tbuckley/cabot-search huggingface dataset:
POS0354 MOLECULAR GENETICS IN ADULT-ONSET STILL’S DISEASE: NEXT-GENERATION SEQUENCING IN 23 PATIENTS AND LITERATURE REVIEW
Authors: D. Prieto-Peña, E. Labrador-Sánchez, N. Palmou-Fontana, R. B. Melero-González, F. A. Anton Pages, C. Álvarez-Reguera, N. Paz-Gandiaga, R. Blanco
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Molecular genetic techniques are becoming increasingly essential tools for the diagnosis of monogenic systemic autoinflammatory diseases (SAIDs). However, their role in the diagnosis of AOSD remains limited. Previous studies assessing potential genetic variants in AOSD have only assessed single coding regions of a few genes using Sanger sequencing. However, NGS panels are becoming the genetic technique of choice because they allow rapid and simultaneous analysis of complete coding sequence of several SAID-related genes. <h3>Objectives:</h3> To assess the usefulness of NGS panels in AOSD patients to improve diagnosis and management of the disease. <h3>Methods:</h3> Observational, multicenter study of all patients with AOSD diagnosis in whom NGS panel was performed in Northern Spain. Clinical manifestations, laboratory parameters, complications and therapeutic response was recorded. <h3>Results:</h3> 23 patients (15 men, 8 women) with a mean ± SD age of 42.0±18.1 years, in whom NGS was performed, fulfilled Yamaguchi criteria for AOSD. Most common manifestations, apart from fever, were skin rash (73.9%), asthenia (95.7%) and articular manifestations (91.3%). All patients had elevated acute-phase reactants levels and hyperferritinemia. Almost all patients received oral glucocorticoids as initial therapy. Conventional disease modifying anti-rheumatic drugs (cDMARDs) were used in 17 (73.9%) patients and biologic therapy in 12 (52.2%) patients. Genetic variants were observed in 5 (21.7%) patients. None of them were classified as pathogenic. Variants of uncertain significance (VUS) were identified in: <i>NOD2</i> (c.2104C&gt;T and c.2251G&gt;A), <i>TNFRSF1A</i> (c.224C&gt;T), <i>TNFAIP3</i> (c.1939A&gt;C) and <i>SCN9A</i> (c.2617G&gt;A). Atypical manifestations and/or therapeutic refractoriness were observed in patients carrying genetic variants, except from the patient with the <i>TNFAIP3</i> VUS <b>(Table 1</b>). <b>Table 2</b> summarizes previous reported data of genetic studies in AOSD patients. The prevalence of VUS varies widely across populations. Our results are in line with those reported in Caucasian population ranging from 15% to 27.8%. However, Asian studies found a higher frequency of VUS in MEFV. It is worth mentioning that none of our patients carried VUS in MEFV. <h3>Conclusion:</h3> To the best of our knowledge our study is the first to assess the role of NGS panel in AOSD patients. NGS was useful to rule out the presence of pathogenic genetic variants related to other SAIDs and to detect VUS that may help to identify patients at risk for atypical and severe manifestations and poor response to conventional therapy. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0235 NEW ONSET OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS: CLINICAL COURSE AND OUTCOMES FROM A EUSTAR DATABASE ANALYSIS
Authors: C. Bruni, L. Petelytska, A. Velauthapillai, L. Tofani, P. Carreira, G. Cuomo, E. Hachulla, I. Castellví, R. Bečvář, A. Balbir-Gurman, P. Airò, I. Litinsky, L. A. Saketkoo, J. K. De Vries-Bouwstra, M. Vonk, A. M. Hoffmann-Vold, M. Matucci-Cerinic, O. Distler
Journal: Annals of the Rheumatic Diseases (2024)
AB1687-PARE QUALITY OF LIFE AND ANXIETY-DEPRESSIVE DISORDERS IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS
Authors: Z. Syrine, S. Bouden, R. Leila, A. Ben Tekaya, I. Mahmoud, R. Tekaya, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Axial spondyloarthritis (AxSpA) is a chronic inflammatory rheumatic disease that affects young adults and can cause significant pain and functional disability. It may be accompanied by fatigue, anxiety and even depression which can have a negative impact on quality of life (QoL). <h3>Objectives:</h3> The aim of the study was to assess the level of QoL and the association of anxiety, depression and clinical factors with the quality of life of patients with axSpA. <h3>Methods:</h3> We conducted a cross-sectional study, including patients diagnosed with AxSpA according to ASAS 2009 criteria, followed at a tunisian