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BackgroundThe prevalence of salivary glands ultrasound (SGUS) abnormalities in Sjögren’s syndrom (SS) is well described(2). However, the prevalence is still unknown in rheumatic inflammatory conditions such as rheumatoid arthritis (RA).ObjectivesThe main objective of this study was to describe the prevalence of SGUS parenchymal structural abnormalites in patients with RA. Secondary objectives were: i) to study correlation between disease duration and the SGUS OMERACT score and ii) to study correlation between duration of sicca syndrome and the SGUS OMERACT score.Methods561 patients with RA satisfying ACR/EULAR 2010 classification criterias were included in 10 french centers in the prospective cohort BCD, comparing joint ultrasonography to clinical follow-up. Cross sectionnal SGUS examination (parotid and submandibular) was performed in a substudy of this cohort. The new OMERACT-SGUS scoring system(1) was used and clinical, biological, immunological and radiological data were collected.Results100 patients agreed to be included in this substudy of BCD cohort, and a total of 98 SGUS patients data were evaluated (lack of SGUS data for 2 patients). Most patients were women (81%), mean age 59 years, with time from RA diagnosis of 11 years on average. The mean CRP-DAS-28 at baseline was at 3.2 with a third of patients in remission at inclusion. Anti-CCP antibodies or RF was positive in 92 patients (92%). 27 patients (27%) complained of eye dryness and 20 (20%) of mouth dryness. 12 (12%) suffered from both. The levels of self-reported fatigue was higher than in the general group of RA included in the study. Two thirds of patients benefited from csDMARD, with a third treated with bDMARDS. 33 (33%) also benefited from a corticosteroid treatment. Among 98 patients, 22 (22.5%) had at least one salivary gland scored grade 1 or more, this number was reduced to 18 patients (18.4%) when considering only the parotid glands. 7 patients (7.1%) had at least one salivary gland scored grade 2 or more, with a number reduced to 4 patients (4.1%) when considering only the parotids. Only one patient (1%) had a parotid gland scored 3. In the 7 patients presenting significant abnormalities in SGUS (grade 2 or more), 5 patients had either dry eye or dry mouth symptoms (71,4%).ConclusionOur findings suggest that 7% of RA patients present significant SGUS abnormalities according to OMERACT scoring system, associated with clinical sicca syndrome in 71% of cases. There was no significant association between the duration of rheumatoid arthritis and the OMERACT score (Spearman coefficient for correlation -0,028, p = 0,99). There was also no significant association found between the duration of sicca symptoms and the OMERACT score (Spearman coefficient for correlation 0,025, p = 0,89). This study highlights the importance of SGUS assessment in RA sicca patients to improve monitoring and follow-up in routine clinical practice.References[1]Jousse-Joulin S, D’Agostino MA, Nicolas C, Naredo E, Ohrndorf S, Backhaus M, Tamborrini G, Chary-Valckenaere I, Terslev L, Iagnocco A, Collado P, Hernández-Díaz C, Gandjbakhch F, Schmidt WA, Filippou G, Dejaco C, Stradner MH, Mortada MA, Hočevar A, Chrysidis S, El Mardenly G, de Agustín JJ, Thiele R, MacCarter DK, Finzel S, Hanova P, Zabotti A, Glaser C, Alavi Z, Hammenfors DS, Gatineau F, Bruyn GA. Video clip assessment of a salivary gland ultrasound scoring system in Sjögren’s syndrome using consensual definitions: an OMERACT ultrasound working group reliability exercise. Ann Rheum Dis. 2019 Jul;78(7):967-973.[2]Zhang X, Feng R, Zhao J, Wang Y, He J, Liu L, Cheng Y, Yao H, Tang S, Chen J, Zhang S, Zhang Z, Wang Q, He J, Li Z. Salivary gland ultrasonography in primary Sjögren’s syndrome from diagnosis to clinical stratification: a multicentre study. Arthritis Res Ther. 2021 Dec 20;23(1):305.Disclosure of InterestsNone declared

