tbuckley/cabot-search huggingface dataset:
POS0369 IN RHEUMATOID ARTHRITIS, IgA AUTOANTIBODIES ARE PRESENT IN A POLYMERIC STATE; CLUES FOR A MUCOSAL ORIGIN OF THE AUTOIMMUNE RESPONSE?
Authors: A. G. Van Mourik, S. Reijm, A. Bacon, M. A. M. Van Delft, N. Levarht, R. Tjokrodirijo, P. Van Veelen, L. A. Trouw, R. E. M. Toes, K. A. Van Schie, D. Van der Woude
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by B-cells that produce autoantibodies against post translationally modified proteins, such as anti-citrullinated protein antibodies (ACPA), anti-acetylated protein antibodies (AAPA) and anti-carbamylated protein antibodies (a-CarP), together called anti-modified protein antibodies (AMPA). What initially leads to the breach in tolerance and eventually causes rheumatoid arthritis is still unknown, but there are indications, such as changes in the fecal microbiome composition of RA patients, that this tolerance breach takes place in the intestines. <h3>Objectives:</h3> Since antibody responses in the intestines are dominated by IgA, particularly in dimeric form, we set out to characterize the AMPA IgA response in detail. <h3>Methods:</h3> Sera from ACPA-positive RA, ACPA-negative RA and healthy donors were fractionated using size exclusion chromatography, separating proteins on size. Next, all fractions were tested by ELISA for ACPA IgA, AAPA IgA and anti-CarP IgA, as well as total IgM, IgA and IgG. Additionally, AMPA were purified from serum to determine their size by IgA western blot and to investigate the IgA tailpiece by tandem mass spectrometry (MS/MS). Lastly, monoclonal IgA was produced with both tailpiece variants, after which its ability to polymerize was analyzed. <h3>Results:</h3> Intriguingly, of all AMPA IgA, ~70% was found to be polymeric, while total IgA contained only ~20% polymeric IgA. MS/MS analysis furthermore showed a difference in the AMPA IgA tailpiece: in the dimeric fraction ~60% had the complete tailpiece, while in the monomeric fraction this was ~20%. Recombinant IgA with such a complete tailpiece formed up to ~90% polymers, while this was ~40% in IgA with a truncated tailpiece. <h3>Conclusion:</h3> These data indicate that AMPA IgA responses are differently regulated compared to the total IgA antibody response and that the tailpiece might be related to a difference in polymer formation. Moreover, the high abundance of polymeric AMPA IgA suggests a mucosal origin. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Anouk G. van Mourik: None declared, Sanne Reijm: None declared, Alice Bacon: None declared, Myrthe A.M van Delft: None declared, Nivine Levarht: None declared, Rayman Tjokrodirijo: None declared, Peter van Veelen: None declared, Leendert A Trouw Research funding from INOVA diagnostics, part of Werfen, Rene E.M. Toes Research funding from INOVA diagnostics, part of Werfen, Karin A. van Schie: None declared, Diane van der Woude Galapagos, Galapagos.
POS0106 MICROVASCULAR STATUS IN COVID-19 SURVIVORS: A NAILFOLD VIDEO CAPILLAROSCOPY ANALYSIS
Authors: R. Campitiello, A. Sulli, E. Gotelli, E. Hysa, C. Pizzorni, S. Paolino, A. Pinelli, P. Vittoriano Clini, F. Lalli, T. Vojinovic, C. Schenone
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> SARS-CoV-2 infection predominantly affects the respiratory system, however, its notable capacity to induce endothelial cell dysfunction may impact a wide range of organs leading to a broad spectrum of systemic symptoms and complications, as observed in long COVID [1,2]. Nailfold videocapillaroscopy (NVC) is a non-invasive tool able to evaluate microvascular morphology. [3] <h3>Objectives:</h3> The aim of our study was to evaluate microcirculation status in COVID-19 survivors using NVC analysis [4]. <h3>Methods:</h3> Sixty-eight COVID-19 survivors (33 women and 35 men; mean age 58±13 years) after hospitalization (mean days from disease onset 135±82 and mean days from recovery 114±85) underwent NVC examination. The assessment focused on capillaroscopic parameters, such as capillary numerosity, dilated capillaries, giant capillaries, microhemorrhages and capillary ramifications (abnormal shaped/neoangiogenesis). A control group of sixty-one age and sex-matched healthy subjects (HS) (44 women and 17 men; mean age 59±15 years) was enrolled in the study. All patients provided written consent before enrolling into study. <h3>Results:</h3> Data showed a statistically significant lower number of nailfold capillaries (linear millimeter) in