Rheumatology Department. For each patient, sociodemographic, disease, and treatment data were assessed. Each patient completed the Hospital Anxiety and Depression Scale (HAD) questionnaire to screen for anxiety and depression, and the ASQol: Ankylosing Spondylitis Quality of Life questionnaire to assess quality of life (QoL) (score ranging from 0 (good QoL) to 18 (poor QoL)). <h3>Results:</h3> Our study included 105 patients with AxSpA, 67.6% of whom were men, with a mean age of 41.9 ± 13.76 years and a mean disease duration of 11.81 years [1-50]. Mean BASDAI was 4.46 ± 2.5 and mean BASFI was 4.87 ± 2.18. Mean CRP was 24.12 ± 10.2 mg/l. 62.3% of patients had coxitis, 9.1% of whom had undergone total hip replacement. Regarding the treatment, 10.47% were on biotherapy. Depression was noted in 49.5% of patients, with a mean HADS depression of 10.41 ± 3.6. Anxiety was noted in 64.7% of patients, with a mean HADS anxiety of 9.82 ± 4.3. For the quality-of-life score, the mean ASQoL was 8.27± 4.71. A high ASQoL, indicating impaired quality of life, was significantly associated with an early age of onset (p=0.04) and high CRP levels (p=0.01). A significant relationship was also found between HAD and hip involvement (p=0.001) and HAD correlated positively with BASDAI (p=0.002). <h3>Conclusion:</h3> These findings should encourage practitioners to screen AxSpA patients for anxiety and depressive disorders. Controlling factors associated to these indices, including inflammation, high disease activity and the presence of hip involvement is crucial to promote QoL. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0346 POTENTIAL THERAPEUTIC STRATEGIES FOR VEXAS SYNDROME BY TARGETING CELL DEATH
Authors: Y. Kirino, S. Adachi, A. Maeda, K. Takase-Minegishi, R. Yoshimi, H. Nakajima
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> VEXAS syndrome, a severe autoinflammatory disease resulting from an acquired somatic mutation in the UBA1 gene, currently lacks a definitive cure, posing a significant challenge for patients. <h3>Objectives:</h3> To unravel the mechanisms underlying cell death in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome using peripheral blood samples and to assess the clinical value of this knowledge. <h3>Methods:</h3> Nine patients undergoing treatment for VEXAS syndrome at Yokohama City University Hospital were included in this study. Monocytes and neutrophils were isolated from peripheral blood, and then monocytes were differentiated into polarized macrophages. Viable cell counts, cell death assays and measurements of various indicators such as HMGB1 concentration, extracellular ATP concentration, annexin V level, and caspase 1, 3 and 7 activities were performed. <h3>Results:</h3> Elevated cell death of monocytes and neutrophils was observed in VEXAS syndrome patients, as indicated by cultured cell counts and cell death assays. Annexin V assays and measurements of caspase 1, 3 and 7 activities suggested increased apoptosis and pyroptosis in these cells. Serum HMGB1 levels were significantly elevated in VEXAS syndrome patients and decreased after prednisolone (PSL) dose escalation. Monocytes and neutrophils from the VEXAS group exhibited heightened extracellular ATP secretion, which was significantly reduced by soluble PSL co-culture. Amount of extracellular ATP secretion of monocytes from VEXAS syndrome patients after co-culture with water-soluble prednisolone (ng/ml) assessed by RealTime-Glo Extracellular ATP Assay. Error bars indicate S.E. of the mean. *P &lt; 0.05, ****P &lt; 0.0001 by unpaired t-test or one-way ANOVA or ANCOVA. RLU:relative luminesence unit. <h3>Conclusion:</h3> This study confirms increased cell death of monocytes and neutrophils and damage-associated molecular patterns in VEXAS syndrome, and these findings may be valuable for drug screening, therapeutic strategies and as biomarkers. <h3>REFERENCES:</h3> [1] Maeda A, Tsuchida N, Uchiyama Y, Horita N, Kobayashi S, Kishimoto M, et al. Efficient detection of somatic UBA1 variants and clinical scoring system predicting patients with variants in VEXAS syndrome. Rheumatology (Oxford). 2023. [2] Tsuchida N, Kunishita Y, Uchiyama Y, Kirino Y, Enaka M, Yamaguchi Y, et al. Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis. Ann Rheum Dis. 2021;80(8):1057-61. [3] Beck DB, Ferrada MA, Sikora KA, Ombrello AK, Collins JC, Pei W, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. The New England journal of medicine. 2020;383(27):2628-38. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1396 ONTOLOGICAL ANALYSIS OF CO-EXPRESSED GENES IN THE PATHOGENESIS OF RENAL FIBROSIS IN THE CONTEXT OF LUPUS NEPHRITIS
