tbuckley/cabot-search huggingface dataset:
AB1117 EXPLORING GENETIC AND IMMUNE CELL DYNAMICS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH EPSTEIN–BARR VIRUS INFECTION VIA COMBINED MICROARRAY AND SINGLE-CELL RNA SEQUENCING ANALYSES
Authors: J. Gui, M. Fang, J. Tu, X. Chen, L. Sun
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Characterized by its clinical diversity and multisystem involvement, Systemic lupus erythematosus (SLE) is a complex autoimmune disease. The development of SLE is determined by a combination of both genetic and environmental factors. It is well documented that Epstein–Barr virus (EBV) infection is closely associated with SLE. However, it remains unclear which genes and immune cells are pivotal in EBV-infected SLE patients. <h3>Objectives:</h3> We aimed to identify overlapping differentially Expressed Genes (DEGs) and immune cell dynamics in both patients with SLE and patients with EBV infection using array data. Subsequently, we aim to further analyze and verify the results of our single-cell sequencing studies. <h3>Methods:</h3> The public microarray data sets of SLE (GSE50772 and GSE81622) or EBV infection (GSE85599 and GSE45918) were obtained from the Gene Expression Omnibus (GEO) database. Subsequently, we conducted differential gene expression analysis to identify overlapping DEGs and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was carried out based on the overlapping DEGs. Subsequently, machine learning approaches were applied to identify key genes from the overlapping DEGs. Finally, we conducted single cell RNA-sequencing in PBMCs isolated from EBV positive SLE patients (SLE-EBV+), EBV negative SLE patients (SLE-EBV-) and normal controls. <h3>Results:</h3> In total, 58 overlapping DEGs were identified, comprising 23 up-regulated genes and 35 down-regulated genes. The most significantly enriched pathways were recognized as oocyte meiosis and circadian rhythm. In addition, we employed machine learning algorithms to select 5 genes (IFI27, TXK, RAPGEF6, PIK3IP1, PSENEN) as key genes (Figure 1). The proportion of T cells CD4 memory resting was significantly decreased in both the SLE database and the EBV infection database. In our scRNA-seq data, the expression of IFI27 was significantly different in all CD4 T cell subsets between SLE-EBV+ and SLE-EBV- patients (Figure 2). Significant differences were observed in the expression of the other four genes (TXK, RAPGEF6, PIK3IP1, PSENEN) in CD8 T cells between SLE-EBV+ and SLE-EBV- patients. TXK, RAPGEF6, and PIK3IP1 also exhibited significant differences in monocytes between SLE-EBV+ patients and EBV- patients. <h3>Conclusion:</h3> The identification of five key genes (IFI27, TXK, RAPGEF6, PIK3IP1, and PSENEN) suggests their potential involvement in the pathogenesis of SLE associated with EBV infection. Notably, IFI27 is considered the most important gene among them. Additionally, our findings suggest that CD4+ T cells, CD8+ T cells, and monocytes may serve as key effector cells playing a vital role in SLE patients infected with the EBV. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0109 EPIDEMIOLOGY, RISK FACTORS, AND IMPACT ON SURVIVAL RATES OF PSYCHIATRIC COMORBIDITIES IN SYSTEMIC SCLEROSIS PATIENTS: A NATIONWIDE POPULATION-BASED COHORT STUDY
Authors: P. Y. Shen, Y. T. Lee, F. Y. Wu, Y. S. Chang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic sclerosis (SSc) is a persistent and incapacitating connective tissue ailment that imposes substantial psychological challenges on individuals. There were few studies with relatively small sample sizes noted a higher risk of psychiatric disorders in SSc patients. <h3>Objectives:</h3> This study analyzed the nationwide database in Taiwan to investigate the epidemiology of psychiatric comorbidities and their impact on survival in patients with SSc. <h3>Methods:</h3> This study enrolled patients diagnosed with systemic sclerosis (SSc) from the National Health Insurance Research Database (NHIRD). These SSc patients were matched with non-SSc controls in a 1:4 ratio based on age and gender. Our study involved a comparison of the incidence rate ratios (IRRs) for new psychiatric disorder diagnoses between the SSc group and the control group. Additionally, a Cox multivariate proportional hazards model was applied to scrutinize the risk factors associated with the development of psychiatric disorders in SSc patients, and the survival was compared between SSc patients with and without psychiatric diseases. <h3>Results:</h3> This study recruited a total of 16,350 participants, consisting of 3,270 patients diagnosed