ACR open rheumatology最新文献

{"title":"The Relationship Between Anti-Cell Division Cycle and Apoptosis Regulator 1 Autoantibodies, Anti-Sp4 Autoantibodies, and Cancer in Anti-Transcription Intermediary Factor 1γ-Positive Dermatomyositis.","authors":"Christopher A Mecoli, David Fiorentino, Jemima Albayda, Julie J Paik, Eleni Tiniakou, Brittany Adler, Andrew L Mammen, Lisa Christopher-Stine, Antony Rosen, Livia Casciola-Rosen","doi":"10.1002/acr2.11750","DOIUrl":"10.1002/acr2.11750","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to describe the frequency, co-occurrence, and cancer association of anti-cell division cycle and apoptosis regulator 1 (anti-CCAR1) and anti-Sp4 in two large independent adult dermatomyositis (DM) cohorts.</p><p><strong>Methods: </strong>Anti-transcription intermediary factor 1γ (anti-TIF1γ)-positive patients with DM from two independent cohorts were studied to determine the serologic overlap of anti-CCAR1 and anti-Sp4 autoantibodies measured by enzyme-linked immunosorbent assay. Associations between cancer-associated myositis (CAM) and antibody-defined subgroups within anti-TIF1γ-positive patients with DM were determined.</p><p><strong>Results: </strong>A total of 305 anti-TIF1γ-positive patients with DM were studied: 169 patients from Johns Hopkins and 136 patients from Stanford. In each cohort, approximately one-third of anti-TIF1γ-positive patients with DM were anti-Sp4 positive, one-third were anti-CCAR1 positive, 20% were positive for both, and half of patients were negative for both. There was a strong association with CAM in patients lacking both these antibodies (Johns Hopkins, odds ratio [OR] 12.9 [95% confidence interval (CI) 3.6-89.5]; Stanford, OR 4.5 [95% CI 1.8-13.2]). The strongest negative association with CAM was found in patients with anti-Sp4 or anti-CCAR1 (Johns Hopkins, OR 0.07 [95% CI 0.01-0.27]; Stanford, OR 0.22 [95% CI 0.07-0.55]).</p><p><strong>Conclusion: </strong>Both anti-Sp4 and anti-CCAR1 autoantibody subgroups are negatively associated with CAM. Although the magnitude of this association is substantial, cancer occasionally occurs in patients positive for either specificity. Conversely, approximately half of anti-TIF1γ-positive patients with DM are negative for both antibodies (anti-Sp4/anti-CCAR1 negative), and thus this subgroup may warrant more intensive cancer surveillance.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"912-917"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Preclinical Murine Model of Systemic Lupus Erythematosus-Like Cardiovascular Disease.","authors":"Marice K McCrorey, Kennedy P Hawkins, Marharyta Semenikhina, Matthew Bernstein, Ryan Lacey, C Alex Colvert, Jim C Oates, Betty P Tsao, Kristine Y DeLeon-Pennell, Oleg Palygin, Melissa A Cunningham, Justin P Van Beusecum","doi":"10.1002/acr2.11744","DOIUrl":"10.1002/acr2.11744","url":null,"abstract":"<p><strong>Objective: </strong>Systemic lupus erythematosus (SLE) affects nine women to every man worldwide, and these patients are at greater risk for cardiovascular disease (CVD) morbidity and mortality. Clinical studies have demonstrated that patients with SLE are more likely to develop CVD, including cardiac and vascular dysfunction. Although many preclinical models of SLE are available, including treatment with Toll-like receptor (TLR) 7/8 agonists, a consistent preclinical model of SLE-like CVD with systemic, cardiac, renal, and cerebral endothelial activation and cardiac dysfunction has yet to be described. Here, we hypothesize that acceleration of SLE with the TLR7/8 agonist resiquimod (R848) will promote cardiac and endothelial activation with subsequent end-stage organ damage in the SLE-prone B6.Nba2 mouse model.</p><p><strong>Methods: </strong>Female and male SLE-prone B6.Nba2 mice were treated with R848 or acetone, administered topically twice weekly over a four-week period, to accelerate the development of SLE-like pathophysiology. Echocardiography was performed at baseline, 4 weeks, and 16 weeks. At 16 weeks, tissues were harvested, weighed, and analyzed by histology, immunofluorescence, real-time quantitative polymerase chain reaction, and enzyme-linked immunosorbent assays.</p><p><strong>Results: </strong>We found that female R848-treated mice had increased serum anti-Smith and immunoglobulin G complex deposition in the kidney, heart, and brain consistent with SLE-like etiology. Tissue analysis revealed significant enlargement of the spleen in both female and male R848-treated mice, with only cardiac and renal enlargement in females compared to their respective controls. Echocardiographic imaging revealed left ventricular wall thickening by 4 weeks that was followed by a progressive increase in left ventricular internal diameters and subsequent decrease in ejection fraction over the 16-week time course in female mice. We found that circulating levels of soluble vascular adhesion molecule-1 and soluble intracellular adhesion molecule-1 were increased in both female and male R848-treated mice, whereas cardiac and renal fibrosis were significantly increased in only female R848-treated mice.