Authors: R. Martinez-Canales, M. Montelongo Rojas, S. E. Rojas Gutierrez, C. Elizondo Solis, N. Macias-Segura, M. Salinas Carmona
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Lupus nephritis (LN) is a common complication of Systemic Lupus Erythematosus often carrying high mortality and morbidity. Fibrosis in LN has been detected in approximately 40% of adults with SLE [1], often accompanied by tubular atrophy. Even though glomerular injury has been the focus in the pathogenesis of LN, interstitial fibrosis is thought to be more indicative of severity injury and progression to renal failure [2], warranting further research on targets and mechanisms of interstitial fibrosis in LN. In this study, we analyzed co-expressed pathways in the pathogenesis of renal fibrosis in the context of LN using bioinformatics software. <h3>Objectives:</h3> We aimed to identify co-expressed genes starting from overrepresented genes in the human phenotype of renal fibrosis in samples of kidney biopsies. <h3>Methods:</h3> We downloaded the dataset GSE112943 from the GEO platform. This dataset contains 14 samples of kidney biopsies from patients with LN and 6 samples of healthy controls. We utilized the Gene Set Enrichment Analysis (GSEA) tool to identify overrepresented genes in the phenotype of renal fibrosis, which was downloaded from the Human Collection of the Molecular Signatures Database. To identify co-expressed genes, we input the overrepresented genes in the Genemania platform. We performed an ontological analysis on the co-expressed genes with the Database for Annotation, Visualization and Integrated Discovery (DAVID). We assessed protein-protein interactions (PPIs) using the StringApp via Cytoscape. <h3>Results:</h3> 6 genes were enriched in the cohort of patients with LN, while 20 genes were found to be co-expressed. Ontological analysis found that these genes participate in pathways related to apoptosis (Table 1). PPIs are shown in Figure 1. <h3>Conclusion:</h3> In this study, our results indicate that pathways of apoptosis in kidney tissues occurs along renal fibrosis in patients with LN. However, interactions among this set of genes seem to be scarce, as only 6 genes were found to interact between them. These findings warrant further research to understand the role of apoptosis in renal fibrosis secondary to LN. <h3>REFERENCES:</h3> [1] Maria, Naomi I, and Anne Davidson. "Protecting the kidney in systemic lupus erythematosus: from diagnosis to therapy." Nature reviews. Rheumatology vol. 16,5 (2020): 255-267. doi:10.1038/s41584-020-0401-9 [2] Hsieh, Christine et al. "Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring." Arthritis care &amp; research vol. 63,6 (2011): 865-74. doi:10.1002/acr.20441 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
OP0121 IMMUNE CELL SIGNATURES OF PATIENTS WITH DIFFERENT SUBTYPES OF BEHCET’S DISEASE
Authors: Q. Fu, H. Yuan, A. Xu
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Behcet's disease (BD) is a multisystem autoinflammatory disorder characterized by recurrent oral and genital ulcerations, skin lesions, uveitis, as well as vascular, neurological, and gastrointestinal manifestations[2]. Due to the heterogeneity of clinical manifestations, treatments appear to be differentially effective in patients with different systems involved[1]. The pathogenesis of BD is poorly understood and some of the critical questions remain unresolved in BD management including duration and choice of treatments for different subtypes of BD patients and "treat-to-target" strategies, etc. <h3>Objectives:</h3> This study aimed to identify immunological signatures among different subtypes of BD patients and look for theoretical basis for further precise targeted therapy. <h3>Methods:</h3> The landscape of 20 immune-cell phenotypes in the peripheral blood were measured by multi-color flow cytometry from 58 BD patients including 25 mucocutaneous type, 6 uveitis, 4 with central nervous system affected, 7 with vascular manifestation, 16 with gastrointestinal ulceration as well as 9 healthy donors. Statistical differences in quantitative parameters among two groups were