning models, we propose the use of novel architectures (i.e., transformers) to detect occupation mentions in rheumatology clinical notes of a tertiary hospital, and to whom those occupations belongs. We also aimed to evaluate the clinical and demographic characteristics that influence the collection of this SDOH; and the association between occupation and patients’ diagnosis. Bivariate and multivariate logistic regression analysis were conducted for this purpose.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"129 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140930626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Pharmacokinetics, Biomarker Response, and Efficacy of E6742, a Dual Antagonist of Toll-Like Receptors 7 and 8, in a First-in-Patient, Randomized, Double-Blind, Phase 1/2 Study in Systemic Lupus Erythematosus","authors":"Yoshiya Tanaka, Atsushi Kumanogoh, Tatsuya Atsumi, Tomonori Ishii, Fumitoshi Tago, Mari Aoki, Shintaro Yamamuro, Shizuo Akira","doi":"10.1101/2024.04.26.24306410","DOIUrl":"https://doi.org/10.1101/2024.04.26.24306410","url":null,"abstract":"<strong>Objectives</strong> To evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response, and efficacy of E6742 in a phase 1/2 study in patients with systemic lupus erythematosus (SLE).","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}