BackgroundDespite a high morbi-mortality rate, there are no definite strategy for subclinical interstitial lung disease (ILD) screening in patients with rheumatoid arthritis (RA).ObjectivesOur objectives were: 1. to identify risk factors for subclinical RA-ILD in a prospective discovery cohort (ESPOIR) 2.to develop a risk score for subclinical RA-ILD and 3. to validate the risk score in an independent replication cohort (TRANSLATE 2).MethodsPatients without pulmonary symptoms from 2 prospective RA cohorts who underwent chest HRCT scans were included. All patients were genotyped for MUC5B rs35705950. A risk score based on independent risk factors for subclinical RA-ILD was developed using multiple logistic regression in the discovery cohort. The risk score was tested for validation in the replication cohort.ResultsDiscovery and replication cohorts included 163 and 89 patients, respectively. Subclinical ILD was detected in 19.0% and 16.9% of the patients, respectively. In the discovery cohort, independent risk factors for subclinical RA-ILD were the MUC5B rs35705950 T risk allele (odds ratio [OR]=3.74; 95% confidence interval [CI] [1.37–10.39], male sex (OR=3.93; 95%CI [1.40–11.39]), older age at RA onset (for each year, OR=1.10; 95%CI [1.04–1.16]) and increased mean DAS28-ESR (for each unit, OR=2.03; 95%CI [1.24–3.42]). We developed a risk score for subclinical RA-ILD with AUC=0.82; 95%CI [0.70–0.94] (sensitivity (Se)=71.0%) and specificity (Sp)=79.6%). The risk score was validated in the replication cohort with AUC=0.78; 95%CI [0.65–0.92] (Se=86.7%, Sp=62.2%).ConclusionOur risk score could help identifying patients at high-risk for subclinical RA-ILD before the onset of pulmonary symptoms.Disclosure of InterestsPierre-Antoine Juge Speakers bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Consultant of: Bristol Myers Squibb, Benjamin Granger: None declared, Marie-Pierre Debray: None declared, Esther Ebstein: None declared, Fabienne Louis-Sidney: None declared, Joanna KEDRA: None declared, Tracy Doyle: None declared, Raphael Borie: None declared, Arnaud Constantin Consultant of: Abbvie, Amgen, Biogen, BMS, Boehringer Ingelheim, Fresenius Kabi, Galapagos, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi, UCB, Viatris, Bernard Combe Consultant of: AbbVie, BMS, Eli-Lilly, Gilead, Janssen, Merck, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, René-Marc Flipo Consultant of: Abbvie, Janssen, MSD and Pfizer. He reports research grants from Abbvie, Janssen, Novartis and Pfizer, Xavier Mariette Consultant of: BMS, Gilead, Janssen, Pfizer, Samsung, UCB, Olivier VITTECOQ: None declared, Alain Saraux: None declared, Guillermo CARVAJAL ALEGRIA: None declared, Jean Sibilia Consultant of: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis, Grant/research support from: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis, Francis Berenbaum: None declared, Caroline Kannengiesser: None declared, Catherine Boileau: None declared, Jeffrey Sparks Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer, Grant/research support from: National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers R01 AR077607, P30 AR070253, and P30 AR072577), The R. Bruce and Joan M. Mickey Research Scholar Fund, Bristol Myers Squibb,Bruno Crestani Speakers bureau: Boehringer Ingelheim, AstraZeneca, Roche, Sanofi, Grant/research support from: MedImmune, Roche, Boehringer Ingelheim, Bruno Fautrel Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Fresenius Kabi, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Philippe Dieudé Speakers bureau: Roche – Chugai, Bristol Myers Squibb, Consultant of: Pfizer, Roche – Chugai, Bristol Myers Squibb, Abbvie, MSD, Grant/research support from: Novartis

Introduction La physiopathologie de la pseudo-polyarthrite rhizomelique (PPR) reste mal comprise et il n’y a pas de mecanisme auto-immun clairement identifie a l’heure actuelle. D’un autre cote, l’augmentation de cytokines pro-inflammatoires a ete bien decrite. Malgre cela, la classification de la PPR en tant que maladie auto-immune ou maladie inflammatoire n’est toujours pas claire. Notre objectif etait d’etudier les marqueurs inflammatoires et auto-immuns dans une population bien caracterisee de PPR debutantes. Patients et methodes Dix-huit patients avec une PPR precoce, non traites et 18 temoins sains (TS) apparies pour le sexe et l’âge ont ete inclus. Les patients faisaient partie du protocole TENOR evaluant l’efficacite du tocilizumab en ouvert. Ils ont recu 3 perfusion de tocilizumab entre l’inclusion et la semaine 12 puis des corticoides de la semaine 12 a la semaine 24. Les leucocytes, neutrophiles, plaquettes, hemoglobine, γ-globulines, IgG, IgA et IgM ont ete compares entre les patients PPR et les TS avant et apres le traitement par tocilizumab dans le groupe PPR. Un