tbuckley/cabot-search huggingface dataset:
POS0134 SYSTEMIC INFLAMMATORY CYTOKINE PROFILES IN PATIENTS WITH GOUT DURING FLARE, INTERCRITICAL, AND TREAT-TO-TARGET PHASES: TNFSF14 AS NEW BIOMARKER
Authors: H. K. Ea, B. Kischkel, T. W. Chirayath, V. Klück, C. Aparicio, H. U. Loeung, P. Maniver, T. Jansen, M. Zarka, F. Lioté, A. Latourte, T. Bardin, A. Gauffenic, E. Vicaut, T. Crisan, M. Netea, P. Richette, L. Joosten
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Untreated gout is characterized by monosodium urate (MSU) crystal accumulation responsible for recurrent flares that are commonly separated by asymptomatic phases. Both phases are inflammatory conditions of variable intensity. Gout flares are self-limited inflammatory reactions involving multiple mediators. <h3>Objectives:</h3> This study aimed to characterize the inflammatory profiles of gout disease at 3 different phases. <h3>Methods:</h3> Using the Olink targeted proteomics, levels of 92 inflammation-related proteins were measured in plasma samples of a prospective gout population (GOUTROS), collected at the onset of gout flare (T1), the intercritical phase (T2), and after reaching the serum urate target level under urate-lowering therapy (T3). Results were validated in an independent cohort. Ex vivo and in vitro experiments were performed to assess the inflammatory properties of new biomarkers. <h3>Results:</h3> In total, 21 inflammatory new biomarkers were differentially expressed during the 3 gout phases. The levels of 4 of these proteins (interleukin 6 [IL-6], colony-stimulating factor 1, vascular endothelial growth factor A and tumour necrosis factor superfamily 14 [TNFSF14]) were increased during gout flare in an independent cohort. IL-6 and TNFSF14 had the highest fold change in expression during T1 versus T2 or T3. TNFSF14 concentration was higher in synovial fluids collected during gout flare than during osteoarthritis (283.7 ±559.1 vs 10.8 ±31.1 pg/ml, p&lt;0.001). Similarly, TNFSF14 expression was higher in mouse air pouch membranes collected after MSU crystal stimulation than after saline stimulation. These results suggested that TNFSF14 was produced locally at the inflamed joint. In vitro, recombinant TNFSF14 protein enhanced the inflammatory response of human PBMCs exposed to lipopolysaccharide and MSU crystal stimulation. Conversely, TNFSF14 blockade reduced the inflammatory response. Additionally, single nucleotide polymorphisms of <i>TNFSF14</i> affected the ability of myeloid cells to produce inflammatory cytokines. PBMCs collected from individuals carrying rs344559 exhibited decreased production of IL-1β, while PBMCs collected from individuals carrying rs2101765 showed increased production of IL-1β and IL-6. <h3>Conclusion:</h3> This study helps to improve the understanding of how the human immune system reacts in different stages of gout, allowing the identification of TNFSF14 as a new biomarker associated with gout flare. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0690 ASSOCIATION OF RHEUMATOID ARTHRITIS WITH AGE-RELATED MACULAR DEGENERATION: A NATIONWIDE COHORT STUDY
Authors: Y. Eun, J. M. Yoon, K. D. Han, B. S. Kim, W. Jung, H. Kim, D. H. Lim, D. W. Shin
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Previous cohort studies have indicated an increased risk of age-related macular degeneration (AMD) in patients with rheumatoid arthritis. However, the relationship between AMD and RA is still unclear, and data on the risk of RA in AMD patients from Asia remain inadequate. <h3>Objectives:</h3> We sought to assess the association between AMD with/without visual disability and the risk of RA occurrence using National Health Insurance data in South Korea. <h3>Methods:</h3> In total, 3,537,293 individuals who underwent health screening program checkups between January 1, 2009 and December 31, 2009 were included and followed until December 31, 2019. Participants with a visual disability were defined as those with loss of vision or a visual field defect as certified by the Ministry of Health and Welfare of Korea. Using multivariable adjusted Cox regression analysis, RA hazard ratios were estimated for control and AMD with/without visual disability groups. <h3>Results:</h3> In total, 43,772 participants (1.24%) were diagnosed with RA. Individuals with AMD were at higher risk of RA compared to controls, regardless of the presence of visual disability (adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.02–1.21). Among individuals with AMD, different risk levels of RA were observed between those without visual disability (aHR, 1.13; 95% CI, 1.03–1.21) and those with visual disability (aHR, 0.90; 95% CI, 0.64–1.27). <h3>Conclusion:</h3> AMD was associated with a higher risk of RA, which remained significant as a trend even after adjusting for lifestyle factors and comorbidities. Future research is needed to clarify the biological basis for the association between AMD and RA. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0323 GUT COMMENSAL TRANSLOCATION AND MOLECULAR MIMICRY FOR AUTOANTIBODY PRODUCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: M. Katsushima, Y. Nakayama, T. Yoshida, Y. Nishida, M. Shirakashi, R. Nakashima, H. Yoshifuji, R. Watanabe, A. Morinobu, M. Hashimoto
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Bacterial translocation across the gut barrier has been implicated in autoimmune diseases, including systemic lupus erythematosus (SLE). However, it remains unclear how translocated bacteria contribute to the development of autoimmunity. <h3>Objectives:</h3> The present study aimed to elucidate the role of gut commensal translocation in the context of molecular mimicry, by utilizing lupus model mice and blood samples from untreated patients with SLE. <h3>Methods:</h3> We have previously generated C57BL/6 Zap70skg/skg (B6SKG) mice, a lupus model characterized by expanded autoreactive T cells and gut dysbiosis. C57BL/6 (wild-type [WT]) mice were used as controls. All mice were maintained under specific pathogen-free conditions at Kyoto University. Bacterial translocation was evaluated by non-selective culture of mesenteric lymph nodes (MLNs). The pathogenic potency of cultured bacteria and its antigen was investigated by <i>in vivo</i> experiments, ELISA, western blotting and epitope mapping. <h3>Results:</h3> The rates of bacterial translocation were same between B6SKG and WT mice. The profiling of cultured bacteria in MLNs demonstrated that <i>Lactobacillus murinus</i>, known as a gut symbiont in rodents, was enriched in B6SKG mice with increased anti-dsDNA antibody levels. The injection of heat-killed <i>L. murinus</i> replicated the autoantibody production in B6SKG mice. A protein band of <i>L. murinus</i> with cross-reactivity to anti-dsDNA antibodies was analyzed by mass spectrometry, and identified as peptide ATP-binding cassette transporter (ABCT). Recombinant <i>L. murinus</i> ABCT was generated, and its cross-reactivity was confirmed by <i>in-vivo</i> immunization and ELISA inhibition assay. In addition, anti-ABCT antibody levels were significantly correlated with anti-dsDNA antibody levels in B6SKG mice. Notably, SLE patients also showed elevated anti-ABCT antibody levels, and epitope mapping of <i>L. murinus</i> ABCT revealed common binding sites between mice and humans. Part of the binding sequences was predicted as MHC class II-restricted epitopes, and located on the protein's surface in the three-dimensional model structure. <h3>Conclusion:</h3> The translocation of a gut symbiont with its mimicry antigen contributes to lupus autoantibody production. Bacterial translocation and commensal-induced molecular mimicry may play pathogenic roles in hosts predisposed to autoimmunity. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> We would like to sincerely thank all those who have been involved for their valuable contributions. <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0473 DECREASE OF GLOMERULAR FILTRATION RATE AMONG RHEUMATOID ARTHRITIS PATIENTS
Authors: C. L. Giraldo Herrera, W. G. Rojas Zuleta, Y. G. Toloza-Perez, J. H. Donado Gómez, N. Duque Zapata, C. Becerra-Arias
