tbuckley/cabot-search huggingface dataset:
AB0851 CLINICAL AND RESPIRATORY FEATURES OF PRIMARY SJÖGREN’S DISEASE PATIENTS WITH INTERSTITIAL LUNG DISEASE
Authors: P. Panagopoulos, L. Chatzis, E. Chatzinikita, V. Pezoulas, K. Malagari, D. I. Fotiadis, T. Vassilakopoulos, A. Tzioufas, A. V. Goules
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Interstitial lung disease (ILD) is a relatively common pulmonary manifestation of primary Sjögren's Disease (pSjD)<sup>1</sup>, with significant impact on morbidity and quality of life among patients. <h3>Objectives:</h3> To describe the clinical and respiratory features of pSjD patients with ILD. <h3>Methods:</h3> Consecutive pSjD patients from the outpatient rheumatology clinic of the Department of Pathophysiology reporting exertional dyspnea, persistent dry cough for &gt; 3 months or abnormal pulmonary function tests (PFTs) as screening test, underwent high resolution computed tomography (HRCT) of the chest. HRCT scans were evaluated blindly by a specialized radiologist for the presence of ILD and small airways disease (SAD). Cumulative clinical, laboratory and immunologic data were also recorded. Pulmonary and small airways function were assessed by classic spirometry, measurement of diffusing capacity for carbon monoxide (DLCO), single breath nitrogen washout (N<sub>2</sub>SBW) and impulse oscillometry (IOS). <h3>Results:</h3> 84 consecutive pSjD patients with respiratory symptoms or abnormal PFTs were included in the study prospectively, between October 2022 and November 2023, and underwent HRCT scan. The mean±SD age of the 84 patients at pSjD onset was 50.5±13.7 years, the median disease duration from SjD onset until current evaluation was 9.5 years (range: 0-38) and the majority were females (93%). Thirty one (36.9%) patients had ILD findings on HRCT. pSjD-ILD patients presented more frequently with dyspnea and cough as assessed by the respiratory questionnaires [FACIT-D (median: 37.4 vs. 32.8, p=0.045), SGRQ (median: 20.4 vs. 9.8, p=0.045) and CAT (median: 3.5 vs. 1, p=0.015)] compared to non ILD-SjD patients. They also had worse small airways function indices [lower FEF<sub>25-75</sub> (mean: 73.9% vs. 93.8%, p=0.027), more frequently abnormal R5-R20 &gt; 0.07 kPa/L/s (61% vs. 34%, p=0.039)] and more commonly SAD findings on HRCT than non-ILD controls (26% vs. 8%, p=0.028) (Table 1). pSS-ILD patients had more often positive ANA (90% vs. 79%, p=0.044), higher focus score on labial minor salivary gland biopsy at SjD diagnosis (3.11 vs. 1.88, p=0.017) and history of lymphoma (32% vs. 11%, p=0.039). <h3>Conclusion:</h3> Interstitial lung disease is very common in pSjD and is characterized by apparent respiratory manifestations, higher focus score at diagnosis and strong association with small airways disease. <h3>REFERENCES:</h3> [1] Kampolis et al. Clin Exp Rheumatol. 2018;36 Suppl 112(3):94-101. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1400 DETERMINANTS OF IDIOPATHIC ORIGIN IN UVEITIS
Authors: O. Dhrif, H. Bettaieb, W. Khemiri, B. Manel, R. Bourguiba, W. Helali, A. Zahaf, H. Lajmi, B. Ben Achour, M. H. Douggui, S. Bellakhal
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The diagnosis of uveitis is often straightforward and relies on the ophthalmologic examination. The challenge lies in determining the origin, a crucial step for establishing appropriate management procedures [1]. <h3>Objectives:</h3> The aim of the study is to investigate factors associated with idiopathic origin in uveitis. <h3>Methods:</h3> We conducted a cross sectional study in patients with uveitis. The diagnosis of uveitis was established after ophthalmic examination. Patients were then grouped into an idiopathic uveitis group (IUG) and a secondary uveitis group (SUG). Categorical variables were compared with the χ2 –test or Fisher's test. Comparisons of the differences of continuous variables were performed by the Mann–Whitney U test or Student's t-test. <h3>Results:</h3> Overall, 55 patients (22 in IUG and 33 in SUG) were enrolled. The mean age was 42 ± 14 and 40 ± 10 years old in IUG and SUG (p=0.458) respectively. The sex ratio (F/M) was 1.4 and 0.6 in IUG and SUG (p=0.109) respectively. Etiologies in the SUG were as follows: Behçet disease (n=17), spondyloarthritis (n=4), sarcoidosis (n=3), Vogt Koyanagi Harada disease (n=2), local ophthalmological