COVID-19 survivors when compared to HS (8±0.96 vs 31±0.67; p&lt; 0.01). A trend with increased presence of capillary ramifications (neoangiogenesis) was observed in COVID-19 group, however the result did not reach the statistical significance (26% vs 18%; p= 0.36). A statistically significant lower number of isolated hemosiderin deposits (arised from microhaemorrages) was also present in COVID-19 survivors versus HS (28% vs 59%; p&lt;0.05). No correlations with disease severity were observed. <h3>Conclusion:</h3> SARS-CoV-2 infection was shown to be associated with endothelial damage at NCV analysis in our observational monocentric study. The main alterations observed in our cohort of patients were the capillary loss and the capillary ramifications as sign of neoangiogenesis. This latter microvascular alteration was recently observed significantly more evident in acute COVID patients [5]. Nevertheless, to confirm the presence of loss of capillaries also in large numbers of patients with long COVID further analyses are ongoing. <h3>REFERENCES:</h3> [1] Alunno A et al. RMD Open 2020; 6,e001295. 2. Bonaventura, A. et.al.. Nat. Rev. Immunol. 2021;21:319–329. 3. Cutolo M et al. Nat Rev Rheumatol 2010;6:578–87. 4. Mondini L et al. Diagnostics (Basel). 2023;29;13:1905. 5. Cutolo, M. et al. Reumatismo. 2023;74(4):139-143. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0247 CIRCULATING CD4+CXCR5-PD-1hiICOS+ CELLS ARE ELEVATED INPATIENTS WITH NEWLY DIAGNOSED GIANT CELL ARTERITIS AND ASSOCIATE WITH THE CLINICAL OUTCOME
Authors: M. E. Miranda-Carus, B. Nieto-Carvalhal, I. Monjo-Henry, M. D. C. Uyaguari Morocho, I. Casado-Juárez, A. Balsa, E. De Miguel
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Giant cell arteritis (GCA) is a large-vessel granulomatous vasculitis [1,2]. It is characterized by the presence at the inflamed arterial walls, of activated PD-1+ CD4 T cells [1,2]; this contrasts with observations indicating that a defect of PD-1 signaling is implicated in the pathogenesis of GCA [2]. A population of CD4+CXCR5-PD-1 cells, termed Tph cells, has been described at the inflamed synovium and peripheral blood of patients with Rheumatoid Arthritis [3], and seem to play a pathogenic role in this condition [3]. <h3>Objectives:</h3> To study the frequencies of circulating total Tph (cTph) and activated ICOS+Tph (cICOS+Tph) cells in the peripheral blood of patients with newly diagnosed GCA (nGCA) and examine whether they are related with the clinical outcome. <h3>Methods:</h3> This is a prospective non-interventional study performed on consecutive patients referred to our ultrasound (US) GCA fast track clinic, in whom newly diagnosed GCA (nGCA) was clinically confirmed (2022 ACR/EULAR criteria) over a period of 18 months. Peripheral blood was drawn immediately upon confirmation and after obtaining written informed consent. For each patient, an age and gender-matched healthy control (HC) was also studied. PBMCs isolated by Ficoll- Hypaque gradient were stained with antibodies to CD3, CD4, CD45RA, CD45RO, CXCR5, ICOS, PD-1, and examined by flow cytometry. Patients were treated with standard therapy according to clinical response. <h3>Results:</h3> A total of 60 nGCA patients were included (mean age 82 years, 58 % female). As compared with HC, nGCA patients presented at baseline with an increased frequency of cTph and ICOS+cTph cells. Among the 37 patients who could be followed up for 12 months (the remaining 23 have been diagnosed less than 12 months ago), 15 (40.5%) experienced a relapse (2018 EULAR recommendations; symptoms plus: elevation of acute phase reactants and/or positive US). Interestingly, the baseline frequency of cTph and ICOS+cTph cells had been significantly lower in patients who relapsed as compared with those who did not. <h3>Conclusion:</h3> Newly diagnosed GCA patients demonstrate an increased frequency of cTph and ICOS+cTph cells. Lower basal proportions of cTph and cICOS+cTph cells are associated with relapse. <h3>REFERENCES:</h3> [1] Weyand CM, Berry GJ &amp; Goronzy JJ. J Leukoc Biol. 2018. [2] Zhang H, et al. Proc Natl Acad Sci U S A. 2017. [3] Rao DA, et al. Nature. 2017. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Maria-Eugenia Miranda-Carus Gebro Pharma, BMS, Beatriz Nieto-Carvalhal: None declared, Irene Monjo-Henry: None declared, Mariela del Carmen Uyaguari Morocho: None declared, Irene Casado-Juárez: None declared, Alejandro Balsa BMS, Eugenio De Miguel: None declared.