large panel d’auto-anticorps depistables en routine a ete realise chez les patients PPR et chez les TS. Resultats L’âge moyen etait de 68 ± 7 et 66 ± 11 ans, et le taux serique moyen de proteine C-reactive etait de 82 ± 16 et 5 ± 2 mg/l pour les patients PPR et les TS, respectivement. A l’inclusion, les leucocytes (p Discussion Les donnees de notre etude soulignent les consequences de l’inflammation marquee dans la PPR. Le seul element orientant vers une possible auto-immunite est l’augmentation des gammaglobulines. Toutefois, cette augmentation peut egalement se voir dans les syndromes inflammatoires marques. De plus, il n’y a pas d’autoimmunite plus marquee chez les patients PPR, en comparaison aux HC, sur un large panel d’auto-anticorps. Il est toutefois possible qu’un mecanisme auto-immun impliquant des antigenes non identifies soit a l’oeuvre dans la PPR. Le lien fort existant entre la PPR et l’arterite a cellules geantes peut faire suspecter un mecanisme auto-immune, mais il est aussi possible que la PPR soit un etat tres inflammatoire qui puisse evoluer vers une vascularite si une composante auto-immune vient s’ajouter chez certains patients. Conclusion Cette etude suggere que la PPR est plus une maladie inflammatoire qu’une maladie auto-immune. Le tocilizumab ameliore tous les marqueurs de l’inflammation. Les patients PPR presentant des γ-globulines elevees repondent plus rapidement au tocilizumab.

Introduction La prise en charge de la spondyloarthrite (SpA) axiale est dans certains cas difficile, tant du point de vue de sa confirmation diagnostique que de la decision therapeutique. Chez certains patients, des pathologies autres que la SpA sont susceptibles d’influencer son evaluation clinique. La dysplasie acetabulaire (DA) constitue une anomalie frequente de l’architecture de la hanche, pour laquelle plusieurs etudes ont montre qu’elle peut etre responsable de symptomes douloureux. L’objectif de cette etude ancillaire de la cohorte DESIR etait de determiner si l’identification d’un phenotype de DA est associee a la presence d’une douleur de hanche a l’examen clinique chez les patients presentant une lombalgie inflammatoire recente evocatrice de SpA axiale, pouvant alors constituer une source de confusion lors de l’evaluation des patients. Patients et methodes Cette etude a ete conduite a partir des donnees de la cohorte prospective DESIR, dans laquelle ont ete inclus des patients âges de 18 a 50 ans, presentant une lombalgie inflammatoire recente evocatrice de SpA axiale. L’evaluation radiographique de la DA a ete realisee par l’intermediaire d’une double lecture (DG et GP), a partir des radiographies de bassin de face obtenues lors de la visite d’inclusion. Pour chaque parametre d’evaluation de la DA, la moyenne des mesures faites par chaque lecteur a ete prise pour reference. Les parametres qui ont ete mesures et les valeurs limites correspondantes retenues pour definir la DA etaient : l’angle de Tonnis (> 12°) ; l’angle acetabulaire (> 45°) ; l’angle VCE–Vertical Center Edge - ( Resultats La prevalence globale de la DA etait de 21,9 % (139/636). Elle etait de 26,4 % chez les femmes (90/341) et de 16,6 % (49/295) chez les hommes. A l’exception d’une proportion plus elevee de femmes, il n’a pas ete mis en evidence de difference significative entre les patients avec DA et les autres participants pour ce qui concerne leurs caracteristiques generales et celles relatives a la SpA axiale (activite de la maladie, impact fonctionnel, caracteristiques radiologiques). La presence d’une douleur de hanche etait rapportee chez 20,9 % (29/139) des patients avec DA versus 11,9 % (59/497) chez les autres participants (p = 0,007). En limitant la definition de la dysplasie a la presence d’un angle VCE anormal, la presence d’une douleur de hanche etait rapportee chez 23,6 % (17/72) des patients avec DA versus 12,6 % (71/564) des autres participants (p = 0,01). Conclusion Parmi les patients presentant une lombalgie inflammatoire recente compatible avec une SpA axiale, la presence d’un phenotype de DA (selon plusieurs definitions) est associee a la constatation clinique d’une douleur de hanche. L’existence d’une DA sous-jacente semble pouvoir constituer un facteur de confusion lors de l’evaluation de l’activite de la maladie et/ou d’une eventuelle atteinte inflammatoire de la hanche dans le contexte de la SpA axiale.