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rheumatoid arthritis (RA) is systemic autoimmune disease that targets the synovial joints and potentially resulting in the permanent destruction of cartilage and bone if not adequately treated. Numerous cohort studies have highlighted an increased risk of chronic kidney disease in RA patients compared to healthy controls. This risk may be influenced by medications and accelerated atherosclerosis due to the increased inflammatory burden. However, data on this risk are not yet well-characterized. <h3>Objectives:</h3> To evaluate the decline of glomerular filtration rate (eGFR) among RA patients during follow up. <h3>Methods:</h3> A cohort study was conducted involving RA patients followed for a minimum of one year in Medicarte SAS, a Colombian center for immune-mediated diseases. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (2), this result was rounded to the nearest whole number. A mixed linear regression model was carried out using the 'lmer' function from the 'lme4' package in R software (3). The model considered the relationship between the dependent variable eGFR, time and other factors including hypertension (HT) and diabetes mellitus (DM). To assess stability, a bootstrap simulation (comprising 1000 iterations) was conducted. Interquartile range (IQR) was calculated for both the simulated and observed values. Finally, the adjusted values were generated and the correlation matrix of the variance-covariance of the random effects was calculated. <h3>Results:</h3> A total 1,971 RA patients were included, with 89.3% (n= 1730) being female. The median age at baseline was 5.4 years (IQR= 2.1-6.8). The median follow-up duration was 5.04 years (IQR= 2.2-6.8). Initially, 20% (n=396) of individuals had HT and 4.2% (n=84) had DM. The statistical model revealed that, on average, in RA patients each unit increase in time was associated with a decrease in eGFR by 0.97 ml/min/1.73m<sup>2</sup>. A Patients with DM showed a significant decrease in eGFR of 2.9. Individuals with HT had a decrease of 6.8, and those with both conditions experienced a reduction in eGFR of 7.5 ml/min/1.73m<sup>2</sup>. The model reports considerable variability among individuals, suggesting personal differences in baseline levels of CKD-EPI, Table 1. <h3>Conclusion:</h3> In our cohort, RA patients exhibited a decline in eGRF by 0.97 ml/min/1.73m<sup>2</sup>, comparable to eGFR decline observed in healthy individuals (4). Notably, RA patients with HT and DM exhibited a more pronounced decline in eGFR, suggesting an elevated risk of chronic kidney disease and associated mortality. Further investigation is warranted to validate these findings. <b>Table 1.</b> Summary of Model <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1239 DEEP LEARNING BASED IMAGE RECOGNITION SYSTEM OF SALIVARY GLAND ULTRASOUND ASSISTED DIAGNOSIS OF PRIMARY SJOGREN ’S SYNDROME
Authors: Z. Zhang, Y. Geng, X. Zhang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Salivary gland ultrasound (SGUS) is a valuable modality for the diagnosis of primary Sjögren's syndrome (pSS). However, the widespread use of it as standardized diagnostic tools is limited by inter/intra operator variability. <h3>Objectives:</h3> The aim of this study was to evaluate the utility of deep learning-based SGUS image recognition system in the diagnosis of pSS. <h3>Methods:</h3> Between June 2022 and Sep 2023, 4017 SGUS images of 678 patients from one center were included in this study. Among them, 259 patients with 1524 images were diagnosed as pSS and 419 patients with 2493 images were non-SS. All the SGUS image data were randomly divided into training dataset (64%), validation dataset (16%) and testing dataset (20%). The SGUS automatic classification model was developed by using a 2D deep residual convolutional network architecture (RESNET-50). The predictive performance was validated by sensitivity, specifcity and area under reciver operating characteristic curve (ROC). <h3>Results:</h3> When applying deep learning-based SGUS assessment, it show similar performance with operator based SGUS score system.The specifcity is similar (89.3% vs. 90.0%), while a little bit lower sensitivity (55.8% vs. 61.4%). The area under the ROC were comparable between them (0.805 vs 0.890). <h3>Conclusion:</h3> Deep learning-based SGUS image recognition system maybe an objective and promising tool compared to expert-based scoring of SGUS in the diagnosis of pSS. This may support SGUS as an effective and prospective diagnostic tool to supplement current diagnostic methods. <h3>REFERENCES:</h3> [1] Olivier A, Hoffmann C, Jousse-Joulin S, Mansour A, Bressollette L, Clement B. Machine and Deep Learning Approaches Applied to Classify Gougerot-Sjögren Syndrome and Jointly Segment Salivary Glands. Bioengineering (Basel). 2023 Nov 3;10(11):1283. [2] Vukicevic AM, Radovic M, Zabotti A, Milic V, Hocevar A, Callegher SZ, De Lucia O, De Vita S, Filipovic N. Deep learning segmentation of Primary Sjögren's syndrome affected salivary glands from ultrasonography images. Comput Biol Med. 2021 Feb;129:104154. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0871 HERITABILITY AND PHENOTYPIC VARIATION OF SARCOIDOSIS IN THE ICELANDIC POPULATION