POS0388 INTEGRATED SOLUBLE PROTEOMICS AND AUTOREACTOMICS: PREDICTING RENAL INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: J. M. Guthridge, R. Lu, B. Jones, C. Guthridge, C. Arriens, J. Merrill, J. A. James
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic lupus erythematosus (SLE), a clinically diverse autoimmune disease, poses challenges in predicting its varied manifestations. While soluble mediator profiles have been used, their predictive accuracy is still limited. <h3>Objectives:</h3> This study aimed to evaluate the potential of soluble human proteomics and autoreactomics in predicting severe SLE manifestations. We included 88 plasmas from 16 healthy controls and 72 SLE patients categorized into groups based on clinical characteristics: Group2 - without renal disease nor anti-nuclear antibodies, Group3 - with anti-dsDNA but no renal disease, Group4 - both anti-dsDNA and renal disease, and Group5 - strong positive anti-RNA autoantibodies with some renal disease. <h3>Methods:</h3> Here, we utilized a high-throughput, sensitive, and highly multiplexed human proteomic assay (Olink Explorer NGS) consisting of 1472 analytes as well as their autoantibody profiles. <h3>Results:</h3> Univariate analysis showed that there are 186 dysregulated proteins in Group2, 398 proteins in Group3, 444 proteins in Group4, and 375 proteins in Group5 compared to controls. Pathway analysis revealed distinct upregulation in toll-like receptor, interleukin-10 response, and cytokine/chemokine signaling in Group3, Group4, and Group5. Notably, interferon-gamma production/signaling was prominent only in group 4 with renal disease. Unsupervised dimensional reduction analysis using UMAP identified four clusters, with cluster 4 comprising patients with renal disease. Cluster 4 showed significantly higher levels of HAVCR2, BST2, IL10, CD300, and IFNG than other clusters. Finally, an iterative feature-selection Random Forest machine-learning model based on HAVCR2, BST2, TNFRSF1B, CXCL9, CD300, and IFNGR was able to predict patients with renal involvement with ~91.0% accuracy. Of interest, HAVCR2 and BST2 are both highly expressed in glomeruli and renal tubules, suggesting the tissue-specific damaging signatures with inflammatory soluble mediators may provide superior manifestation prediction potential. <h3>Conclusion:</h3> The study underscores the importance of a comprehensive approach, combining molecular signatures and inflammatory mediators, for enhanced prediction and monitoring of SLE severity. <b>Table 1.</b> <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0060 COMPLEMENT FACTOR H-RELATED PROTEIN 5 ALLEVIATES JOINT INFLAMMATION AND REDUCES OSTEOCLAST DIFFERENTIATION BY DISRUPTING RANKL-JNK SIGNALING IN COLLAGEN ANTIBODY-INDUCED ARTHRITIS MOUSE MODEL
Authors: Y. J. Oh, J. W. Hur, M. K. Lim, S. H. Kim, W. K. Baek, Y. M. Kang, S. Jo, T. H. Kim, C. N. Son
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Complement factor H-related protein 5(CFHR5), a member of complement factor H, plays an important role in regulating the innate immune system. CFHR5 is known to have an anti-inflammatory effect by binding to complement C3, an inflammatory response protein and activator for osteoclasts. However, the impact of CFHR5 on the autoimmune based on arthritis and its relation to the pathophysiological changes in arthritis and bone loss features remain largely unknown. <h3>Objectives:</h3> The aim of this study was to evaluate the effect of CFHR5 on the aggressive osteoclast and arthritis in the murine Collagen antibody-induced arthritis (CAIA). <h3>Methods:</h3> The effect of recombinant CFHR5 protein (rCHFR5) on arthritis were evaluated in CAIA. The mice were divided into three group and intraperitoneally treated with low dose 0.5 mg/kg, high 1.5 mg/kg, or methotrexate as positive control. Clinical arthritis scores and body weight were measured, and histological changes of ankle joints were performed