Background:Interstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA) detected in 20% to 60% of patients with RA on high-resolution computed-tomography (HRCT) chest scan and is clinically significant in near 10%. Despite a high morbi-mortality rate, a definite strategy for preclinical ILD screening in patients with RA remains to be determined. To date, several factors have been reported to increase the risk of RA-ILD occurrence (i.e. older age at RA onset, ACPA positivity, male sex, RA disease activity, the MUC5B rs35705950 promoter variant...). However, none of these risk factors has been validated in a prospective cohort of patients with RA. The ESPOIR prospective cohort includes patients aged 18 to 70 years with recent arthritis (less than 6 months) and a definite or probable diagnosis of RA.Objectives:To identify in the ESPOIR cohort factors associated with ILD after at least 10 years of RA duration in order to develop a predictive score to identify patients with preclinical RA-ILD.Methods:An ILD detection by chest HRCT scan was systematically offered to every patient with definite RA after at least 10 years-follow-up. Chest HRCT scans were centrally reviewed by an experienced radiologist. Potential predictors of ILD were prospectively collected from baseline to the date of the HRCT scan, and all included patients were genotyped for MUC5B rs35705950. To take into account repeated measures, trajectories were determined for disease activity, C reactive protein, smoking, treatment exposure (i.e. prednisone, methotrexate [MTX] and biological disease modifying anti-rheumatic drugs [bDMARDs]). A logistic model was used to identify independent predictors for the occurrence of ILD on HRCT scans. Confidence intervals were estimated using sampling methods. A predictive score for preclinical ILD occurrence was developed based on the identified predictors.Results:163 RA patients according to 2010 ACR/EULAR classification criteria, none of whom had pulmonary symptoms, were investigated with a chest HRCT scan (128 women (78.5%), mean RA duration 13.7 ± 1.1 years, age at inclusion 47.6 y/o ± 10.4, mean disease activity score [DAS]-28 during follow up was 3.1 ± 1.0). ILD was detected in 31 patients (19.0%). The MUC5B rs35705950 minor allele frequency (MAF) was 22.2% and 10.0% in the RA-ILD and RA-noILD populations, respectively (OR univariate=2.6 CI95% [1.2-5.5], P=0.01). After logistic regression, independent predictors for preclinical RA-ILD were male sex (OR=3.9 CI95% [1.4-11.4]), older age at RA onset (OR=1.1 per year CI95% [1.0-1.2]), mean DAS-28 score during the follow-up (OR=2.0 CI95% [1.2-3.4]) and MUC5B rs35705950 T risk allele (OR=3.7 CI95% [1.4-10.4]) (Figure 1). No influence of the use of RA-related drugs (prednisone, MTX or bDMARDs) was identified as risk factor. The logistic model could predict preclinical ILD occurrence after 13 years of RA duration with an AUC=0.82 CI95% (0.72-0.91). A predictive score for preclinical RA-ILD based on the 4 identified predictive risk factors was developed (Sensitivity 80%, Specificity 56%).Figure 1.Factors independently associated with preclinical ILD after 13 years of RA durationConclusion:In this cross-sectional study of the prospective ESPOIR cohort, we identified clinical and genetic predictors for ILD after 13 years of RA duration. We developed a predictive score that could improve risk stratification for preclinical RA-ILD and help physicians identify patients with RA in whom a HRCT scan should be performed.Disclosure of Interests:Pierre-Antoine Juge Consultant of: BMS, Benjamin Granger: None declared, Marie-Pierre Debray: None declared, Esther Ebstein: None declared, Fabienne Louis Sidney: None declared, Joanna KEDRA: None declared, Raphael Borie: None declared, Arnaud Constantin Consultant of: Bristol-Meyers Squibb, Chugai, Roche, Abbvie, MSD, Pfizer, and UCB, Bernard Combe Consultant of: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chigai, and Sanofi, Grant/research support