condition (n=2), Toxoplasmosis (n=2), Herpes virus (n=1), hemorrhagic rectocolitis (n=1) and systemic lupus erythematosus (n=1). Extraocular involvement was noted in one patient in IUG (4.5%) and 27 patients in SUG (82%) (p&lt;0.001). Uveitis was bilateral in 36% of cases in IUG (vs 58% of cases in SUG; p=0.123) and recurrent in 56% of cases in IUG (vs 42% of cases in SUG; p=0.378). Characteristics of uveitis in IUG and SUG are presented respectively. anterior uveitis (73% vs 36%; p=0.008), vitreitis (32% vs 46%; p=0.312), panuveitis (18% vs 36%; p=0.146), granulomatous character (32% vs 15%; p=0.188), presence of synechiae (55% vs 42%; p=0.378), presence of retinal vasculitis (18% vs 42%; p=0.061), serous retinal detachment (0 vs 15%; p=0.056), hypertonic uveitis (32% vs 9%; p=0.032) and presence of macular oedema (5% vs 18%; p=0.223). <h3>Conclusion:</h3> All uveitis cases should undergo an etiological investigation. The diagnostic approach must be tailored based on clinical data. The etiological assessment should be comprehensive. As demonstrated by our study, the presence of extraocular manifestations, posterior involvement and elevated ocular tension may guide towards a secondary origin encouraging exhaustive etiological assessment. <h3>REFERENCES:</h3> <i>[1] Choi RY et al. Reclassifying Idiopathic Uveitis: Lessons From a Tertiary Uveitis Center. Am J Ophthalmol. 2019;198:193-199.</i> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1426 RAB19 AND PANCREATIC INJURY IN PATIENTS TAKING AZATHIOPRINE: A GENOME-WIDE ASSOCIATION STUDY
Authors: S. Shah, T. Reese, L. Daniel, P. Nepal, J. Zanussi, A. Dickson, R. Tao, A. Hung, W. Q. Wei, C. M. Stein, Q. Feng, C. Chung
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Pancreatitis is a rare, but potentially life-threatening adverse event associated with the use of azathioprine. Prior studies have found an association between the HLA region and thiopurine-induced acute pancreatitis (TIAP); however, TIAP is generally a diagnosis of exclusion—made only after all other possible causes of pancreatitis have been eliminated. More recently, drug-associated pancreatic injury has been viewed as a continuum that occurs concurrent with other risk factors for pancreatic injury. <h3>Objectives:</h3> We aimed to identify novel genetic risk factors associated with pancreatic injury in patients taking azathioprine using genome-wide association studies (GWAS). <h3>Methods:</h3> This was a retrospective study of patients with inflammatory conditions taking azathioprine. We used electronic health records linked to genomic data from two independent cohorts of White patients—BioVU (Vanderbilt's biobank) for discovery and NIH's <i>All of Us</i> for replication. We excluded patients who underwent organ transplant. The primary outcome was pancreatic injury defined by amylase or lipase levels greater than twice the upper limit of normal while taking azathioprine. In total, we analyzed ~7.1 million single-nucleotide polymorphisms. We conducted the analyses using Firth logistic regression adjusting for 10 principal components, sex, age, and two azathioprine indication variables (inflammatory bowel disease and all others). <i>All of Us</i> does not permit reporting of exact numbers &lt;20. <h3>Results:</h3> Forty-two patients with pancreatic injury and 2085 control subjects were included from BioVU; the <i>All of Us</i> cohort included &lt;20 patients with pancreatic injury and 847 control subjects. The GWAS analysis in the BioVU cohort identified an association between pancreatic injury and a SNP at the <i>RAB19</i> locus (rs2948386, OR=3.47, p=1.46 x 10<sup>-8</sup>); the association was replicated in the <i>All of Us</i> cohort (OR=2.70, p=4.18 x 10<sup>-3</sup>). <h3>Conclusion:</h3> In summary, we identified rs2948386 at the <i>RAB19</i> locus as a novel genetic factor for azathioprine-associated pancreatic injury. Previous reports indicate that <i>Rab19</i> plays a role in autophagy and the severity of pancreatitis in animal models support its potential underlying mechanistic involvement. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> We gratefully acknowledge All of Us participants for their contributions, without whom this research would not have been possible. We also thank the National Institutes of Health's All of Us Research Program for making available the participant dataexamined in this study. <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0123 IMMUNE-RELATED ADVERSE EVENTS IN PATIENTS WITH A PRE-EXISTING AUTOIMMUNE OR INFLAMMATORY DISEASE TREATED WITH IMMUNE CHECKPOINT INHIBITORS: A NATIONWIDE DATABASE COHORT STUDY