determined using unpaired <i>t</i> test. Differences were considered statistically significant at P&lt;0.05. <h3>Results:</h3> The population of CD3<sup>+</sup>CD8<sup>+</sup> T cells in the blood of patients with mucocutaneous type, uveitis and gastrointestinal type were remarkably increased and higher than normal controls (P&lt;0.05). In addition, the peripheral proportion of CD3<sup>-</sup>CD56<sup>+</sup> NK cells in BD patients with uveitis was higher than that of normal controls, and was also significantly higher than that of mucocutaneous BD patients (P&lt;0.05). Compared with other subtypes of BD patients, the proportion of CD4<sup>+</sup>IL-17A<sup>+</sup> and CD4<sup>+</sup>RORγt<sup>+</sup> T cells in the peripheral blood of patients with vascular manifestation were not only higher than that of normal controls, but also remarkably increased in patients with mucocutaneous type (Figure 1). <h3>Conclusion:</h3> Peripheral immunological features may have the potential to stratify BD patients with different organ involved, which may have implications for precise target therapy selection. <h3>REFERENCES:</h3> [1] Liu, H., Zhang, P., Li, F., Xiao, X., Zhang, Y., Li, N., Du, L. &amp; Yang, P. (2023) Identification of the immune-related biomarkers in Behcet's disease by plasma proteomic analysis. <i>Arthritis Res Ther</i>, <b>25</b>, 92. [2] van der Houwen, T.B., van Hagen, P.M. &amp; van Laar, J.A.M. (2022) Immunopathogenesis of Behcet's disease and treatment modalities. <i>Semin Arthritis Rheum</i>, <b>52</b>, 151956. <h3>Acknowledgements:</h3> Professor Chen Dong, Westlake University School of Medicine. <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0740 URINARY NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) AS A MEDIATOR OF THE ASSOCIATION BETWEEN PARTICULATE MATTER EXPOSURE AND DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: S. S. Lee, J. H. Kang, S. E. Choi, D. J. Park, H. J. Baek, H. J. Choi, J. H. Jung
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> <h3>Objectives:</h3> Neutrophil gelatinase-associated lipocalin (NGAL) is an acute-phase glycoprotein increased by inflammatory stimuli, oxidative stress, and tissue injury. Although NGAL is associated with global and renal disease activity in systemic lupus erythematosus (SLE), it is not known whether particulate matter (PM) affects NGAL levels and lupus activity in these patients. Thus, we investigated the mediating role of NGAL in the association between PM<sub>10</sub> and PM<sub>2.5</sub> exposure and lupus activity in a prospective, longitudinal cohort. <h3>Methods:</h3> The study enrolled 386 patients from three metropolitan regions in Korea. The daily average PM<sub>10</sub> and PM<sub>2.5</sub> concentrations were measured using portable air quality monitors and based on data from the National Ambient Air Monitoring System. Urinary NGAL (uNGAL) was measured at the time of enrollment and at 12 months, and disease activity was evaluated using the SLE Disease Activity Index 2000 (SLEDAI-2K) every 3 months for 1 year. Mixed Cox proportional hazard regression was performed to evaluate the associations of PM<sub>10</sub> and PM<sub>2.5</sub> with uNGAL and SLE disease activity. <h3>Results:</h3> Changes in PM<sub>10</sub> and PM<sub>2.5</sub> were associated with changes in uNGAL (β = 1.038, 95% confidence interval [CI]: 1.017–1.059, <i>p</i> &lt; 0.001; β = 1.030, 95% CI: 1.001–1.045, <i>p</i> = 0.013, respectively), and with changes of SLEDAI-2K scores of &gt; 8 over 1 year in SLE patients (β = 0.097, 95% CI: 0.048–0.146, <i>p</i> &lt; 0.001; β = 0.100, 95% CI: 0.054–0.146, <i>p</i> &lt; 0.001, respectively). In addition, changes in uNGAL were significantly associated with changes in SLEDAI-2K scores of &gt; 8 (β = 1.000, 95% CI: 1.000–1.002, <i>p</i> = 0.043). <h3>Conclusion:</h3> The association between PM exposure and SLE disease activity may be partially explained by uNGAL levels. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
OP0115 IDENTIFICATION AND VALIDATION OF ANTI-PROTEIN ARGININE METHYLTRANSFERASE 5 (PRMT5) ANTIBODY AS A NOVEL PROPELLING ANTIBODY FOR SYSTEMIC SCLEROSIS (SSc)