Authors: K. Stefansson, B. Árnadóttir, J. G. Jónsson, S. Ó. Haraldsdóttir, Þ. Gíslason, G. Jónsson, I. Jonsdottir, B. Gudbjornsson
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Studies on the etiology of sarcoidosis have shown contradictory results. It is generally accepted that the immune system of a genetically susceptible individual gets triggered by an unknown antigen, leading to granuloma formation in various organs. <h3>Objectives:</h3> The present study maps the pattern of familial distribution of all known, biopsy-verified sarcoidosis diagnoses made in a nationwide Icelandic population from 1981 till the end of 2021. <h3>Methods:</h3> All cases were re-confirmed and categorized into one of the five phenotypic groups described by Schupp et al. (2018). Distant relationships were accurately traced for relatives of sarcoidosis patients and their mates using the Icelandic Genealogy Database. This allows the creating of matched control groups as needed to calculate Relative Risk (RR), the Kinship Coefficient (KC), and their statistical significance. <h3>Results:</h3> In the study period, there were 462 patients with biopsy-proven diagnoses of sarcoidosis. We identified 282 extended families and seven sibling pairs with sarcoidosis. Twenty families had five or more affected individuals. RR was 3.7 (95% CI: 1.54,8.55) in 1<sup>st</sup>-degree relatives (P=0.003), 1.65 (95% CI: 1.05,1.92) in 4<sup>th</sup>-degree relatives, (P=0.014) and 1.57 (95% CI: 1.08,1.70) in 5<sup>th</sup>-degree relatives (P=0.003). RRs among 1st-5<sup>th</sup>-degree relatives of the patients' mates were not significant. KC for sarcoidosis was low and significant only for the first two meiosis (KC=1.06, P&lt;0.008 and KC=1.01, P=0.011, respectively). The most common sarcoidosis phenotypes were pulmonary (47.6%), ocular-cardiac-cutaneous and central nervous system (OCCC) (21.6%), and musculoskeletal cutaneous (MSC) (20.9%) sarcoidosis. There was no clustering of a single phenotype in the extended sarcoidosis families. <h3>Conclusion:</h3> Heredity is not a strong risk factor in our study population. The risk is strongest for 1<sup>st</sup> generation relatives of patients, and single phenotypes do not cluster in distinct families. The study provides important clinical information for treating physicians and contributes to understanding the etiology of the disease. <h3>REFERENCES:</h3> [1] Schupp JC, Freitag-Wolf S, Müller-Quernheim J. Phenotypes of organ involvement in sarcoidosis. Eur Respir J. 2018 Jan 25;51(1):1700991. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0250 GENERATION AND VALIDATION OF A HUMAN IMMUNE scFv LIBRARY FROM SJÖGREN’S SYNDROME SALIVARY GLAND B-CELLS
Authors: E. Corsiero, M. Caliste, E. Pontarini, M. Dal Ferro, M. Figini, E. Luison, D. Currado, M. Perretti, A. Nissim, M. Bombardieri
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Sjögren's syndrome (SS) is the second most common rheumatic autoimmune disorder with a prevalence of 0.5-1% in the adult population. Dryness of salivary (SG) and lacrimal glands is one of the major problems affecting the quality of life of SS patients. To date, the treatments aim to alleviate symptoms without restoring a proper water flux. A hallmark of SS is also the development of ectopic lymphoid structures (ELS) in the SG. ELS support functional germinal centre (GC) responses supporting <i>in situ</i> B-cell activation and differentiation into autoantibodies producing plasma cells. Besides the commonly described autoantibodies (i.e. anti-ribonucleoproteins Ro/La, rheumatoid factor), anti-muscarinic M3 receptor and anti-aquaporin autoantibodies have been observed in SS patients. <h3>Objectives:</h3> Our aim was to generate and validate an immune phage display human scFv antibody library from ELS+ SG of SS patients to develop high affinity antibodies to clarify the mechanisms of glandular dysfunction for the development of new diagnostics and targeted therapies. <h3>Methods:</h3> The immune scFv phage display library was generated from ELS+ SG B-cells of SS patients (n=30). Library repertoire to assess clonal diversity before and after biopanning was assessed