Authors: X. Jannot, N. Sedmak, E. Sauleau, J. Sibilia, J. E. Gottenberg, E. Sebbag
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> In about 10% of patients, the immune response to immune check-point inhibitors (ICI) exceeds the anti-tumor response and leads to autoimmune complications (immune-related Adverse Events, irAEs), which can sometimes be severe and require the use of targeted therapies. Pre-existing autoimmune disease (AD) seems to increase the risk of irAE in patients treated with ICI. <h3>Objectives:</h3> To compare the prevalence and mortality of irAEs in patients with or without a pre-existing autoimmune or inflammatory disease. <h3>Methods:</h3> This retrospective study analyzed adults from the French nationwide healthcare information system ("système national des données de santé" [SNDS]) who initiated any immune checkpoint inhibitor (ICI) therapy for any cancer between 2016 and 2022. The aim was to investigate the occurrence of immune-related adverse events (irAEs) during ICI treatment and in the 12 months post-administration, comparing patients with and without a history of autoimmune disease. IrAEs were defined by the combination of (1) hospitalization for a cause evoking an irAE of any nature, and (2) either the initiation of corticosteroids, or of a conventional DMARD or a b/tsDMARD, or death. Propensity score matching was performed for patients with and without a pre-existing autoimmune or inflammatory disease. The propensity score included gender, age, type of cancer, type of ICI, time from cancer to initiation of ICI and from initiation of ICI to irAE, use of corticosteroids, hospitalization in intensive care unit, type of irAE, number of LTDs, Charlson's index and FDep social deprivation index. Overall survival was compared between the two groups using a Cox model. <h3>Results:</h3> 69,745 patients (men: 69.0%, mean age: 65.8 years) initiating an ICI were analysed. 5,252 (7.4%) patients had a pre-existing autoimmune or inflammatory disease, before initiation of ICI, notably including 594 patients with rheumatoid arthritis and 847 patients with inflammatory bowel disease. IrAE occurred in 568 patients (11%) in patients with a pre-existing autoimmune or inflammatory disease and 4374 patients (6.8%) without a pre-existing autoimmune or inflammatory disease, with a statistically significant increased risk (HR 3.07 (2.78-3.39)). Mortality was significantly increased in patients with a pre-existing autoimmune or inflammatory disease (HR 1.16 (1.1-1.22)). <h3>Conclusion:</h3> This extensive epidemiological nationwide study identified an increased risk of irAEs and a higher mortality in patients with a pre-existing autoimmune or inflammatory disease. Further investigations are needed to confirm and elucidate the determinants of these findings. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1128 SINGLE-CELL RNA SEQUENCING REVEALS CROSS-DISEASE CHARACTERIZATIONS OF TREATMENT-NAÏVE AUTOIMMUNE DISEASES AND DISTINCT INTERFERON SIGNATURES IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Z. Zhang, Y. Fan, Y. Geng, X. Ye, J. Zhao, H. Huang, J. Zhang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Autoimmune diseases encompass a wide array of conditions characterized primarily by immune dysregulation, comprising hundreds of distinct diseases. However, the pathogenic mechanisms of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and inflammatory arthritis diseases like rheumatoid arthritis (RA) and spondyloarthritis may exhibit substantial differences <sup>[1]</sup>. <h3>Objectives:</h3> To offer additional insights and clues into the pathogenesis of autoimmune diseases by using single-cell sequencing technology. <h3>Methods:</h3> Peripheral blood mononuclear cells (PBMC) from 14 treatment-naïve patients with autoimmune diseases, including 6 cases of RA, 4 cases of psoriatic arthritis (PsA), and 4 cases of SLE, along with 5 healthy control subjects were prospectively collected. Single-cell RNA sequencing (scRNA-seq) were performed using the 10x Genomics Single Cell