Authors: M. Liang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> In the complex panorama of autoimmune diseases, characterization of pivotal pathogenic autoantibodies involved in disease progression remains challenging. <h3>Objectives:</h3> This study aimed to identify novel antibodies through a global antibody profiling strategy and elucidate the pathological implications and clinical significance of identified autoantibodies in systemic sclerosis (SSc). <h3>Methods:</h3> We implemented this strategy by conducting immunoprecipitation on the whole IgG/IgA binding proteins from SSc and healthy sera, utilizing antigen pools derived from extracts of cells, including human umbilical vein endothelial cells (HUVECs), human dermal fibroblasts (HDFs), Jurkat T cells and THP-1 monocytes. IgG/IgA binding proteins were proceeded with quantitative proteomics and over-presented by bioinformatics analysis. The identified antibodies were then orthogonally validated in a SSc cohort. Mice were immunized with the target antigen, and subsequent evaluation was conducted through histological examination and RNA-sequencing. <h3>Results:</h3> We detected 238 significantly upregulated IgG/IgA binding proteins. Amongst those, the concentrations of anti-PRMT5 antibodies were significantly elevated in SSc patients, demonstrating robust diagnostic accuracy in distinguishing SSc patients from healthy controls and other autoimmune diseases including Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SjS) with an area under the curve (AUC) of 0.900 to 0.988. Notably, 31.11% of SSc patients tested positive for anti-PRMT5 antibodies, and the correlation of their levels with the trajectory of disease progression or regression was assessed in the context of both skin and lung fibrosis. The pathogenetic effects of these antibodies were proven by immunization experiments. Mice immunized with PRMT5 displayed significant inflammation and fibrosis in both skin and lungs, accompanied by the enrichment of multiple proinflammatory and profibrotic pathways on RNA-seq. <h3>Conclusion:</h3> This study has identified anti-PRMT5 antibodies as a novel autoantibody in SSc and demonstrated their role as drives of inflammation and fibrotic tissue remodeling. <h3>REFERENCES:</h3> [1] Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med 2009;360(19):1989-2003. doi: 10.1056/NEJMra0806188. [2] Denton CP, Khanna D. Systemic sclerosis. Lancet 2017;390(10103):1685-99. doi: 10.1016/s0140-6736(17)30933-9 [published Online First: 20170413]. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1695-PARE FACTORS ASSOCIATED WITH NON-VACCINATION FOR INFLUENZA AND PNEUMOCOCCUS AMONG PATIENTS WITH CHRONIC INFLAMMATORY RHEUMATIC DISEASE (CIRD)
Authors: S. Ez-Zaoui, H. Rkain, N. Benzine, F. Kronbi, I. Bensaghir, S. Farih, R. Honsali, H. L ’heri, T. Latifa, N. Hajjaj-Hassouni, F. Allali
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Objectives:</h3> To evaluate the vaccination coverage of patients followed for CIRD against influenza, pneumococcus and to determine reasons related to non vaccination according to patients' point of view. <h3>Methods:</h3> This is a cross-sectional study, including patients followed for chronic inflammatory rheumatic disease (CIRD) in Morocco. Information about vaccination coverage and reasons for non-vaccination against influenza and pneumococcal infection were collected. <h3>Results:</h3> This survey included 230 patients (mean age of 46.9±13.89 years,68.7% females) affected by a CIRD (Rheumatoid Arthritis 53%, Spondyloarthritis 39.6%, Psoriatic arthritis 7%). This study showed a significant lack of influenza and pneumococcal vaccination in CIRD patients with a vaccination coverage against influenza and pneumococcal infection of 2.2%, 0.4% respectively. The main reason for non-vaccination against influenza and pneumococcus was related to doctors non recommendation to do so (77%, 87% p=0.04).Table 1 illustrates different reasons that prevent CIRD patients from getting vaccinated against influenza, pneumococcus <h3>Conclusion:</h3> This survey showed a lack of influenza and pneumococcal vaccination among CIRD patients. The principal actions to improve vaccination against influenza, pneumococcus should aim to educate both patients and rheumatologists. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0937 RESPONSE TO ALLOPURINOL AND FEBUXOSTAT ACCORDING TO THE FRACTIONAL EXCRETION OF URIC ACID
Authors: P. Richette, M. Resche-Rigon, Q. D. Nguyen, D. M. Do, T. Phuong Mai, T. D. Nguyen, E. Letavernier, T. Pascart, A. Latourte, Q. Huy, D. Huynh, H. K. Ea, T. Bardin
Journal: Annals of the Rheumatic Diseases (2024)