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Systemic autoimmune and inflammatory disorders (SAID) are underestimated, and potentially life-threatening complications observed in 15-25% of myelodysplastic neoplasms (MDS) and chronic myelomonocytic leukemia (CMML), although pathophysiological links between both types of disorders remain uncertain. In 2020, Beck et al. described VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome (OMIM #301054, defined by the presence of UBA1 mutations, in patients with severe systemic inflammation, chronic fever, 30% of whom had concurrent MDS. VEXAS is typically associated with refractoriness to conventional immunosuppressive therapies (IST) and dismal prognosis, and prospectively evaluated effective treatment strategies remain to be established. In MDS/CMML patients with concomitant SAID, but no UBA1 mutation, we and others observed a high incidence of mutations of the epigenetic regulators TET2 and IDH1/2, whose presence correlated with defects in adaptive T lymphocyte homeostasis. This led us to launch a prospective phase II trial of AZA in patients with MDS/CMML and steroid dependent/refractory SAID. This prospective open-label, single-arm multicenter, phase II study trial (ClinicalTrials.gov identifier: NCT02985190) was sponsored by the Groupe Francophone des Myélodysplasies (GFM, French MDS group). Celgene Corporation supplied the study drug but did not contribute to data collection or analysis. Eligible criteria were: (1) age ≥18 years (2) revised IPSS (IPSS-R) intermediate 2 or high, or IPSS-R low or intermediate-1 with significant cytopenia (i.e., transfusion dependent anemia resistant to erythropoietin-stimulating agents and/or platelets below 30 G/L or below 50 G/L with bleeding, and/or ANC < 0.5 G/l with infectious complications), (3) SAID defined according to usual international criteria for each SAID (all cases were centrally reviewed by expert internists AM and VJ) (4) steroid resistance or dependence of SAID, defined as the inability to decrease the dose of steroids below 15 mg/day during at least 2 months. Thirty patients were included between July 2017 and June 2020 in 18 centers, 29 of whom received at least one cycle of AZA and were considered evaluable. Twelve of the 29 patients (41%) were retrospectively found positive for UBA1 mutation (VEXAS syndrome), while in the remaining cases SAID included inflammatory arthritis (n=6) (rheumatoid arthritis (n=3), undifferentiated (n=2) and psoriasis arthritis (n=1)), unclassified vasculitis (n=3), neutrophilic dermatosis (n=3), unclassified SAID (n=2), systemic lupus erythematosus (SLE), relapsing scleritis and immune thrombocytopenia in one case each. After 6 cycles, 19 patients (66%) had obtained SAID response (including 8 CR and 11 PR), while 10 SAID remained stable and none had progressed. The daily dose of steroids decreased from a median of 50 mg/day (95% CI [40-71]) at AZA onset to 15 mg/day (95% CI [13-31]) (p<0.0001) and 10 mg/day (95% CI [5-10]) (p<0.0001) of prednisone equivalent after 3 and 6 cycles respectively. Median steroid daily dose was lower in SAID responders compared to non-responders after 3 (15 mg/day [12-25] versus 50 mg/day [46-60], p=0.04) and 6 (8 [4-10] versus 33 [21-35], p=0.05) cycles of AZA. Median steroid daily dose did not decrease after 6 cycles of AZA. Thus, in this prospective trial, 66% of MDS/CMML patients with SAID obtained SAID complete or partial response after 6 cycles of AZA. We observed an important and sustained steroid-sparing effect of AZA, with reduction to a median dose below 10 mg/day of prednisone equivalent after 6 cycles. AZA also yielded hematological response in 59% of the patients, and 88% of hematological responders had concomitant SAID response. NIL. NIL. None Declared.