technique. <h3>Results:</h3> From a total of ~130,000 cells, we identified 10 major clusters comprising 30 subtypes of cells. Comparing with the healthy control group, CD4+ effector memory cells showed a significant increase in RA and PsA patients, but no significant change in SLE. Conversely, CD14+CD16+ monocytes only showed a significant increase in SLE. Unswitched memory B cells and γδT cells in patients with autoimmune diseases exhibited a decrease in proportion, with the most pronounced decrease in SLE, followed by RA. Notably, GSEA analysis demonstrated a significant enhancement in the inflammatory response gene scores in all three patient groups, with the most significant increase in SLE. Furthermore, the type I interferon response genes and, especially Interferon Alpha And Beta Receptor Subunit 1/2 (IFNAR1/2) were significantly increased only in SLE, primarily expressed in the monocyte, DC, NK, and plasma cell subgroups. Meanwhile, type II interferon response genes showed a significant increase in SLE, a mild increase in RA, and no increase in PsA. Transcription factor analysis revealed the critical role of IRF7-STAT1 in regulating the type I interferon response in SLE. <h3>Conclusion:</h3> Different autoimmune diseases may present distinct immune cell landscape at single cell levels. SLE exhibits a more unique interferon signatures, regulated by IRF7-STAT1. The notable elevation of IFNAR1/2 exclusively in SLE patients implies that the potential efficacy of type I interferon receptor antagonists may be limited in SLE, but possibly not in inflammatory arthritis. <h3>REFERENCES:</h3> [1] Zeng L, Yang K, Zhang T, et al. Research progress of single-cell transcriptome sequencing in autoimmune diseases and autoinflammatory disease: A review. J Autoimmun. 2022;133:102919. doi:10.1016/j.jaut.2022.102919 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1419 CLINICAL ANALYSIS OF FOUR CASES OF PACHYDERMOPERIOSTOSIS
Authors: Z. Q. Tao, Q. H. Li, L. Dai
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Pachydermoperiostosis is a rare genetic disorder primarily impacting the skin and skeletal system. This condition is characterized by a range of symptoms including thickening of the skin (pachydermia) and abnormalities in bone growth and formation (periostosis). The exact etiology of Pachydermoperiostosis remains unclear; however, it is thought to be influenced by genetic legacy transmission. <h3>Objectives:</h3> Pachydermoperiostosis is a rare genetic disorder affecting the skin and skeletal system. This study aims to elucidate its clinical features through a case series, enhancing the understanding and diagnostic approach of the disease. <h3>Methods:</h3> We retrospectively analyzed clinical data from four patients diagnosed with pachydermoperiostosis at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from 2017 to 2023. This analysis included clinical presentations, laboratory findings, imaging results, and genetic testing. <h3>Results:</h3> The patients, all male, had a mean age of 22 years (range 21-23 years) and an average onset age of 15 years (range 9-18 years). Notable family history included one patient with an affected uncle and another with consanguineous but asymptomatic parents. Common symptoms were clubbed fingers/toes, skin thickening, and acne. Other findings included frontal wrinkles, nasolabial fold thickening (in three patients), hyperhidrosis (in two), and joint swelling/stiffness (in one). Three patients showed elevated carcinoembryonic antigen levels. Imaging revealed turbinate hypertrophy, meningeal thickening, scalp furrow changes, and periosteal thickening in the phalanges, tibia, fibula, ulna, and radius. One case presented with recurrent hypokalemia and was diagnosed with potassium-losing nephropathy. Genetic analysis identified a homozygous mutation in the SLCO2A1 gene (c.1406C&gt;T, p.Pro469Leu) in one patient, predicted as pathogenic by REVEL, SIFT, and Polyphen2 software. This mutation, previously reported in a compound heterozygous state, was found in asymptomatic parents, suggesting autosomal recessive inheritance. <h3>Conclusion:</h3> The study highlights that pachydermoperiostosis predominantly affects adolescent males and presents with diverse symptoms including skin and skeletal changes, elevated carcinoembryonic antigen, and in some cases, potassium-losing nephropathy. The identification of the SLCO2A1 gene mutation (c.1406C&gt;T) as a potential autosomal recessive pathogenic variant underscores the genetic underpinnings of this rare condition. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1135 FLUCTUATING CHANGES IN T CELLS DURING PREGNANCY IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: V. Röhm, J. Henes, R. Klein, A. C. Pecher