from: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chugai, and Sanofi, René-Marc Flipo Consultant of: Bristol-Meyers Squibb, Roche, Chugai, Abbvie, and Pfizer, Grant/research support from: Roche, Chugai, Abbvie, and Pfizer, Xavier Mariette Consultant of: Bristol-Meyers Squibb, GSK, Janssen, Pfizer, and UCB, Olivier VITTECOQ Consultant of: Bristol Myers Squibb, Roche, Chugai, MSD, Novartis, Pfizer, Abbvie, and Lilly, Alain Saraux Consultant of: Roche, Chugai, and Bristol-Meyers Squibb, Grant/research support from: Roche, Chugai, and Bristol-Meyers Squibb, Guillermo CARVAJAL ALEGRIA: None declared, Jean Sibilia Consultant of: Roche, Chugai, Bristol-Meyers Squibb, UCB, GSK, LFB, Actelion, Pfizer, MSD, Novartis, Amgen, Hospira, AbbVie, Sandoz, Gilead, Lilly, Sanofi, Janssen, and Mylan, Francis Berenbaum Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Elli Lilly, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, Caroline Kannengiesser: None declared, Catherine Boileau: None declared, Bruno Crestani Consultant of: Boehringer Ingelheim, Roche, Sanofi, Apellis, Astra-Zeneca, Grant/research support from: MedImmune, Boehringer Ingelheim, Bruno Fautrel Consultant of: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, SOBI, UCB, Grant/research support from: AbbVie, MSD, Pfizer, Philippe Dieudé: None declared

Introduction La pneumopathie interstitielle diffuse (PID) est une manifestation extra-articulaire frequente de la polyarthrite rhumatoide (PR) associee a une forte morbi-mortalite. La prevalence exacte de la PR-PID clinique ou infraclinique varie ainsi selon les etudes entre 20 et 60 % et depend de la methode de depistage et de sa temporalite par rapport au debut de la PR. Recemment, le variant du promoteur de MUC5B rs35705950 a ete associe a la presence d’une PID chez les patients atteints de PR. La cohorte ESPOIR a inclus et suivi des patients âges de 18 a 70 ans souffrant d’une PR recente probable ou certaine. Nos objectifs etaient : – d’estimer la prevalence de la PID infraclinique au sein de la cohorte ESPOIR apres au moins 10 ans d’evolution ; – d’evaluer l’interet du genotypage de MUC5B rs35705950 comme marqueur predictif de survenue d’une PR-PID. Patients et methodes Dans cette etude transversale au sein de la cohorte ESPOIR, un depistage d’une PID par scanner thoracique haute-resolution (HRCT) a ete systematiquement propose aux patients inclus dans ESPOIR apres 13 ans de suivi. Une lecture centralisee des HRCT a ete realisee par un radiologue expert qui a classe les patients en fonction de la presence ou l’absence de PID. En cas de PID, l’extension et l’aspect ont ete evalues. Deux patients issus de la cohorte ESPOIR precedemment decedes d’une PR-PID ont ete inclus dans l’analyse afin d’identifier les facteurs prognostiques. Tous les patients inclus ont ete genotypes pour MUC5B rs35705950. Une regression logistique a ete utilisee afin d’identifier les facteurs collectes a l’inclusion dans ESPOIR et predictifs de la presence d’une PID apres au moins 10 ans d’evolution de la PR. Les intervalles de confiance ont ete estimes par methode d’echantillonnage. Resultats Parmi les 170 patients explores par HRCT [133 femmes (78,2 %), duree moyenne de la PR 13,7 ± 1,1 ans], une PID infraclinique etait detectee chez 31 patients (18,2 %) : 19 femmes (61,3 %), âge moyen 67,9 ± 8,7 ans, âge moyen au diagnostic de PR 54,3 ± 8,6 ans. L’etendue de la PID etait 10 % chez 9 patients (5,3 %). Quatre patients presentaient un aspect de pneumopathie interstitielle commune, 4 patients presentaient un aspect de pneumopathie interstitielle non specifique. Des signes scannographiques de fibrose pulmonaire etaient detectes chez 16 patients (9,4 %). Parmi les europeens caucasiens (n = 160), la frequence de l’allele mineur de MUC5B rs35705950 etait de 26,5 % chez les patients PR-PID et de 8,9 % chez les patients PR-non PID (OR = 6,0 ; IC95 %(1,2–7,2)). Apres regression logistique, les facteurs presents au diagnostic de PR et predictifs de survenue d’une PID a 13 ans etaient le sexe masculin (OR = 