tbuckley/cabot-search huggingface dataset:
AB0798 PRIMARY SJOGREN’S SYNDROME – IS IT WELL KNOWN IN GENERAL MEDICAL PRACTICE?
Authors: M. Panchovska, L. Despotova-Toleva, M. Proshenska, B. Boteva
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Primary Sjogren's syndrome belongs to the group of rare diseases. Secondary forms of the disease are diagnosed promptly by specialist rheumatologists, but primary forms of the syndrome remain unrecognized for a variously long periods of time. Patients are referred to different specialists. Rheumatologists diagnose primary Sjogren's syndrome at a relatively late stage (1,2). <h3>Objectives:</h3> This retrospective study assessed the level of awareness of general practitioners towards the diagnosis of primary Sjogren's syndrome by the number of patients referred to a specialist rheumatologist because of persistent "sicca'' symptoms. <h3>Methods:</h3> Retrospective study, based on electronic patients records <h3>Results:</h3> The diagnoses of 987 patients from the registry of rheumatologist from pre-hospital care for the period 2016 - 2019 were analyzed. Of these, 89 patients (9.01%) were referred for consultation by a general practitioner due to "sicca" symptoms. The average age of female patients was 55+- 13.5 years (N-78), and of male patients (N=11) is 47 +- 11.3 years. The frequency of symptoms is as follows: xerostomia - 49 patients out of 89 (55.05%), xerophthalmia (44 patients out of 89 - 49.43%), joint symptoms plus,,sicca ''symptoms (19 patients-21.34%), swelling of the parotid glands-7 patients (7.88%). The fact that for a period of 3.5 +- 2.3 years the patients were sent for consultations to specialists, other than a rheumatologist (ophthalmologists, dentists, endocrinologist, maxillofacial surgeons, infectionists etc), makes an impression. Out of a total of 987 patients consulted for the period 2016-2019, 89 of them have "sicca" symptoms. Criteria for primary Sjogren's syndrome covered 31 patients at the end of the rheumatological examinations and tests, which represents 3.14% for the studied retrospective 3-years period. <h3>Conclusion:</h3> Patients with "sicca" symptoms are initially referred by general practitioners to other specialists. The presence of joint symptoms shortens the patient's path to the specialist rheumatologist. Multidisciplinary training of family physicians is necessary for timely diagnosis of primary Sjogren's syndrome. <h3>REFERENCES:</h3> [1] Practical guidelines for the early diagnosis of Sjögren's syndrome in primary healthcare. [2] Sisó-Almirall A, Meijer JM, Brito-Zerón P, Conangla L, Flores-Chavez A, González de Paz L, Bootsma H, Ramos-Casals M. Clin Exp Rheumatol. 2021 Nov-Dec;39 Suppl 133(6):197-205. doi: 10.55563/clinexprheumatol/pal3z7. Epub 2021 Nov 29. [3] Prevalence of Sjögren's syndrome in patients with dry mouth in the region of Central Hungary. [4] Dézsi AJ, Erdei C, Demeter T, Kovács A, Nagy G, Mensch K, Németh O, Hermann P, Tóth G, Füst Á, Kiss EV, Kőhidai L, Zalatnai A, Márton K. Oral Dis. 2023 Oct;29(7):2756-2764. doi: 10.1111/odi.14264. Epub 2022 Jun 7. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1165 LAG-3 IS IMMUNE-PROTECTIVE IN SYSTEMIC SCLEROSIS
Authors: M. Aspari, S. R. Greisen, V. Ong, K. Soendergaard, E. Naeser, C. P. Denton, D. Abraham, B. Deleuran
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic Sclerosis (dcSSc) is an autoimmune disorder that affects the connective tissue. It is characterized by the thickening of the skin, which can lead to the fibrosis of internal organs. Although the overactivation of the immune system and increased proinflammatory cytokine production can explain the pathophysiology of this disease to a certain extent, the mechanisms leading to this are not well understood. Checkpoint inhibitory molecules function as physiological brakes in the immune system and help to maintain homeostasis. Aberrant checkpoint inhibitory pathways are often observed in patients with dcSSc. Lymphocyte activation gene-3 (LAG-3) is a late checkpoint inhibitory receptor that is mainly expressed by T cells and is involved in T cell inhibition. In this study, we focused on the role of LAG-3 in dcSSc and the effect of a LAG-3 agonist on immune cells from these patients. <h3>Objectives:</h3> This study aims to analyse the role