</p><p><strong>Conclusion: </strong>Our data demonstrate that R848 treatment of SLE-prone B6.Nba2 mice is a novel preclinical model to study the sex-dependent pathophysiologic mechanisms of SLE-like CVD.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"891-899"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic JAK1 Inhibition Reverses Lupus Nephritis in a Mouse Model and Demonstrates Transcriptional Changes Consistent With Human Disease.","authors":"Rachel E Twomey, Stuart J Perper, Susan V Westmoreland, Swetha Srinivasan, Suzanne L Mathieu, Kristine E Frank, Jozsef Karman, Andrew J Long, William J Housley, Stephen H Clarke","doi":"10.1002/acr2.11745","DOIUrl":"10.1002/acr2.11745","url":null,"abstract":"<p><strong>Objective: </strong>Janus kinase family members are essential for signaling by multiple cytokines, including many implicated in systemic lupus erythematosus (SLE) pathogenesis. To test whether inhibition of JAK1 signaling can be efficacious in SLE, we used a JAK1-selective inhibitor (ABT-317) and evaluated its ability to ameliorate disease in murine SLE.</p><p><strong>Methods: </strong>Efficacy of ABT-317 was evaluated using NZB/W-F₁ mice treated prophylactically and therapeutically. Primary endpoints were proteinuria, survival, and saliva production. Other endpoints included histological analysis of kidneys and salivary glands, flow cytometric analysis of splenic cell populations, and gene expression analysis by RNA sequencing in the kidneys, salivary glands, and blood. Publicly available human kidney gene transcription data were used to assess the translatability of the mouse findings.</p><p><strong>Results: </strong>ABT-317 was efficacious when dosed prophylactically and prevented disease for up to two months after treatment cessation. When dosed therapeutically, ABT-317 quickly reversed severe proteinuria and restored saliva production, as well as diminished kidney and salivary gland inflammation. ABT-317-induced changes in glomerular morphology coincided with normalization of a human nephrotic gene signature, suggesting translatability to human lupus nephritis (LN).</p><p><strong>Conclusion: </strong>JAK1 inhibition prevented and reversed kidney and salivary gland manifestations of murine lupus with long-lasting effects after treatment cessation. These data, along with the presence of JAK1 and nephrotic gene signatures in human LN glomeruli, suggest that a JAK1-selective inhibitor may be an effective therapeutic in the treatment of human SLE and LN.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"900-911"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspectives of Rheumatologists on the Type 1 and 2 Systemic Lupus Erythematosus Model.","authors":"Amanda M Eudy, Megan E B Clowse, Amy Corneli, Summer Starling, Nneka Jebose Molokwu, Teresa Swezey, David S Pisetsky, Mithu Maheswaranathan, Jayanth Doss, Kai Sun, Rebecca E Sadun, Lisa G Criscione-Schreiber, Jennifer L Rogers","doi":"10.1002/acr2.11748","DOIUrl":"10.1002/acr2.11748","url":null,"abstract":"<p><strong>Objective: </strong>The Type 1 and 2 systemic lupus erythematosus (SLE) Model was developed to encapsulate all signs and symptoms that patients with SLE experience. Our previous qualitative work demonstrated the model accurately reflects the lived experience of people living with SLE. The objective of this study was to present the Type 1 and 2 SLE Model to rheumatologists to understand how the model fits with their experiences treating patients with SLE.</p><p><strong>Methods: </strong>We conducted a qualitative descriptive study using semistructured interviews with rheumatologists. Rheumatologists were asked about their general impression of the Type 1 and 2 SLE Model, how the model does or does not fit within their approach to treating patients with SLE, the utility of the model in clinical practice, and any suggested changes. Applied thematic analysis identified salient themes.</p><p><strong>Results: </strong>We interviewed 13 rheumatologists. The majority of rheumatologists approved of the model and found it useful to guide therapy and clinical decision-making. Several rheumatologists thought the model was helpful for patient education to manage expectations about differences between Type 1 and Type 2 symptoms and treatments. A few rheumatologists expressed concern that the model could lead to an overdiagnosis of SLE.</p><p><strong>Conclusion: </strong>The Type 1 and 2 SLE Model was accepted by most rheumatologists interviewed and welcomed as a useful approach to identifying and treating symptoms in patients with SLE. Future studies will determine how implementing the Type 1 and 2 SLE Model affects patient understanding, the physician-patient relationship, and clinical outcomes.