BackgroundRecently, the effectiveness of biological therapies such as inhibitors of tumor necrosis factor-α (TNF-α) and IL-6 receptor (tocilizumab) in TAK patients who were refractory to other immunosuppressive therapies has been reported in several studies. We have recently reported a French nationwide registry that showed quite similar effectiveness of TNF-α antagonists and tocilizumab, with acceptable safety profile and significant steroid sparing effect. A recent phase 3, randomized, double blind, placebo-controlled trial of tocilizumab versus placebo in TAK failed to reach its primary intention-to-treat analysis, but tocilizumab was favored in a secondary per-protocol analysis regarding TAK time to relapse. Besides its role on refractory patients, intravenous tocilizumab was also evaluated in treatment-naïve TAK patients in the French TOCITAKA prospective multicenter open-labeled trial, showing 6-month remission rates of 80%, of whom 54% were in glucocorticoid-free remission at 6 months.ObjectivesIn this large multicenter study, we compared the effectiveness and safety of tocilizumab IV versus SC in 109 TAK patients.MethodsWe conducted a retrospective multicenter study in referral centers from France, Italy, Spain, Armenia, Israel, Japan, Tunisia, and Russia regarding biological-targeted therapies in TAK, since January 2017 to September 2019.ResultsA total of 109 TAK patients received at least 3 months tocilizumab therapy and were included in this study. Among them, 91 and 18 patients received IV and SC tocilizumab, respectively. A complete response (NIH<2 with less than 7.5 mg/day of prednisone) at 6 months was evidenced in 69% of TAK patients, of whom 57 (70%) and 11 (69%) patients were on IV and SC tocilizumab, respectively (p=0.95). The factors associated with complete response to tocilizumab at 6 months in multivariate analysis, only age < 30 years (OR = 2.85, 95% CI 1.14; 7.12; p=0.027) and time between TAK diagnosis and tocilizumab initiation (OR = 1.18, 95% CI 1.02; 1.36; p=0.034). During the median follow-up of 30.1 months [0.4; 105.8] and 10.8 [0.1; 46.4] (p<0.0001) in patients who received tocilizumab in IV and SC forms, respectively, the risk of relapse was significantly higher in TAK patients on SC tocilizumab (HR = 2.55, 95%CI 1.08;6.02; p=0.033). The overall cumulative incidence of relapse at 12 months in TAK patients was at 13.7% (95%CI 7.6; 21.5), with 10.3% (95%CI 4.8;18.4) for those on IV tocilizumab versus 30.9% (95%CI 10.5;54.2) for patients receiving SC tocilizumab. Adverse events occurred in 14 (15%) patients on IV route and in 2 (11%) on SC tocilizumab.ConclusionIn this study, we confirm that tocilizumab is effective in TAK, with complete remission being achieving by 70% of DMARDs-refractory TAK patients at 6 months.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background Data on survival and prognosis factors in incident cohorts are scarce in systemic sclerosis (SStc). To describe survival, standardized mortality ratio (SMR), and prognosis factors in systemic sclerosis (SSc), we analyzed a multicenter French cohort of incident patients and performed a systematic review of the literature and meta-analysis. Methods A multicenter, French cohort study was conducted between January 1, 2000, and December 31, 2013. Patients were followed-up until July 1, 2016. A systematic review of the literature was carried out in MEDLINE and EMBASE up to July 2017. Meta-analysis was performed using all available data on SMR and hazard ratios of prognosis factors. Results A total of 625 patients (493 females, 446 lcSSc) were included. During the study period, 104 deaths (16.6%) were recorded and 133 patients were lost to follow-up. Overall survival rates at 1, 3, 5, and 10 years from diagnosis were 98.0%, 92.5%, 85.9%, and 71.7% respectively in the French cohort. Overall SMR was 5.73 (95% CI 4.68–6.94). Age at diagnosis > 60 years, diffuse cutaneous SSc, scleroderma renal crisis, dyspnea, 6-min walking distance (6MWD), forced vital capacity < 70%, diffusing capacity of the lungs for carbon monoxide < 70%, pulmonary hypertension (PH), telangiectasia, valvular disease, malignancy, anemia, and CRP > 8 mg/l were associated with a poorer survival after adjustment. Eighteen studies (11,719 patients) were included in the SMR meta-analysis and 36 studies (26,187 patients) in the prognosis factor analysis. Pooled SMR was 3.45 (95%CI 3.03–3.94). Age at disease onset, male sex, African origin, diffuse cutaneous SSc, anti-Scl70 antibodies, cardiac and renal involvement, interstitial lung disease, PH, and malignancy were significantly associated with a worse prognosis. Anti-centromere antibodies were associated with a better survival. Conclusions Overall, our study highlights a high mortality rate in SSc patients and confirms previously described prognosis factors related to skin extension and organ involvement while identifying additional prognosis factors such as autoantibody status, telangiectasia, 6MWD, and valvular disease.