of LAG-3 dcSSc and the influence of a LAG-3 Agonistic antibody in influencing inflammation and fibrosis. <h3>Methods:</h3> Plasma LAG-3 levels of 36 patients with dcSSc were compared to 20 healthy controls. PBMC's from eight dcSSc patients and four Healthy Controls were analysed by flow cytometry for the surface expression of LAG-3 on CD4+ and CD8+T cells after stimulation with CD3/CD28 for 24 hours. Eight dcSSc PBMC's were stimulated for 48 h with a LAG-3 Agonistic antibody and an isotype control. The harvested supernatants were analysed using a multiplex proinflammatory cytokine ELISA. <h3>Results:</h3> Patients with dcSSc had decreased soluble levels of LAG-3 compared with healthy controls (p &lt;0.0001). Increased surface expression of LAG-3 was observed in CD4+ T cells(p=&lt;0.05) and CD8+ T cells(p=&lt;0.005) in patients with dcSSc compared to healthy control PBMCs. When treated with a LAG-3 agonistic antibody (LAG-3 Ag), PBMC monocultures from dcSSc patients significantly downregulated the production of IFN gamma, IL-2, IL-4 and TNF alpha and upregulated the production of IL-10 as compared to non-treated controls(NT) (*=p&lt;0.05,**=p&lt;0.005). The Isotype control did not show a similar effect. <h3>Conclusion:</h3> LAG-3 is immune-protective in Systemic Sclerosis and its agonistic antibody could be used as a potential treatment modality. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1205 ACE GENE 1 POLYMORPHISM ASSOCIATION WITH RENAL FUNCTION IN SYSTEMIC SCLEROSIS
Authors: B. Karanović, M. Barešić, A. Merkler Šorgić, B. Anić
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Angiotensin-converting enzyme (ACE) 1 gene polymorphisms have been implicated in various diseases affecting the kidneys, with most studies implicating an association of the D allele or DD genotype with the susceptibility to a certain disease, such as end-stage renal disease (ESRD), diabetic nephropathy and IgA vasculitis nephritis. Other studies, however, do not show an association between ACE 1 gene polymorphisms and progression of renal failure in polycystic kidney disease or kidney function in renal transplant patients. The role of ACE 1 gene polymorphisms in systemic sclerosis-associated renal disease (SSc-RD) remains unknown. <h3>Objectives:</h3> The aim of the study was to determine whether ACE 1 gene polymorphisms have an effect on renal function in systemic sclerosis (SSc). <h3>Methods:</h3> We are presenting a retrospective observational study in patients with SSc and analysing the association of ACE 1 gene polymorphisms (DD, II and ID) with renal function measured by creatinine values, estimated glomerular filtration rate (eGFR) and proteinuria over three different periods of time (at the time of the diagnosis, 5 and 10 years after the diagnosis). At the time of diagnosis data was available for 135 patients, after 5 years of follow-up for 105 patients and after ten years of follow-up for 70 patients. In statistical analysis Kruskal-Wallis test was used with p value &lt;0.05 considered statistically significant. <h3>Results:</h3> We found no statistically significant differences in renal function in SSc patients according to their ACE gene 1 polymorphism over the analysed periods (at the time of diagnosis creatinine values p=0.823, eGFR p=0.327, proteinuria p=0.364, after 5 years creatinine values p=0.972, eGFR p=0.562, proteinuria p=0.764, after 10 years creatinine values p=0.469, eGFR p=0.181, proteinuria p=0.440). During 10 years of follow up, SSc renal crisis occurred in just one patient and there was no statistical difference observed in dynamics of creatinine values, eGFR and proteinuria during 10 years of follow-up between different groups of patients according to their polymorphism. <h3>Conclusion:</h3> Our study suggests that ACE 1 gene polymorphisms do not have a role in renal function in SSc. However, further studies are needed to explain the exact role of ACE 1 gene polymorphisms in SSc renal disease and SSc in general. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1166 EXTENDED RELEASE OF INHALED ILOPROST LIPOSOME (L608) FOR TREATMENT OF SYSTEMIC SCLEROSIS-RELATED RAYNAUD PHENOMENA AND DIGITAL ULCER