by Hematoxylin and Eosin (H&amp;E) Toluidine Blue, and Tartrate-resistant acid phosphatase (TRAP) stain. Moreover, to investigate the CFHR5 role, we isolated murine bone marrow-derived macrophages (BMM), induced osteoclasts with rCHFR5 in the presence of Macrophage Colony-Stimulating Factor (M-CSF) and Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) treatments, and subjected to mRNA and protein analysis of RANKL-related singling. <h3>Results:</h3> The therapeutic efficacy of rCFHR5 (0.5 mg/kg) and rCFHR5 (1.5 mg/kg) was compared with that of the vehicle control, which revealed reduction in CAI score of both models. The incidence of arthritis in CAIA was reduced in the rCFHR5 (0.5 mg/kg) low-dose group compared to the vehicle. The rCFHR5-treated CAIA group did not show any significant change in body weight, but histological analysis in hind paw revealed a significant reduction in parameters including synovial hyperplasia, pannus formation, bone erosion, and cartilage destruction in rCFHR5-treated CAIA group compared to control vehicle group. In addition, the expression of proinflammatory cytokine (TNF-α, IL-1α, and IL-6) was dramatically reduced in joint ankle of rCFHR5-treated CAIA group. Mechanically, rCFHR5 decreased osteoclast differentiation of BMM by disrupting RANKL-JNK signaling activation. <h3>Conclusion:</h3> In this study, we demonstrated that rCFHR5 administration attenuated joint inflammation and reduced osteoclasts differentiation in both <i>In vivo</i> and <i>In vitro</i> mouse model, indicating that CFHR5 has an anti-inflammatory effect on arthritis of peripheral joints. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0267 FIBROBLAST ACTIVATION PROTEIN INHIBITOR-POSITRON EMISSION TOMOGRAPHY IN AORTITIS: FIBROBLAST PATHOLOGY IN ACTIVE INFLAMMATION AND REMISSION
Authors: W. Merkt, M. Röhrich, J. J. Rosales, P. Kvacskay, U. Haberkorn, N. Blank, H. M. Lorenz
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Reasons for the relapsing character of large vessel vasculitis (LVV) remain obscure, including the role of fibroblasts, in part due to limited access to biopsies of involved tissue.<sup> 68</sup>Ga FAPI-46 (FAPI)-PET/CT detects activated fibroblasts in vivo. <h3>Objectives:</h3> In this exploratory pilot study, we tested the detection of fibroblast activation in vessel walls using FAPI-PET/CT in LVV with aortitis. <h3>Methods:</h3> 8 LVV patients with aortitis and 8 age- and gender-matched controls were included. Distribution of FAPI uptake was evaluated in the aorta and large vessels. FAPI-uptake was compared to MRI inflammatory activity scores. Imaging results were compared to clinical parameters such as serum inflammatory markers, time of remission and medication. <h3>Results:</h3> Three aortitis patients were clinically active, five in remission. Irrespective of activity, FAPI uptake was significantly enhanced in aortitis compared to controls. Patients in remission had a mean duration of remission of 2.8 years (range 1-4 years), yet significant FAPI uptake in the vessel wall was found. In remitted aortitis, MRI inflammatory scores were close to be negative, while in 4/5 patients visually identifiable FAPI uptake was observed. <h3>Conclusion:</h3> This pilot feasibility study shows significant tracer uptake in the aortic walls in LVV. FAPI positivity indicates ongoing fibroblast pathology in clinically remitted LVV. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> We thank all the physician and staff involved in the treatment of patients. <h3>Disclosure of Interests:</h3> Wolfgang Merkt: None declared, Manuel Röhrich: None declared, Juan José Rosales: None declared, Peter Kvacskay: None declared, Uwe Haberkorn UH has filed a patent application for quinoline based FAP targeting agents for imaging and therapy in nuclear medicine. UH has shares of a consultancy group for iTheranostics., Norbert Blank: None declared, Hanns-Martin Lorenz: None declared.