Idiopathic inflammatory myositis (IIM) is a group of rare and heterogeneous systemic diseases characterized by clinical muscle weakness and histological inflammation in skeletal muscles. Myositis classification distinguishes dermatomyositis (DM), inclusion body myositis (IBM), immune-mediated necrotizing myopathy (IMNM), anti synthetase syndrome (ASSD) and overlap myositis (OM) [1-2]. Patients with myositis are more likely to die younger than in general population [3]. Cardiovascular events (CVE) are one of the main causes of death during the disease's course [4]. To investigate the occurrence of CVE and their link with features of cardiac involvement in a French myositis population. We conducted a retrospective observational cohort study of patients with a diagnosis of DM, ASSD, IBM, IMNM or OM, from the department of internal medicine in Saint Antoine's hospital, Paris, France, between 1992 and 2020. Demographic and clinical data were collected at diagnosis, at the last follow up visit, and at the first CVE if one happened. Subclinical heart involvement was defined by electrocardiogram abnormality, transthoracic echocardiography abnormality or cardiac MRI abnormality. CVE were defined by the occurrence during the follow up of heart failure, inflammatory myocarditis or admission in resuscitation department. Descriptive, bivariate and survival analysis were performed. Among the 78 patients included, 52 (67%) were women. Thirty three patients (42%) had a DM, 18 (23%) an ASSD, 12 (15%) an OM, 11 (14%) an IMNM and 4 patients (5%) an IBM. Mean age at diagnosis was 49 years. Median follow up time was 72 months. Subclinical involvement was present at diagnosis for 17 (22%) patients; and 14 (21%) patients presented a CVE during the follow up period. Patients with subclinical cardiac involvement at diagnosis were more likely to present a CVE than patients without subclinical cardiac involvement. Three years after the diagnosis, 7 CVE occurred in the subclinical cardiac involvement group (event rate 37.5%; 95% CI 4.92-58.92) and only 1 CVE occurred in the no cardiac involvement group (event rate 1.89%; 95% CI 0-5.48). Time to CVE was significantly different between groups (log rank test p < 0,001, Graph 1). This difference remains significant at 5 years after myositis diagnosis. Patients with subclinical cardiac involvement at myositis diagnosis are more likely to present CVE in the first 5 years of disease than patients without subclinical cardiac involvement. Clinical cardiac involvement is rare at diagnostic, but subclinical cardiac involvement seems to be a more frequent condition. Our results suggest that we should pay more attention to patient with subclinical cardiac involvement at myositis diagnosis, especially in the first years of the disease's course. [1]Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. EULAR/ACR Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and their Major Subgroups. Ann Rheum Dis. déc 2017;76(12):1955‑64. [2]Mariampillai K, Granger B, Amelin D, Guiguet M, Hachulla E, Maurier F, et al. Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies. JAMA Neurol. déc 2018;75(12):1528‑37. [3]Dobloug GC, Svensson J, Lundberg IE, Holmqvist M. Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study. Annals of the Rheumatic Diseases. 1 janv 2018;77(1):40‑7. [4]Dankó K, Ponyi A, Constantin T, Borgulya G, Szegedi G. Long-Term Survival of Patients With Idiopathic Inflammatory Myopathies According to Clinical Features: A Longitudinal Study of 162 Cases. Medicine. janv 2004;83(1):35. [Display omitted] NIL. None Declared.