Authors: K. C. Chen, P. Kan, H. F. Liang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Iloprost has been approved in Europe for treatment of systemic sclerosis (SSc)-related Raynaud Phenomena (RP) and digital ulcer (DU) for decades. The current recommended treatment regimen with continuous intra-venous infusion for 6 hours a day during the consecutive 5 days is inconvenient and time-consuming. However, low oral availability and short half-life of iloprost restrict further clinical development. Inhalation of the extended release formulation of iloprost is therefore proposed in this study for the clinical application. <h3>Objectives:</h3> Inhalation of iloprost liposome (L608) was conducted in rat via intra-tracheal administration. The pharmacokinetic (PK) profile of iloprost in plasma was investigated and simulated to evaluate the potential of achieving the recommended plasma level via IV infusion. <h3>Methods:</h3> The liposomal iloprost solution (L608) was prepared and characterized in terms of assay and encapsulation efficiency. The test articles (L608 and iloprost solution) were administered by microsprayer for pharmacokinetic (PK) study in rats. Blood samples over 12 hours post-dosing were taken and analyzed by LC-MS-MS. The PK profile of L608 with the proposed dose regimen via oral inhalation route was then simulated to compare with the plasma level of IV infused iloprost solution for treatment of SSc-RP/DU. <h3>Results:</h3> The single doses of L608 via intra-tracheal (IT) administration are compared with those via IT and IV injection of iloprost solutions at the same dose (60 mcg/kg) in rats. L608 provides an extended iloprost plasma level as compared with iloprost solutions administration via IT and IV. Assuming that pulmonary adsorption rate and in-vivo metabolism of iloprost between rat and human are similar with the established dose proportionality [1], the human PK simulations indicate that two to three inhalation doses of L608 are able to achieve the extended plasma concentration as iloprost solution administered at IV infusion rate of 0.5 – 2.0 ng/kg/min, which is approved in Europe for treating SSc-RP/DU patients. <h3>Conclusion:</h3> Based on the rat PK data of sustained-release L608, the convenient dosage regimen with two to three inhalations per day is simulated to achieve the required plasma level for 6 hours a day, implying the potential to patient care. <h3>REFERENCES:</h3> [1] Eur Respir J (2022) 60:Suppl.66, 1622. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Ko-Chieh Chen Pharmosa Biopharm Inc., Pharmosa Biopharm Inc., Pei Kan Pharmosa Biopharm Inc., Pharmosa Biopharm Inc., Hsiang-Fa Liang Pharmosa Biopharm Inc., Pharmosa Biopharm Inc.
AB1168 POSTN AND IGF1 ARE POTENTIAL BIOMARKERS FOR INTERSTITIAL LUNG DISEASE IN DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS
Authors: J. He, Y. Zhou, C. Yi, J. Huang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic sclerosis (SSc) is an autoimmune disease with multiple complications. Interstitial lung diseases (ILDs) are significantly associated with SSc and are particularly related to diffuse cutaneous SSc (dcSSc). <h3>Objectives:</h3> This article aims to explore potential molecular mechanisms and develop new diagnostic biomarkers for dcSSc-ILD. <h3>Methods:</h3> The series matrix files of SSc and non-specific interstitial pneumonia (NSIP) were downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs). The co-expressed differential expressed genes (co-DEGs) between limited cutaneous SSc (lcSSc), dcSSc and NSIP groups were identified by Venn plots, and then selected for different enrichment analyses and protein–protein interaction (PPI) network construction. The mRNA expression levels of <i>POSTN</i> and <i>IGF1</i> were validated in online datasets. <h3>Results:</h3> DEG analysis revealed 66 shared genes in dcSSc and NSIP, while 5 shared genes in lcSSc and NSIP. The unique co-DEGs between dcSSc and NSIP were closely related to extracellular matrix organization, cell-substrate adhesion, leukocyte adhesion to vascular endothelial cell. We identified that <i>POSTN</i> and <i>IGF1</i> were important gene signatures in the dcSSc-ILD by PPI analysis. These two genes were showed a positive correlation with more immune cells abundance in dcSSc than lcSSc. And The expression levels of <i>POSTN</i> and <i>IGF1</i> were significantly increased in SSc-ILD patients. <h3>Conclusion:</h3> <i>POSTN</i> and <i>IGF1</i> contributed to the pathogenesis of dcSSc-ILD, which could be used as potential diagnostic and therapeutic targets. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1181 COMPARISON OF LL37 LEVELS BETWEEN SYSTEMIC SCLEROSIS AND RHEUMATOID ARTHRITIS PATIENTS- A PILOT STUDY