2,6 IC95 %(1,0-6,6)), un âge au debut de la PR > 49 ans (OR = 5,2 IC95 %(2,0-15,1)), un nombre d’articulations gonflese >9 (OR = 2,9 IC95 %(1,2-7,2)), le caractere migrateur et non fixe des arthrites (OR = 3,4 IC95 %(1,4-8,7)) et l’allele a risque T de MUC5B rs35705950 (OR = 3,8 IC95 %(1,5-10,1)). Ce modele logistique permettait de predire la presence d’une PID apres au moins 10 ans d’evolution de la PR avec une aire sous la courbe = 0,80 IC95 %(0,72-0,90). Conclusion Dans la cohorte ESPOIR, apres au moins 10 ans d’evolution de la PR, la prevalence de la PID infraclinique etait de 18,2 %. Au diagnostic de PR, en association avec certaines donnees cliniques, le genotypage de MUC5B rs35705950 permet d’ameliorer la stratification des patients a risque de developper ulterieurement une PID.

Introduction L’existence d’un antecedent familial de polyarthrite rhumatoide (PR) constitue l’un des principaux facteurs de risque de developper la maladie. Plusieurs etudes conduites chez des patients presentant une PR etablie ont montre une association entre la presence d’un antecedent familial de PR et certaines caracteristiques de la maladie telles que le statut serologique, l’âge de debut et possiblement le profil de reponse a certains des traitements de fond de la maladie. A ce jour, l’impact d’un antecedent familial de PR dans le contexte particulier de la polyarthrite debutante n’a pas ete etudie. L’objectif de cette etude ancillaire de la cohorte ESPOIR etait de determiner, chez des patients presentant une polyarthrite debutante, l’impact d’un antecedent familial de PR sur la presentation initiale du rhumatisme inflammatoire, le diagnostic final et le devenir a long terme de la pathologie. Patients et methodes Cette etude a ete conduite chez l’ensemble des patients inclus dans la cohorte ESPOIR entre 2002 et 2005. Dans le cadre de cette cohorte prospective, des patients âges de 18 a 70 ans ont ete recrutes sur la base de la presence d’au moins 2 articulations gonflees depuis plus de 6 semaines et moins de 6 mois, l’absence d’utilisation prolongee de la corticotherapie et l’absence de recours prealable a un traitement de fond antirhumatismal. De plus, le diagnostic de PR devait etre considere comme certain ou probable par le rhumatologue referent. Dans le cadre de cette etude ancillaire, les patients ont ete stratifies en deux groupes selon l’identification d’un antecedent familial de PR lors de l’evaluation systematique a la visite d’inclusion. Les donnees concernant la presentation initiale du rhumatisme inflammatoire, le diagnostic final (avec un recul de 2 ans) et l’evolution a long terme (a 5 ans) ont ete comparees entre les deux groupes de patients. Les analyses statistiques ont ete realisees a l’aide du logiciel SPSS, ajustees sur les facteurs de confusion potentiels pour ce qui concerne les variables dichotomiques relatives au devenir des patients. Resultats Cent quinze patients (14,1 %) ont rapporte un antecedent familial de PR. En ce qui concerne la presentation initiale du rhumatisme inflammatoire les patients ayant rapporte un antecedent familial de PR presentaient de facon plus frequente des manifestations extra-articulaires (51,8 % versus 39,6 %, p = 0,01). En ce qui concerne le diagnostic final, les patients ayant rapporte un antecedent familial avaient de facon moins frequente un diagnostic alternatif plausible a la PR d’apres le rhumatologue referent (28,3 % versus 42,1 %, p-ajuste = 0,02). En ce qui concerne le devenir a long terme, le recours a un traitement de fond biologique etait plus frequent chez les patients ayant rapporte un antecedent familial (24,7 % versus 14,8 %, p-ajuste = 0,02), donnees etayees par des analyses supplementaires de survie. Conclusion Cette etude demontre que dans le contexte de la polyarthrite debutante, l’identification d’un antecedent familial de PR constitue une donnee cliniquement pertinente, contenant des informations en rapport avec la certitude diagnostique et l’indication future a un traitement de fond biologique.