Systemic sclerosis is a systemic autoimmune disease characterized by vasculopathy (Raynaud phenomena), pulmonary arterial hypertension (PAH), and renal crisis), fibrosis of skin and visceral organs (notably the gut, heart, and lungs), and musculoskeletal inflammation (joints, muscles, and tendons) [1]. Inflammation drives atherosclerosis and contributes to cardiovascular (CV) disease [2]. A few studies have examined the incidence of individual macrovascular manifestations such as myocardial infarction, stroke, peripheral artery disease, and venous thromboembolism [3-4-5]. Our aim to estimate the incidence and the arterial ischemic events and venous thrombosis rates of SSc in our database. We also investigated underlying the classical risk factors for venous thromboembolism (VTE) unprovoked (deep venous thrombosis and pulmonary emboli not associated with cancer, recent surgery, hospitalization, fracture and pregnancy) and ASCVD (myocardial infarction and stroke). In a retrospective cohort of SSc patients between 2005 and 2017, arterial ischemic events (myocardial infarction, ischemic stroke), venous thrombosis, risk Factor (Hyperlipidemia, Smoking, Diabetes, hypertension, abdominal obesity), classical risk factors for venous thromboembolism, as well as cardiac, cutaneous and immunological characteristics were assessed. The study population comprised 212 patients (86 % female) with a diagnosis of SSc. We identified a total of 7 (3%) and 26 (12%) patients have respectively an only arterial ischemic events or venous thrombosis, and 6 (3%) additional patients have both arterial and venous thrombosis, with an event during median 10(5-34) and 6 (0-55) years of follow-up. Venous thrombosis (VT) is present in 26 patients (12 %), active or historic neoplasia is present in 4 patients (15%) of VT. In comparison of patient without VT, 20 patients (11%) have a neoplasia. Arterial ischemic events are also most frequent in female sex n=6 (86 %) with all patients (100%) have a limited sclerosis, antinuclear antibodies and Raynaud phenomena, but no difference with the control group without thrombotic events. The prevalence of most cardiovascular disorders was found to be higher in the SSc with limited sclerosis than in diffuse sclerosis. The tobacco use, alcohol is not associated of increase risk of thromboembolic events. The presence of other autoimmune tissue disorders is not significant (p>0.0003) associated of increase rate among patients with SSc with thrombotic events than without. Further adjustment for medications (aspirin, NSAIDs, glucocorticoids, statins, oral anticoagulants, and platelet inhibitors) and comorbidities yielded results similar to the main analyses, except for ischemic stroke. In this monocentric study, SSc was associated with greater risks of venous thrombosis and ischemic events, with a mortality rate in group with arterial ischemic events. There is no significant statistic difference associated of the classical risk factors of venous thromboembolism, comorbidity and the arterial ischemic events and venous thrombosis in systemic sclerosis. [1]Clements PJ, Hurwitz EL, Wong WK, et al. Skin thickness score as a predictor and correlate of outcome in systemic sclerosis. Arthritis Rheum. 2000; 43:2445–2454 [2]Wollheim FA. Classification of systemic sclerosis. Visions and reality Rheumatology. 2005;44:1212–6. [3]Ranque B, Mouthon L. Geoepidemiology of systemic sclerosis. Autoimmun Rev. 2010;9: A311–8 [4]Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial Fibrillation. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition) Chest. 2008;133(6 Suppl):546S–592S [5]Becker RC, Meade TW, Berger PB, et al. The primary and secondary prevention of coronary artery disease. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition) Chest. 2008;133(6 Suppl):776S–814S NIL. None Declared.

Natural language processing tools are powerful for mining rheumatology databases, extracting patient information directly from clinical notes. However, these algorithms come with a high computational cost and are often not applicable at the scale of very large databases in the temporality of clinical practice. The objective of our study is the automatic detection of clinical documents of interest for a specific clinical question, with low computational cost, to be applied on a database of millions of documents. These sets of documents of interest constitute a pre-screening to allow the development of more complex algorithms. The task was considered as an information retrieval task in French clinical texts. Two different methods were compared. For the first method, we used several state-of-the-art document vector representations: TF-IDF, doc2vec, docBERT