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"865-870"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Limited Health Literacy With Clinical and Patient-Reported Outcomes in Individuals With Systemic Lupus Erythematosus.","authors":"Mithu Maheswaranathan, Andrea D Boan, Viswanathan Ramakrishnan, Hetlena Johnson, Jillian Rose, Clara L Dismuke-Greer, Jim C Oates, Leonard E Egede, Edith Williams","doi":"10.1002/acr2.11719","DOIUrl":"10.1002/acr2.11719","url":null,"abstract":"<p><strong>Objective: </strong>Health literacy is an important social determinant of health, with limited health literacy associated with worse health outcomes. This study examined the associations between limited health literacy with patient-reported outcomes and disease activity/damage among 267 Black women with active systemic lupus erythematosus (SLE) enrolled in the Peer Approaches to Lupus Self-Management (PALS) program.</p><p><strong>Methods: </strong>The three-item Chew Health Literacy Screening was used to dichotomize those reporting in the \"limited\" range on any item with outcomes compared via generalized linear models. Baseline surveys and assessments obtained at study entry as part of the PALS study were used. Primary outcomes included disease activity and lupus damage; other secondary outcomes included patient activation, self-efficacy, physician/patient communication, and quality of life.</p><p><strong>Results: </strong>The study included 267 Black women with SLE. In covariate-adjusted analyses, participants with limited health literacy (88 [33%]) were more likely to have lower patient activation (Patient Activation Measure P < 0.0001), lower self-efficacy (Lupus Self-Efficacy P < 0.0001), higher lupus damage (self-administered Brief Index of Lupus Damage P = .016), higher disease activity (Systemic Lupus Activity Questionnaire symptom severity P = 0.006), and worse physician/patient communication (patient-centered care P < 0.0001) compared to those with adequate health literacy. Those with limited health literacy also reported worse lupus quality of life (P = 0.0004) and greater levels of stress (Perceived Stress Scale-4 P < 0.0001) and were 2.4 times more likely to have probable major depression (Patient Health Questionnaire Depression Scale-8 of ≥10 P = 0.004) and probable anxiety disorder (General Anxiety Disorder-7 of ≥10 P = 0.007) compared to those with adequate health literacy.</p><p><strong>Conclusion: </strong>Black women with SLE and limited health literacy have worse clinical outcomes and represent a particularly vulnerable population with significantly disparate health outcomes. These findings suggest health literacy and complexities of managing SLE may impair clinical care in multiple domains, ultimately contributing to higher disease activity and death/damage, and are important to address in clinical care and future interventions in patients with SLE.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"780-789"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease Phenotypes in Refractory Musculoskeletal Pain Syndromes Identified by Unsupervised Machine Learning.","authors":"Thomas Hügle, Tiffany Prétat, Marc Suter, Chris Lovejoy, Pedro Ming Azevedo","doi":"10.1002/acr2.11699","DOIUrl":"10.1002/acr2.11699","url":null,"abstract":"<p><strong>Objective: </strong>Overlapping chronic pain syndromes, including fibromyalgia, are heterogeneous and often treatment-resistant entities carrying significant socioeconomic burdens. Individualized treatment approaches from both a somatic and psychological side are necessary to improve patient care. The objective of this study was to identify and visualize patient clusters in refractory musculoskeletal pain syndromes through an extensive set of clinical variables, including immunologic, psychosomatic, wearable, and sleep biomarkers.</p><p><strong>Methods: </strong>Data were collected during a multimodal pain program involving 202 patients. Seventy-eight percent of the patients fulfilled the criteria for fibromyalgia, 77% had a concomitant psychiatric-mediated disorder, and 22% a concomitant rheumatic immune-mediated disorder. Five patient phenotypes were identified by hierarchical agglomerative clustering as a form of unsupervised learning, and a predictive model for the Brief Pain Inventory (BPI) response was generated. Based on the clustering data, digital personas were created with DALL-E (OpenAI).</p><p><strong>Results: </strong>The most relevant distinguishing factors among clusters were living alone, body mass index, peripheral joint pain, alexithymia, psychiatric comorbidity, childhood pain, neuroleptic or benzodiazepine medication, and response to virtual reality. Having an immune-mediated disorder was not discriminatory. Three of five clusters responded to the multimodal treatment in terms of pain (BPI intensity), one cluster responded in terms of functional improvement (BPI interference), and one cluster notably responded to the virtual reality intervention. The independent predictive model confirmed strong opioids, trazodone, neuroleptic treatment, and living alone as the most important negative predictive factors for reduced pain after the program.