Authors: S. Giryes, N. Yeshurun Finkelstein, M. Kaplan, V. Shataylo, R. Erlich, A. Arraf, Y. Braun-Moscovici, A. Balbir-Gurman
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> LL37 is a human cathelicidin peptide reported to have antimicrobial and immunomodulatory activity. Excess levels of LL37 are thought to correlate with enhanced local inflammation in various diseases, including rheumatoid arthritis (RA), psoriasis and systemic lupus erythematosus[1, 2]. Lower levels of LL37 were found in patients with systemic sclerosis (SSc) and interstitial lung disease (ILD), but no differences were found between SSc patients without ILD and healthy controls[3]. <h3>Objectives:</h3> To compare LL37 blood levels in SSc and RA patients and their correlation with clinical features. <h3>Methods:</h3> Blood samples were taken from 18 SSc patients (13 diffuse SSc,5 limited SSc) with a mean age of 52 years (14 female), and from 13 RA patients with a mean age of 60 years (9 females) during routine rheumatology clinic visits or admission to rheumatology department. Levels of LL37 were measured using the ELISA method. Data regarding the SSc subtype (limited vs diffuse), autoantibodies status (anti-centromere, anti-SCL70 and anti-RNA polymerase III), and the presence or absence of digital ulcers were collected <h3>Results:</h3> Lower levels of LL37 were observed in SSc vs RA patients (36.79 ng/ml vs 69.54 ng/ml, P&lt;0.05). Levels of LL37 were significantly higher in SSc with one or more digital ulcers vs SSc without digital ulcers (53.97ng/ml vs 23.06ng/ml, p&lt;0.05). No significant differences were found between LL37 levels in RA patients and SSc patients with digital ulcers (69.54ng/ml vs 53.97ng/ml, P=0.37), lower levels were still observed in SSc patients without digital ulcers when compared to RA patients (23.06 ng/ml vs 69.54ng/ml, P&lt;0.05). No significant differences in LL37 levels were observed between the limited and diffuse SSc subtypes (38.37ng/ml vs 32.71ng/ml, P=0.75). Antibodies status did not affect the levels of LL37 in SSc patients. <h3>Conclusion:</h3> The increase in LL37 levels in SSc patients with active digital ulcers compared to patients without digital ulcers may indicate that LL37 has a role in local inflammation and could be used as a possible biomarker for digital ulcers development in SSc. <h3>REFERENCES:</h3> [1] Takahashi, T., et al., <i>Cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors.</i> Scientific Reports, 2018. <b>8</b>(1): p. 4032. [2] Kahlenberg, J.M. and M.J. Kaplan, <i>Little Peptide, Big Effects: The Role of LL-37 in Inflammation and Autoimmune Disease.</i> The Journal of Immunology, 2013. <b>191</b>(10): p. 4895-4901. [3] Hizal, M., et al., <i>Decrease of LL-37 in systemic sclerosis: a new marker for interstitial lung disease?</i> Clin Rheumatol, 2015. <b>34</b>(4): p. 795-8. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1198 COPD OUTCOMES IN INDIVIDUALS WITH SCLERODERMA COMPARED TO GENERAL POPULATION: A POPULATION BASED STUDY
Authors: S. Piplani, V. Jelic, V. R. Bejugam, S. Kong, S. R. Goguri, S. T. Kolli, S. Chaturvedi, P. K. Komminni, G. Jelic, D. Damania, M. Vukelic, M. Radulovic
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Chronic obstructive pulmonary disease (COPD) contributes to 3 million annual deaths. Linked to chronic inflammation and respiratory symptoms, COPD's impact on morbidity and mortality is substantial. Recent research points to autoimmune diseases heightening COPD risk. Among these, scleroderma stands out—a rare autoimmune disorder affecting multiple organs. <h3>Objectives:</h3> To investigate the COPD outcomes in individuals with Scleroderma compared to general population. <h3>Methods:</h3> National Inpatient Database was queried from 2015 to 2019, with Principal Diagnosis of COPD and secondary diagnosis was used for Scleroderma using ICD-10 codes. Data was appended using latest HCUP guidelines. Univariate analysis with student t test and chi square was performed, and a multivariate