and tested if the closest documents are relevant. The second method consists in building a powerful query expansion from a key term entered, its French synonyms from the UMLS and the synonyms found by similarity with the embeddings of the CODER algorithm. These methods are developed and evaluated on a set of 8 and on 20 phenotypes respectively (e.g. “pericarditis in lupus”, etc.). Our database corresponds to 2 million documents from a cohort of patients suffering from four autoimmune diseases: systemic lupus erythematosus, scleroderma, antiphospholipid syndrome, and Takayasu's disease, coming from the AP-HP's data warehouse. Our experience does not support the vector representation model of clinical notes for searching similar patients. However, searching with an advanced synonym search method can lead to very good results without additional burden for the clinician: we achieved a precision (or positive predictive value) of 0.93 [0.90; 0.96] evaluated manually by a physician and a recall (or sensitivity) of 0.78 [0.71; 0.85] evaluated on the basis of the ICD10 codes of the retrieved patients. We propose a new advanced keyword search method with automatic synonym search with very good accuracy and recall performance. [1]Alison Callahan, Vladimir Polony, José D Posada, Juan M Banda, Saurabh Gombar, Nigam H Shah, ACE: the Advanced Cohort Engine for searching longitudinal patient records, Journal of the American Medical Informatics Association, Volume 28, Issue 7, July 2021, Pages 1468–1479, [2]Yuan, Zheng, et al. “CODER: Knowledge-infused cross-lingual medical term embedding for term normalization.” Journal of biomedical informatics 126 (2022): 103983 [3]Gérardin C, Mageau A, Mékinian A, Tannier X, Carrat F, Construction of Cohorts of Similar Patients From Automatic Extraction of Medical Concepts: Phenotype Extraction Study, JMIR Med Inform 2022;10(12):e42379 The authors would like to thank the AP-HP data warehouse, which provided the data and the computing power to carry out this study under good conditions. We would like to thank all the medical colleges, including internal medicine, rheumatology, dermatology, nephrology, pneumology, hepato-gastroenterology, hematology, endocrinology, gynecology, infectiology, cardiology, oncology, emergency and intensive care units, that gave their agreements for the use of the clinical data. None Declared. [Display omitted] Table 1Accuracy and recall results for 13 over 20 queries.QueryAccuracy (on 50 manually-annotated document per query)Recall (comparison with respective CIM10)Number of corresponding documents1“Rheumatoid Arthritis”0.980.73151892“Takayasu”10.9424593“Pericarditis in lupus”0.920.9374904“Kidney transplantation”0.920.98107165“Autoimmune hepatitis”0.80.8527976“Dermatomyositis”1.00.7735107“Idiopathic thrombocytopenic purpura”0.980.8137498“Acute kidney injury”0.860.81157759“Raynaud syndrome”0.980.983190010“HIV”0.900.984358211“Scleroderma”1.00.922419912“Diabetes”0.960.965122413…“Stroke”…0.640.6328162Overall0.93 [0.90; 0.96]0.78 [0.71; 0.85]

VEXAS (Vacuoles, E1 Enzyme, X-linked, autoinflammatory, Somatic) syndrome is a recently described severe adult-onset autoinflammatory disorder mediated by X-linked gene UBA1 somatic mutations, responsible of recurrent fever, skin involvement, chondritis, macrocytic anemia and inflammatory syndrome. Neurological manifestations are rarely described, and predominantly involve peripheral nervous system (PNS) impairment. We report the first central nervous system (CNS) vasculitis in VEXAS syndrome, characterized by headache, cognitive dysfunction and focal signs (cerebellar ataxia). Magnetic resonance imaging (MRI) revealed multifocal white-matter lesions corresponding to recent ischemic strokes, combined with cortical hemorrhagic lesions and gadolinium enhancement of the distal wall vessels. Treatment with methylprednisone, ruxolitinib and tocilizumab led to clinical improvement and a decrease of the inflammatory syndrome. The patient died few months after due to infectious complications. CNS vasculitis, occurring as a manifestation of the systemic auto-inflammatory state of VEXAS syndrome, might be a rare but severe complication. We suggest that it be added to the list of inflammatory vasculopathies. More prospective studies are needed to optimize the treatment.