with SSc and 13,080 age- and sex-matched non-SSc controls. SSc patients exhibited a significantly higher risk of psychiatric comorbidities compared to the control group (IRR=1.66, p &lt; 0.001). Within the SSc cohort, the use of oral daily steroid doses ≥ 7.5mg (HR=1.71, p=0.010), intravenous steroid pulse therapy (HR=2.34, p&lt;0.0042), and D-penicillamine (HR=1.60, p &lt; 0.001) were significant risk factors for psychiatric comorbidities (Table 1). Furthermore, SSc patients with psychiatric comorbidities demonstrated significantly lower survival rates compared to those without (Figure 1). <h3>Conclusion:</h3> Individuals diagnosed with SSc had an significantly higer risk of developing psychiatric comorbidities, which, in turn, can adversely affect their survival rates. The identified risk factors for psychiatric comorbidities in SSc included the use of a daily oral steroid dose equal to or exceeding 7.5mg, undergoing steroid pulse therapy, and the administration of D-penicillamine. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1136 INCREASE OF IL10 AND IFNA2 ARE ASSOCIATED TO CLINICAL ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOUS PATIENTS
Authors: E. Grau García, C. Riesco Barcena, A. V. Huaylla Quispe, L. Mas Sanchez, P. Muñoz Martínez, D. Ramos Castro, A. M. Torrat Noves, I. Alcántara Álvarez, B. Villanueva Mañes, H. Charia, M. De la Rubia Navarro, L. Gonzalez Puig, J. Ivorra Cortés, S. Leal Rodriguez, I. Martínez Cordellat, R. Negueroles Albuixech, J. E. Oller Rodríguez, E. Tovar Sugrañes, E. Vicens Bernabeu, I. Cánovas Olmos, C. Nájera Herranz, J. A. Román Ivorra
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic lupus erythematous (SLE) is an autoimmune disease characterized by deregulation of cytokine production. Interferon (IFN) is a proinflamatory cytokine considered as a key molecule in the SLE etiopathogenesis, being responsible of the differentiation of dendritic cells from monocytes, and indirectly of IL10 upregulation. <h3>Objectives:</h3> We aimed to analyze the association between inflammatory cytoquine levels (IFN-a2, IFN-b, IFN-g and IL10) and SLE clinical activity for a follow-up period of 12 months in SLE patients. <h3>Methods:</h3> A longitudinal, observational prospective study with evaluations at baseline and follow-up visits every 3 months (for 1 year) in SLE patients (SLICC 2012 criteria) was performed. In all cases complete laboratory test, clinical evaluation and SLEDAI score was carried out. We analyzed inflammatory cytokines serum levels by colorimetric methods. <h3>Results:</h3> 45 SLE patients (86.7% female) participated in the study, with a mean age at diagnosis of 32.8 (16.2) years and a mean time of disease evolution of 17.9 (11.4) years. The 28.9% of patients showed SLEDAI&gt;6 at the basal visit. The 66.7% of patients were under glucocorticoid treatment, 44.4% under immunosupressants (methotrexate, azatioprine, belimumab or mycophenolate) and 66.7% under antimalarials. SLEDAI and inflammatory cytoquine levels during follow-up is shown in Table 1. Regarding to clinical activity biomarkers, we observed an association between high levels of antidsDNA and elevated IFN-beta (P=0.005) and IFN-gamma (P=0.038), and low levels of C3 and an increment in IL-10 (P=0.006). Patients under antimalarials treatment during follow-up exhibit low levels of IL-10 (P=0.012). No influence of age at diagnosis, time of evolution, vitamin D levels, corticoids and tobacco use in cytoquine levels was observed. <h3>Conclusion:</h3> We observed an association between IL-10, IFN-alpha2, IFN-beta and IFN-gamma levels with clinical activity, independently of the time of follow-up. IL-10 levels may also be influenced by antimalarial treatment. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0781 DYNAMICS OF SERUM LEVELS OF TNF-Α AND IL-6 IN A LONGITUDINAL FOLLOW-UP STUDY IN 101 PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS TREATED WITH BIOLOGIC DRUGS
Authors: N. Morozova, M. Zajc Avramovič, Š. Blazina, G. Markelj, N. Toplak, T. Avčin