by High-Throughput-Next-Generation-Sequencing (NGS) analysis. Recombinant human Ro60/SSA antigen was used to perform three round of biopanning. Selected anti-Ro60 scFv were expressed in a soluble format, purified and assessed for their integrity by SDS-PAGE and finally expressed as fully human/mouse IgG. Specificity was assessed <i>in vitro</i> by ELISA and IF/IHC on SG stromal cells and SG tissue from SS patients. Binding was assessed by SPR using a Biacore T200. <h3>Results:</h3> Here, we describe an immune scFv human antibody library generated from ELS+ SG of SS patients with an estimated diversity of 2.4 x 10<sup>9</sup> confirmed also by NGS analysis. The antibody library was used to screen monoclonal antibodies against the ribonucleoprotein Ro60/SSA. A soluble monoclonal scFv antibody against Ro60 (scFv-G2) was isolated from the library and expressed as full IgG. We observed reactivity towards stromal cells derived from SS SG and SS SG tissue. This shows the value of the SS immune antibody library to generate antibodies against SS-disease tissue antigens. <h3>Conclusion:</h3> The generation of SS disease-tissue associated antibodies could pave the way for the generation of new diagnostics and therapeutics for clinical use in SS, thus developing effective and targeted therapies. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> This work was supported by a research grant from Barts Charity (Grant G-002155 to E Corsiero). <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0023-PARE GRIT YOUR TEETH AND ENDURE – OR COULD WE DO SOMETHING ELSE?
Authors: C. Ziegler
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Newer research shows a direct correlation between various RMDs and diseases in teeth and gums. This of course is bad in itself, but being a person with an RMD the problems add up because so many have severe difficulties in hands, arms and jaw. A sufficient mouth hygiene with regular and frequent toothbrushing and flossing can therefore be quite a challenge for people with an RMD. Furthermore seeing a Dentist is expensive, can be painful and people do not go as often as they should. <h3>Objectives:</h3> The Danish Rheumatism Association had two purposes of drawing attention to the problem of RMD and teeth. 1)Give people with RMDs more knowledge and strengthen their self-management in this field 2)Political campaigning for subsidy to dental treatment. <h3>Methods:</h3> To reach our two objectives we started by identifying the problem among people with RMDs, this was done through a survey to members of our online user panel and meetings with different interest groups e.g. Danish Patients, Danish Rheumatologists and Danish Dentist Association. The Danish Rheumatism Association had specific focus in this area and we established contacts on a political level to improve and increase the possibilities of subsidy to more people with RMDs. <h3>Results:</h3> Our Member's magazine made an issue on dental problems and RMDs, enlightening the theme from different sides. We produced new content on our website and social media where experts gave some good advice, e.g. about saliva and periodontitis. Researchers presented their newest research results in local member groups. The Danish Parliament is going to read a bill in this matter in spring 2024. Hopefully this will improve the situation for people with RMDs when it comes to dental visits. We hope to get a chance to present the latest update on the matter during the upcoming eular congress. <h3>Conclusion:</h3> Research gave knowledge about dental problems and RMDs. By tailoring information and political campaigning we offer better self-management and hopefully will hopefully achieve the subsidy to people with RMDs to dental treatment. We do hope that other PARE members could gain from our results in this field. <h3>REFERENCES:</h3> [1] www.gigtforeningen.dk [2] P. Holmstrup et al: Comorbidity of periodontal disease: two sides of the same coin? An introduction for the clinician (2017). [3] The interrelationship of periodontitis and rheumatoid arthritis, Bolstad et al. 2019. [4] The close association between dental and periodontal treatment and oral ulcer course in Behcet`s disease: a prospective clinical study (Karacayli et al. 2009). [5] Oral Health and its Aetiological Role in Behcet`s Disease (Muncu et al. 2021). <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>