Background:VEXAS syndrome is an autoinflammatory disease associated with somatic mutations in the UBA1 gene, which is located on the X chromosome, which explains the male preponderance of the disease [1]. Several case reports of females with VEXAS syndrome due to constitutional or acquired X monosomy have been published [2].Objectives:Our aim was to describe a series of female VEXAS from the French VEXAS cohort and to compare the clinical, biological and genetic characteristics of the disease between men and women.Methods:A French national multicenter retrospective study was conducted between November 2020 and September 2023. All cases of VEXAS syndrome confirmed by the presence of a UBA1 mutation were included. Data were collected in a Redcap database by clinicians belonging to the French file of rare autoinflammatory/autoimmune diseases (FAI2R), the French group for the study of vasculitis (GFEV), the French group for myelodysplastic syndromes (GFM), the national reference center for autoinflammatory diseases (CEREMAIA) and/or the French group for immunohaematological diseases (MINHEMON). Statistical analysis was performed witheasymedstat software.Results:The French cohort included 263 patients with VEXAS syndrome, 9 of whom (3%) were women with a mean age of 72.6 (± 10.4) years, which was not significantly different from men (p=0.56). Clinically, the VEXAS syndrome in these 9 women was characterized by the presence of fever (n=8), altered general condition (n=5), neutrophilic dermatosis (n=3), chondritis (n=4), pulmonary infiltrate (n=3) and thromboembolic events (n=1). Comparison with the cohort of 263 men showed no statistically significant difference except for diarrhea (8/263 men vs 1/9 women, p=0.05) and aortitis (7/263 men vs 1/9 women, p=0.04), which were observed more common in women. In the female group, the median CRP was 56 mg/l [22-128]. Myelograms were performed in 8 patients; myeloid vacuoles were reported in five patients. The main features of the myelogram were MDS with a single lineage dysplasia (n=2), MDS with ring siberoblast (n=2), MDS with isolated del(5q) (n=1). Bone marrow karyotype showed X monosomy in 2 patients. Anemia was more profound in females: the mean hemoglobin level at diagnosis was 8.96 g/dl (± 0.96) versus 11.18 g/dl (± 10.1) in males (p=0.02). There was no difference in median corpuscular volume (103.45 (± 8.6) fl in women versus 101.46 (± 8.1) fl in men, p=0.44). UBA1 mutations in women were: p.M14V (n=4), p.M41L (n=2), p.M41T (n=2), other mutation in UBA1 c.T122C (20% detected with new generation sequencing) in one patient. Two additional mutations were identified by next-generation sequencing: ASXL1 (n=2) and U2AF1 (n=1). During follow-up period, only one patient died in the female group.Conclusion:This is the largest series of women diagnosed with VEXAS syndrome and supports what has been reported previously that VEXAS syndrome can affectd women, although less frequently. The main clinical and laboratory features were similar to those reported in the first French series of patients with VEXAS [1]. Anemia was more profound in women than in men. In the presence of a suggestive clinical picture associated with macrocytic anemia and a biological inflammatory syndrome, sequencing of the UBA1 gene should be considered in both females and males especially in those with known Turner syndrome or X monosomia.REFERENCES:[1] Georgin-Lavialle S, Terrier B, Guedon AF, Heiblig M, Comont T, Lazaro E, et al. Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients*. Br J Dermatol 2022;186:564–74.[2] Barba T, Jamilloux Y, Durel CA, Bourbon E, Mestrallet F, Sujobert P, et al. VEXAS syndrome in a woman. Rheumatology 2021;60:e402–3.Acknowledgements:All of the investigators who participated in the French National Vexas Study Group.Disclosure of Interests:None declared.

Background:Autoimmune diseases such as lupus and rheumatoid arthritis have a very significant cardiovascular risk. There are a very few studies that evaluate the cardiovascular risk during primary sjogren syndrome (pSS).Objectives:To evaluate the modifiable cardiovascular risk in primary sjogren syndrome (pSS).Methods:We conducted a retrospective study of all patients fulfilling the 2016 ACR/EULAR classification criteria for pSS. We collected the patient characteristics, age, sex, disease activity …….. current treatments and also modifiable cardiovascular risk factors s (body-mass index, systolic blood pressure, non–high-density lipoprotein cholesterol, current smoking, and diabetes).Results:57 patients were included with a median age of 61.2 [22-87] years, among which 53 (93%) were women.The duration of disease progression of 6.7 years [2-25] and ESSDAI 3.3[0-12].Among 52 (92.8%) with a positive labial salivary gland biopsy (LSGB), 19 (40%) Ssa postive, 10(18%) Ssb positive, 37 (66%) FR positive, and mean gammaglobulin 14.5 g/l[4.6-46.9].About modifiable cardiovascular risk factors; BMI 27[4.6-46.9], with 49% overweight(28/57) and 23%(13/57) obese.High blood pressure in 3%(n=13), tobacco 9%(n=5), 7% diabetes 2 (n=4) and dyslipdémia 