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Several studies have investigated levels of serum TNF-α and IL-6 in patients with juvenile idiopathic arthritis (JIA) with active disease compared to those with inactive disease and healthy controls. However, there is limited information concerning the influence of biological drugs on the serum concentrations of TNF-α and IL-6 during treatment. <h3>Objectives:</h3> To determine the dynamics of serum levels of TNF-α and IL-6 in patients with JIA treated with biologic drugs at different time points during treatment and investigate their association with the disease activity. <h3>Methods:</h3> We conducted a single-center, bidirectional, observational cohort study in 101 patients with JIA (32 boys, 69 girls, mean age 13.8 years, mean disease duration 7.2 years) treated with biologic drugs. Disease activity was measured by the Juvenile Arthritis Disease Activity Score including 10 joints (JADAS10) and calculated at each patient visit. Clinical examinations and laboratory assessments of serum levels of TNF-α and IL-6 were performed at baseline before starting therapy with biologic drug and in 6 month intervals afterwards up to 2.5 years. Patients in the retrospective group had additional measurements at various longer time intervals up to 10 years after the start of the biologic therapy. <h3>Results:</h3> Baseline level of TNF-α before therapy with etanercept or adalimumab was significantly lower than the levels of TNF-α at the 1st and 2nd follow-up measurements during the therapy. The analysis of serum levels of TNF-α in relation to the disease activity states showed the highest mean serum levels of TNF-α in patients on etanercept who had low disease activity state and in patients on adalimumab who had inactive disease. In contrast, the highest mean serum level of IL-6 in patients on tocilizumab was observed in patients with active disease state. The correlation analysis in the total cohort of patients with JIA treated with etanercept or adalimumab showed a weak negative correlation between the serum levels of TNF-α and JADAS10 scores (p=0.007), (r=-0.177). In patients with JIA treated with tocilizumab the correlation analysis between the serum levels of IL-6 and JADAS10 scores revealed a positive correlation (p=0.006), (r=0.448). <h3>Conclusion:</h3> The assessment of serum levels of TNF-α in children with JIA during treatment with etanercept or adalimumab is not reliable biomarker of disease activity or immunological remission. In contrast, the serum level of IL-6 in patients with JIA treated with tocilizumab shows positive correlation with disease activity. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1126 REBAMIPIDE ATTENUATES RENAL MANIFESTATIONS VIA ANTIOXIDANT EFFECTS ON PODOCYTES IN AN ANIMAL MODEL FOR SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Y. Park, Y. S. Song, D. S. Kim, S. G. Jang, S. K. Kwok
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rebamipide is a widely used gastroprotective agent. Beyond its muco-protective effects, this agent presented immune-modulatory effects for various rheumatologic diseases such as rheumatoid arthritis, osteoarthritis, Sjogren's syndrome, and Behcet's disease in multiple pre-clinical and clinical studies. However, its efficacies on lupus have not been evaluated yet. <h3>Objectives:</h3> Here, we determined the therapeutic potentials of rebamipide in lupus animal models and suggested possible mechanisms. <h3>Methods:</h3> We administered rebamipide (5 mg/kg) or vehicles in 8-week-old MRL/lpr mice by daily oral feeding for 8 weeks and determined therapeutic efficacies on lupus-like phenotypes and immune cell profiles using their sera and tissues. Through in vitro experiments using immune cells and podocytes acquired from mice, and podocyte cell lines, potential therapeutic mechanisms were evaluated. <h3>Results:</h3> Oral rebamipide administration in lupus-prone mice significantly reduced proteinuria and pathologic scores in renal tissues with increased expression of podocyte-related proteins such as nephrin, synaptopodin, and podocin. Sizes of spleen tissues were significantly more decreased in mice treated with rebamipide than those treated with vehicles. Rebamipide increased the proportion of circulating regulatory T cells in lupus-like mice. In contrast, other immune cell populations such as double negative T cells, CD4+ T cells, CD8+ T cells, and plasma cells were not changed by in vivo treatment of rebamipide. In vitro treatment of rebamipide in primary-cultured murine podocytes resulted in increased expression of structural proteins of podocytes including synaptopodin and podocin, as well as heme oxygenase-1, which is one of the anti-oxidant proteins. These results were replicated in experiments using human and murine podocyte cell lines. <h3>Conclusion:</h3> Rebamipide could be considered as one of the adjunctive treatment options in managing renal manifestations in lupus according to the present results from lupus-prone mice. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number: 2022R1I1A1A01068210). <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1470-HPR PULMONARY FUNCTIONS AND RESPIRATORY MUSCLE STRENGTH IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS
Authors: D. Bayraktar, D. C. Saraç, İ. İnanc, E. Başkan, E. Ugur, A. Özkan, S. Gucenmez, D. Solmaz, S. Akar
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Axial spondyloarthritis (axSpA) is a chronic, auto-inflammatory condition that primarily affects the axial skeleton. Inflammation/ankylosis of thoracic, costovertebral, and costosternal joints contributes to impaired pulmonary functions characterized generally by a restrictive pattern [1]. However, the possible changes in respiratory muscle strength have not been thoroughly explored previously in patients with axSpA. <h3>Objectives:</h3> This study aimed to compare the pulmonary function test and respiratory muscle strength measurement outcomes between axSpA patients and healthy controls. <h3>Methods:</h3> Sixty-two patients with axSpA (33 male) and 52 age, sex, and BMI matched apparently healthy controls (25 male) were included in the study. Physical characteristics and smoking habits were recorded in both groups. Disease-related data (time passed since diagnosis and onset of the symptoms, disease activity) were inquired in axSpA group. Pulmonary functions and respiratory muscle strengths were evaluated by using a portable device (Cosmed Pony FX, Rome, Italy). Pulmonary function testing included measurements of forced vital capacity (FVC), forced expiratory volume in the 1<sup>st</sup> second (FEV<sub>1</sub>), and FEV<sub>1</sub>/FVC ratios. Maximal inspiratory (PI<sub>max</sub>) and expiratory (PE<sub>max</sub>) mouth pressure measurements were used for determining respiratory muscle strength. Dyspnea perceptions were assessed using modified Medical Research Council Dyspnea Score. <h3>Results:</h3> Group characteristics are presented at Table 1. Groups were similar regarding physical characteristics and smoking status (p&gt;0.05). Dyspnea perception was higher in axSpA group (p&lt;0.001). FVC (p=0.03) and FEV<sub>1</sub> (p=0.009) were also lower in axSpA group compared to healthy controls. No between group differences were observed in terms of FEV<sub>1</sub>/FVC ratios, PI<sub>max</sub>, and PE<sub>max</sub> outcomes (p&gt;0.05). <h3>Conclusion:</h3> Patients with axSpA present higher dyspnea perception and diminished pulmonary functions compatible with restrictive pulmonary pattern compared to their healthy peers. However, respiratory muscle strength seems to be preserved in these patients. <h3>REFERENCES:</h3> [1] Berdal G, Halvorsen S, van der Heijde D, Mowe M, Dagfinrud H. Restrictive pulmonary function is more prevalent in patients with ankylosing spondylitis than in matched population controls and is associated with impaired spinal mobility: a comparative study. Arthritis Res Ther. 2012;14(1): R19. <h3>Acknowledgements:</h3> The present study was supported by the Scientific and Technological Research Council of Türkiye (TUBITAK) within the scope of the 2209-National/International Research Projects Fellowship Program for Undergraduate Students 2022/2 with grant number 1919B012218802. <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1137 BODY COMPOSITION STATUS IN SLE PATIENTS AND ITS ASSOCIATIONS WITH FUNCTIONAL PERFORMANCE AND QUALITY OF LIFE: A CASE-CONTROL STUDY
Authors: Y. Seheda, S. Shevchuk, I. Kuvikova, A. Boienko, S. Seheda
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> It is well known that SLE is the autoimmune disorders with predominate musculoskeletal injuries such as arthritis, myositis etc. which could affect patients physical activity and life quality. Therefore, the real state of body composition state in SLE patients and its impact on functional activity and life quality is still unclear. <h3>Objectives:</h3> The aim of this study was to evaluate body composition status of SLE patients compared to healthy controls and to investigate its association with physical performance and life quality. <h3>Methods:</h3> This cross-sectional study includes 31 women with SLE of mean age 45,3<b>±</b>7,0 years with mean disease duration 9,7<b>±</b>4,6 years and 29 healthy age and sex-matched subjects. Body composition status (fat mass total/lean mass total/appendicular skeletal muscle mass (ASSM)/appendicular skeletal muscle index (ASMI) was mesaured by dual-energy X-ray absorbtiometry (DXA). Muscle function was evaluated by grip strength with handheld-dynamometer and by chair stand test. Life quality was measured by HAQ and SF-36 questionnaires in both groups. The Asian Working Group criteria on Sarcopenia (2019) were used as cut-off point for low muscle strength, muscle mass and physical