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) poses unique challenges during pregnancy due to high prevalence of complications; yet the interaction between immunological adaptations in pregnancy and SLE pathophysiology resulting in disease flares has not been elucidated. <h3>Objectives:</h3> This study aims to investigate T-helper (Th) subgroups in SLE patients throughout pregnancy and the postpartum period to evaluate their role during gestation. <h3>Methods:</h3> A monocentric prospective cohort study was conducted involving SLE patients in our clinic from January 2022 to April 2023. Peripheral blood samples of 7 SLE pregnancies were collected at every trimester and postpartum with flow cytometry analysis of Th-cells. Statistical analysis was performed using Mann-Whitney test. <h3>Results:</h3> We observed a significant increase in proinflammatory Th1-cells during the third trimester compared to the second semester and decline in the postpartum period. Th2-cells showed these fluctuations as well, but not significantly. T-regulatory cells (Treg) showed signs of decline from the first to the second trimester and a rise till the postpartum period. The proinflammatory Th17-cells stayed stable during pregnancy and decline postpartum. <h3>Conclusion:</h3> As SLE is considered a Th2-mediated disease and we notice a physiological rise of Th2-cell levels during pregnancy, this could possibly be associated with SLE flares during pregnancy. However, this cohort is yet too small to make conclusive statements regarding the correlation between immunologic changes and disease activity and therefore this analysis will be continued in the future. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Victor Röhm Eli Lilly, Jörg Henes ABVVIE, Astra-Zeneca, GSK, Janssen, Novartis, UCB, Reinhild Klein: None declared, Ann-Christin Pecher: None declared.
POS0276 ANTICOAGULANT TREATMENT IN ADDITION TO IMMUNOSUPPRESSIVES DECREASES THE RELAPSE RATE IN PULMONARY ARTERIAL INVOLVEMENT OF BEHÇET’S DISEASE
Authors: K. Abacar, A. E. Boncukcuoğlu, A. Aksoy, D. Kocakaya, Ç. Cimşit, H. Direskeneli, F. Alibaz- Oner
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Vascular inflammation in Behcet's Disease (BD) is one of the most important causes of mortality due to pulmonary artery involvement (PAI) or Budd-Chiari syndrome. <h3>Objectives:</h3> In this study, we aimed to retrospectively evaluate the clinical features, course and factors affecting the recurrence risk of BD-associated PAI. <h3>Methods:</h3> BD patients followed up between 1990-2022 were included. All data were acquired from the patient charts. Involvements were classified according to the vascular structures in which thrombotic or aneurysmal formation was detected. Factors affecting the risk of relapses were determined using multivariate Cox regression analysis. <h3>Results:</h3> Among 1350 BD patients, 110 (8.1%) had PAI. The mean age (SD) of patients with PAI was 42.4 (11.6) years, and the male/female ratio was 2.2 (76/34). Thirty-two (29.1%) of 110 patients were asymptomatic. Symptomatic patients were significantly older (p=0.031), and female gender (p=0.001) and recurrence (p=0.019) rates were higher than asymptomatic patients. Thrombotic involvement was seen in 104 (94.5%) and aneurysms in 9 (6.6%) patients. (Figure 1) Relapses were observed at least once in 31 (28.2%) patients. In multivariate analysis, the Cox regression model was significant (p=0.015) and not starting anticoagulants (HR 5.11, 95% CI 1.21-21.6), p=0.026), independently increased the relapse risk. (Table 1) <h3>Conclusion:</h3> PAT is the main presentation type of PAI in BD while aneurysmatic formation is rare. In one-third of patients with PAI, relapses develop during follow-up despite immunosuppressive treatment. When added to immunosuppressive treatment, anticoagulant therapy significantly decreases the relapse rate in BD patients with PAI. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>