</p><p><strong>Conclusion: </strong>Our model identified and visualized clinically relevant chronic musculoskeletal pain subtypes and predicted their response to multimodal treatment. Such digital personas and avatars may play a future role in the design of personalized therapeutic modalities and clinical trials.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"790-798"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embracing preprints in rheumatology: accelerating knowledge dissemination, career development, and collaborative opportunities.","authors":"Amr H Sawalha","doi":"10.1002/acr2.11720","DOIUrl":"10.1002/acr2.11720","url":null,"abstract":"","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"734-735"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Bimekizumab in Patients With Psoriatic Arthritis With or Without Methotrexate: 52-Week Results From Two Phase 3 Studies.","authors":"Iain B McInnes, Philip J Mease, Yoshiya Tanaka, Laure Gossec, M Elaine Husni, Lars Erik Kristensen, Richard B Warren, Barbara Ink, Rajan Bajracharya, Jason Coarse, Alice B Gottlieb","doi":"10.1002/acr2.11727","DOIUrl":"10.1002/acr2.11727","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to assess 52-week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/-MTX) treatment at baseline.</p><p><strong>Methods: </strong>We conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi-IR]), and the BE VITAL open-label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo-randomized patients received bimekizumab. Missing data were imputed using non-responder imputation, multiple imputation, or worst-category imputation.</p><p><strong>Results: </strong>Through Week 52, similar proportions of bimekizumab-treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and -MTX (BE OPTIMAL: 54.4% +MTX, 54.7% -MTX; BE COMPLETE: 56.3% +MTX, 48.0% -MTX). Similar proportions of bimekizumab-treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and -MTX groups. Similar trends were seen in placebo/bimekizumab-treated patients. Through Week 52, the proportion of bimekizumab-treated patients with ≥1 treatment-emergent adverse event were similar between the +MTX and -MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab.</p><p><strong>Conclusion: </strong>Treatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD-naïve and TNFi-IR patients with PsA and was well tolerated, irrespective of concomitant MTX.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"720-731"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversity and Inclusivity in Rheumatology Publications.","authors":"Amr H Sawalha, Kelli D Allen, Candace H Feldman, S Sam Lim, Andras Perl, Daniel H Solomon, Edith M Williams","doi":"10.1002/acr2.11721","DOIUrl":"10.1002/acr2.11721","url":null,"abstract":"","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"732-733"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Specific Transposable Element and Gene Expression Analysis Across Systemic Lupus Erythematosus Phenotypes.","authors":"Zachary Cutts, Sarah Patterson, Lenka Maliskova, Kimberly E Taylor, Chun Jimmie Ye, Maria Dall'Era, Jinoos Yazdany, Lindsey A Criswell, Gabriela K Fragiadakis, Charles Langelier, John A Capra, Marina Sirota, Cristina M Lanata","doi":"10.1002/acr2.11713","DOIUrl":"10.1002/acr2.11713","url":null,"abstract":"<p><strong>Objective: </strong>There is an established yet unexplained link between interferon (IFN) and systemic lupus erythematosus (SLE). The expression of sequences derived from transposable elements (TEs) may contribute to SLE phenotypes, specifically production of type I IFNs and generation of autoantibodies.</p><p><strong>Methods: </strong>We profiled cell-sorted RNA-sequencing data (CD4⁺ T cells, CD14⁺ monocytes, CD19⁺ B cells, and natural killer cells) from peripheral blood mononuclear cells of 120 patients with SLE and quantified TE expression identifying 27,135 TEs. We tested for differential TE expression across 10 SLE phenotypes, including autoantibody production and disease activity.</p><p><strong>Results: </strong>We found 731 differentially expressed (DE) TEs across all SLE phenotypes that were mostly cell specific and phenotype specific. DE TEs were enriched for specific families and open reading frames of viral genes encoded in TE sequences. Increased expression of DE TEs was associated with genes involved in antiviral activity, such as LY6E, ISG15, and TRIM22, and pathways such as IFN signaling.</p><p><strong>Conclusion: </strong>These findings suggest that expression of TEs contributes to activation of SLE-related mechanisms in a cell-specific manner, which can impact disease diagnostics and therapeutics.</p>","PeriodicalId":93845,"journal":{"name":"ACR open rheumatology","volume":" ","pages":"769-779"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}