performance. Statistical analysis was conducted with a t-test for mean difference, and linear regression was used to adjust confounders. <h3>Results:</h3> The SLE patients showed significantly differences in all body composition measurments compared to healthy control group. Thus the mean lean mass total/ASSM/ASMI were significantly lower in SLE group than in healthy controls (46403,02<b>±</b>2533,5gram vs 52856,6<b>±</b>45435.8gram (p&lt;0.001), 19605,4<b>±</b>1199,3 gram vs 24745,2<b>±</b>2389,7gram (p&lt;0.005) and 6,07±0,57 vs 8,26±0,93 (p&lt;0.005) while the fat mass was not signicantly different in both group (26833,2<b>±</b>4072,5 gram vs 27943,6<b>±</b>3074,9 gram). The muscle function of SLE patients was also significantly lower than in control group (21,0 <b>±</b>8,7 kg vs 30,6<b>±</b>9,3 kg by grip strength and 7,4<b>±</b>1,5 sec. vs 12,7<b>±</b>1,3 sec. by chair test p&lt;0.005) The SLE patients also demonstrated poorer quality of life evaluated by HAQ and SF-36 questionnaires compared to healthy controls (p&lt;0.005). In addition, deviation in body composition such as low ASSM and ASMI were directly associated with limited functional performance and lower life quality in SLE patients (p&lt;0.001). <h3>Conclusion:</h3> SLE patients showed significant disproportion in body composition compared to general population. Lower ASSM and ASMI are the predictors of limited physical activity and poorer life quality of patients with SLE. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
OP0002-PARE A LARGE LANGUAGE MODEL BASED APPROACH TO PROVIDING PERSONALISED HEALTH-RELATED INFORMATION FOR OSTEOPOROSIS PATIENTS
Authors: A. Wilson, A. Adesina, Y. Jiao, K. Douglas
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The Internet has long been recognised as a medium that patients use to gather information about their medical conditions [1]. The wealth of information it contains and uncertainty about its credibility can lead to the lack of personalisation for the patient, resulting in time consuming searches for the information that the patient wants. <h3>Objectives:</h3> In order to improve patient information management this project created a mobile device-based large language model (LLM) chat-bot that could provide non-pharmacological and generalised recommendations for people living with osteoporosis. <h3>Methods:</h3> The system implements Retrieval Augmented Generation (RAG) pattern and consists of the following foundational components: a chat-bot interface designed to interact with users; a gpt-3.5-turbo LLM chain with generative question-answering (G-Q-A) capabilities; a database to store vector embeddings; a retriever using maximum marginal relevance (MMR) algorithm to query the vector embeddings. All information was derived from clinically approved sources including Royal Osteoporosis Society, National Osteoporosis Society, National Osteoporosis Guideline Group, UK, International Osteoporosis Foundation (IOF) and National Osteoporosis Foundation. The system runs on Android mobile devices. The system was evaluated based upon technical metrics (correct responses to 97 pre-generated question-and-answer pairs), its ability to handle unethical questions or questions outside the defined domain as well as for overall usability (System Usability Scale questionnaire [SUS]) which rates usability on a scale of 0 (poor) to 100 (excellent). The latter was done with the help of general users who were healthy volunteers age range:18-24 (n:1); 25-34 (n:17); 35-44(n:1) and 55+ (n:1) as as well as medical professionals (n:4). <h3>Results:</h3> Evaluation revealed that gpt-3.5-turbo scored 96% for predicting correct answers on the evaluation dataset of questions. Unethical and non-domain specific questions were correctly filtered out. Usability was scored as excellent by both medical professionals (83±11.6) and general users (85±12.9). <h3>Conclusion:</h3> With growing and fast pace advances in artificial intelligence the authors have demonstrated that LLM-Chatbots can be used to manage large amounts of health-related information in a reliable way. It has the potential to provide personalise information to patient queries using an easy to use computer-based question and answering system. Further evaluations will be needed with the help of osteoporosis patients in order to further refine it. <h3>REFERENCES:</h3> [1] Wilson AS, Kitas GD, Lewellyn P, Carruthers DM, Cheseldine DC, Harris S, Bacon PA, Huisson AP and Young SP (2001). Provision of Internet Based Rheumatology Education. Rheumatology 40(6): 645-51. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>