POS0148-PARE LIVING WITH RA IS AN ART – AWARENESS CAMPAIGN WITH ART EXHIBITIONS
Authors: D. Segers, N. Caeyers, V. De Pourcq
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> People with RA experience a daily struggle living with their disease. They need to be inventive to overcome obstacles that are so obvious for other, 'healthy' people. One such an example is to use a button on clothes. For most people this is routine and nothing to think about. For people with RA, closing a button can be a huge struggle. <h3>Objectives:</h3> <b>To raise awareness</b> around RA and the fact that simple things such as closing a button can be a challenge, RA Liga asked professional as well as amateur artists to create an art piece using the concept of the 'oRAnge button'. With these creations, an exhibition was put together that travelled all over the country. Information moments during the exhibition focused on <b>early diagnosis and living with a rheumatic condition</b>. <h3>Methods:</h3> The 'oRAnge button' has been a symbol for RA for the past five years now. Using this symbol to broaden the knowledge of RA with the general public and to focus on early diagnosis was a logical step. Artists all over the country were asked to create their own masterpiece, keeping in mind the oRAnge button. This call led to 121 pieces of art, from paintings to sculptures, drawings and photo's. 75 artists were involved. With all these works, several exhibitions were planned, including the works but also info moments with lectures and peer contact were scheduled. ORAnge button pins are shared with all visitors to wear as a symbolic way of support. The campaign started in September 2022 and will run until October 2024. <h3>Results:</h3> So far, ten places have been visited, four more are already planned for 2024. There are more to be expected in 2024, we are waiting for some final details. (January 2024). Over 1500 people have seen the exhibition today, we expect at least a 1000 more in 2024. We also experience a large social media coverage, since many of the artists share the campaign and their work via their own channels. Our membership list has grown since the launch of this campaign and we see an increase in people contacting our organisation. This shows more people are aware of RA and we can help people in their RA journey. <h3>Conclusion:</h3> This awareness campaign has put the spotlight on RA in an easy accessible way. We reach the general public with art work, which is an unusual angle. It allows us to go far beyond the rheumatology community. In addition, some of the art work will be sold and the profits will go to our organisation. This gives the project a nice extra touch. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0003-PARE THE INTERACTION BETWEEN RHEUMATOID ARTHRITIS AND THE MENOPAUSE: RESULTS OF A NATIONWIDE PATIENT SURVEY
Authors: D. Walker, S. Petford, J. Begum, S. Matthews, C. Jacklin, S. Robinson
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The effects of the menopause have received a lot of attention in the press recently. Anecdotally patients report changes in their arthritis around the menopause either onset or aggravation of symptoms. Clearly there are hormonal influences on arthritis with the sex difference, onset around times of hormonal change and improvement during pregnancy. We were interested to explore the patient perspective to inform future research and educational need. <h3>Objectives:</h3> To understand the patient experience of going through the menopause in the context of rheumatoid arthritis. <h3>Methods:</h3> A national survey was organised through the national rheumatoid arthritis society (NRAS) using their database of interested patients and online community who self selected as peri menopausal, menopausal or post menopausal. A questionnaire was developed by the steering group seeking responses on the effects of the menopause, changes in the arthritis at the time, use of HRT and any discussions they had had with their healthcare providers. <h3>Results:</h3> A total of 779 people responded during October 2023. Respondents were 95% Caucasian mainly in their 50s with onset of menopausal symptoms in their 40s. 80% responded that their arthritis was worse during the menopause with 10% being much worse. 47% had taken HRT. Of these, 72% had had an improvement in their menopausal symptoms and 30% had a moderate or good improvement in their arthritis symptoms. Of those who had had a pregnancy after they developed arthritis, only 19% had an improvement in their arthritis during the pregnancy but for half of these the arthritis went into complete remission. 92% of respondents had no medical discussion about the menopause. For those who did, this was most frequently with the GP in relation to HRT and osteoporosis. 84% felt that the rheumatology team should have more training about the menopause. General comments were on the confusion in the overlap of symptoms between RA and the menopause and conflicting advice about HRT. Many patients were convinced that there was a link between the onset or aggravation of their arthritis and the menopause. Many commented that the survey was very welcome and more research overdue. <h3>Conclusion:</h3> There is a strong association between the menopause and deterioration of arthritis symptoms. Patients would like much more discussion about the menopause but this is not currently happening. There is a great need for further research to clarify the impact of the menopause on people with arthritis. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>