regression model was created to generate odds ratio adjusting for hospital level confounders and various co-morbidities. P-value of &lt;0.05 was considered significant, and all the analysis was performed using STATA-MP v 14.2. <h3>Results:</h3> Demographic data comparing COPD outcomes in individuals with Scleroderma to the general population reveals significant differences. In the Scleroderma group (n=2100), the mean age is 66.61 years, slightly lower than the general COPD population (n=2538704) with a mean age of 68.18 years (p&lt;0.0001). Notably, Scleroderma patients exhibit a higher proportion of females (83.81% vs. 57.7%, p&lt;0.0001) and diverse racial distribution (p&lt;0.0001). The Charlson Comorbidity Index, ZIP code income, and insurance type also exhibit significant variations (all p&lt;0.0001). Univariate and multivariate analyses, assessing COPD outcomes in Scleroderma individuals, reveal no significant association with mortality, length of stay, total charges, or ventilation. Descriptive statistics indicate marginal differences in outcomes between the two groups, with a slightly higher percentage of deaths and longer length of stay in the Scleroderma cohort. <h3>Conclusion:</h3> The research reported high mortality and morbidity rates in COPD patients suffering from Scleroderma. However, due to the complexity of these conditions, additional research is required to fully comprehend the influence of Scleroderma on COPD.REFERENCES: NIL. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1164 ACCUMULATION OF MEGAKARYOCYTE-DERIVED EXTRACELLULAR VESICLES IN SYSTEMIC SCLEROSIS
Authors: A. Manfredi, N. Maugeri, G. A. Ramirez, A. Capobianco, A. Monno, F. Iannone, S. Franchini
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Vasculopathy, microvascular endothelial cell dysfunction, platelet activation, and interstitial lung disease (ILD) are hallmarks of systemic sclerosis (SSc). Recently, extramedullary thrombopoiesis, involving the adaptation of megakaryocytes (Mks) to stress conditions, has been described in infectious and inflammatory contexts. Activated Mks and platelets both release extracellular vesicles (EVs) and mitochondria. Little is known about Mks activation in SSc. <h3>Objectives:</h3> We investigated whether Mks-derived EVs, detectable in the blood and amenable to analysis in vitro and in vivo, can provide insights into the state of Mk activation in SSc. <h3>Methods:</h3> We examined 35 SSc patients and 25 age- and sex-matched healthy donors (HD). EVs were assessed in platelet-free plasma by flow cytometry, and EVs were purified through sequential ultracentrifugation<sup>[1,2]</sup>. In vitro experiments involved evaluating mitochondria transfer to microvascular primary lung endothelial cells, while lung histology was assessed post-EVs transfer in NSG mice, known for their receptiveness to human tissues. <h3>Results:</h3> Mks-derived EVs and platelet-derived EVs, containing or lacking mitochondria, accumulated in the plasma of SSc patients (see Table 1). The concentration of both total Mks-EVs and mitochondria-containing Mks-EVs was significantly higher in SSc patients with ILD (see Figure 1). Encapsulation into EVs seemed to enhance the horizontal transfer of mitochondria to nucleated cells. In vivo experiments demonstrated that the injection of SSc-EVs, but not purified mitochondria, rapidly induced lung fibrosis. <b>Table 1.</b> *: P&lt;0.05 vs healthy donors; <sup>#</sup>: P&lt;0.05 vs patients with ILD <h3>Conclusion:</h3> The accumulation of plasma Mks-derived EVs may serve as an indicator of lung involvement in SSc patients. Further investigations are needed to understand whether extramedullary Mks indeed contribute to the natural history of the disease. <h3>REFERENCES:</h3> [1] Manfredi AA; et al. Platelet Phagocytosis via P-selectin Glycoprotein Ligand 1 and Accumulation of Microparticles in Systemic Sclerosis. Arthritis Rheumatol. 2022. 10.1002/art.41926. [2] Maugeri N; et al. Platelet microparticles sustain autophagy-associated activation of neutrophils in systemic sclerosis. Sci Transl Med. 2018; 10. 10.1126/scitranslmed.aao3089. <h3>Acknowledgements:</h3> This project is funded by the European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS. <h3>Disclosure of Interests:</h3> <b>None declared.</b>