46%(n=19).Amoung 36/57 patients with a lipid profile: total cholesterol 4.64 mmol [3.09- 6.65], with 31%(n=11) having hyperCT >5.20 mmol/l, and 30% associated with non-HDL cholesterol level mor than 2.58 mmol/l.Regarding tratements: all patient with hight blood pressure have a treatement, 7%(n=4) oral antidiabetics drug, and 12%(n=7) have a Cholesterol-lowering therapy.Our results confirm the frequency of modifiable cardiovascular risk in primary sjogren syndrome (pSS).Furthermore in ours series, we noted an increase of hypercholesterolaemia but not hight blood pressure[1]. All our patients with hypertension and diabetes mellitus have a treatements, but 36%(4/11) of hypercholesterolaemia not treated, 18% insufficiently treated but 30% of patients had an LDL level more than therapeutic objective for patient swith inflammatorry disease(>1g/l).Conclusion:pSS is associated with an increased risk of cardiovascular risk, and requires multidisciplinary care(cardiologist, rheumatologistic and en endocrinologist).REFERENCES:[1] Cardiovascular disease risk burden in primary sjogren’s syndrome: results of a population-based multicentre cohort study.E Bartoloni et al.The journal of internal médicine 2015.Acknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundSystemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis, and endothelial dysfunction. (1,2) Regulatory T cells (Tregs), which are essential to prevent autoimmunity, showed a decreased frequency and impaired function during SSc. (3,4) Low-dose interleukin-2 (ld-IL2) can expand and activate Tregs, but there are no data in SSc.ObjectivesWe aimed to assess the in vivo biological efficacy of ld-IL2 on Tregs and its safety in patients with SSc.MethodsWe performed an interventional prospective, open-label phase I-IIa study in nine patients with SSc without severe organ involvement (eight patients with limited cutaneous subtype). This trial is a part of the TRANSREG study. All patients received 1 Million International Units (MIU)/day of IL-2 for five days, followed by fortnightly injections for 6 months. The primary endpoint was the change in the relative Tregs blood concentration identified as CD25hiCD127lo/−Foxp3+cells frequencies on day 8 among TCD4+ cells compared with baseline. Laboratory and clinical evaluations (modified Rodnan skin score (mRSS), Clinical Global Impression (CGI) activity and severity scale) were performed between day 8 and month 18.ResultsAt day 8, the primary endpoint was reached with a 1.8(± 0.5) fold increase of Tregs levels among TCD4+ lymphocytes (p= 0.008). Changes in concentration of effector T cells (Teffs) and BCD19+ cells were not statistically significant at day 8 and during maintenance period until month 6.Patients’ clinical assessments were stable throughout the follow-up with no modification on mRSS CGI activity and severity scale. Ld-IL2 was well tolerated, and no serious adverse events occurred.ConclusionLd-IL2 at a dosage of 1 MIU/day for five consecutive days selectively activates and expands Tregs in SSc. Safety data were very encouraging. Phase II efficacy trials are needed to validate therapeutic potential of ld-IL2.References[1]Allanore Y, Simms R, Distler O, Trojanowska M, Pope J, Denton CP, et al. Systemic sclerosis. Nat Rev Dis Primer. 23 avr 2015;1:15002.[2]Denton CP, Khanna D. Systemic sclerosis. Lancet Lond Engl. 7 oct 2017;390(10103):1685‑99.[3]Frantz C, Auffray C, Avouac J, Allanore Y. Regulatory T Cells in Systemic Sclerosis. Front Immunol. 2018;9:2356.[4]Antiga E, Quaglino P, Bellandi S, Volpi W, Del Bianco E, Comessatti A, et al. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br J Dermatol. mai 2010;162(5):1056‑63.Table: Lymphocyte subpopulations analysisDay 1Day 8Treg cellscells/mm3% Among CD4+46.1 ± 15.5121 ± 7.4*6.3 ± 1.410.7 ±.8*Lymphocytescells/mm31307 ± 4581819 ± 14*Treg cells/Teff cells% Among CD4+4.6 ± 1.28.1 ± 1.9*CD3+T cellscells/mm31039 ± 4431463 ± 407*CD4+ T cellscells/mm3782 ± 3531108 ± 369*CD8+ T cellscells/mm3281 ± 156358 ± 150CD19+ B cellscells/mm3159 ± 89140 ± 71CD3-CD56 ± NK cellscells/mm384.8 ± 36.7178 ± 66.5***Data are represented as mean ± sd. Changes between baseline and day 8 were analyzed using by ANOVA for ranked data considering factor time *p<0.05; **p<0.01; ***p<0.001.Figure 1.TRANSREG study designAcknowledgements:NIL.Disclosure of InterestsFrançois BARDE: None declared, Roberta Lorenzon: None declared, Sebastien RIVIERE: None declared, Patrice cacoub Shareholder of: ILTOO Pharma, Michelle Rosenzwajg Shareholder of: ILTOO Pharma, Carlotta CACCIATORE: None declared, Anne Daguenel-Nguyen: None declared, olivier fain: None declared, David Klatzmann Shareholder of: ILTOO Pharma, Arsene Mekinian: None declared.