Introduction Une homogeneisation des pratiques internationales echographiques des glandes salivaires dans le syndrome de Sjogren comportant un grand nombre de centres et d’echographistes est necessaire pour la realisation des essais internationaux. Patients et methodes Exercice international de reproductibilite echographique des glandes salivaires (SGUS) dans le syndrome de Sjogren (SS). Quatorze echographistes de 7 pays ont evalue 60 images echographiques statiques en mode B (30 parotides et 30 glandes sous-maxillaires). Une formation prealable par pays en visioconference a decrit les anomalies pathologiques des glandes salivaires dans le SS(1) et le nouveau systeme de cotation OMERACT (2). Nous avons evalue l’homogeneite (oui/non), la localisation de zones heterogenes (0 a 3), la presence de bandes fibreuses (0-3), le systeme de cotation OMERACT (0-3), l’OMERACT en items binaires (0-1 contre 2-3) et l’appreciation diagnostique du clinicien (oui/non). La reproductibilite intra-lecteur et inter-lecteur a ete estimee en calculant les coefficients κ de Cohen en utilisant SPSS 25,0 (SPSS Inc., Chicago, IL). L’echographiste le plus experimente etait considere comme le gold standard. Resultats La reproductibilite intra-lecteur du plus experimente etait substantielle pour le systeme de cotation OMERACT (kappa a 0,73). La reproductibilite intra-lecteur des autres echographistes etait moyenne a presque parfaite pour l’homogeneite et le diagnostic, la reproductibilite etait moyenne a substantielle pour les autres items (localisation des zones heterogenes, presence des bandes fibreuses). Pour la cotation OMERACT 5/14 (35 %) echographistes obtenaient une reproductibilite substantielle > a 0,6, 6/14 (42 %) avaient une reproductibilite moderee et 3/14 (21 %) avaient une reproductibilite passable. La reproductibilite inter-lecteurs comparee a l’echographiste le plus experimente, montrait une fiabilite moderee a presque parfaite pour l’homogeneite et le diagnostic, mais seulement passable a moderee pour la cotation OMERACT. En changeant le systeme de cotation OMERACT en items binaires, la fiabilite de l’echographiste le plus experimente etait bonne a 0,65, mais nettement inferieur a celui de l’homogeneite. Discussion Les resultats montrent que le systeme de cotation en mode binaire oui/non concernant l’homogeneite et l’appreciation diagnostique du clinicien basee essentiellement sur le caractere homogene ou non de la glande donnent les meilleurs resultats en terme de reproductibilite. En revanche, pour ce qui est de la nouvelle cotation en semi quantitatif (0-3) de l’OMERACT, les resultats montrent qu’une formation en visioconference permet d’homogeneiser les pratiques mais necessiterait un approfondissement. Conclusion L’homogeneite est l’item le plus fiable, et est tres proche de l’appreciation du diagnostic. Le nouveau score semi quantitatif OMERACT presente en visioconference et defini lui aussi sur l’homogeneite glandulaire a donne des valeurs kappa plus faibles mais reste tres utile pour le diagnostic.

Background:For rheumatologists monitoring patients with various diseases and dealing with multiple scores with different maximum values (9 for RA-DAS, 6.4 for AS-DAS and 60 for PMR-AS) and values thresholds to characterize the different levels of disease activity (low, intermediate and high) can be a tedious task. The same problematic could arise in other specialty than rheumatology. Normalization of these scores seems to be necessary to facilitate daily clinical practice (1).Objectives:To indentify and standardize scores of activity of inflammatory diseases.Methods:We conducted a literature review on activity criteria using both a manual approach and the BIBOT software (2) published in English between 1.1.1975 and 31.12.2018. Within all extracted disease activity scores, we selected those with cut off values in four classes (remission, low, moderate and high disease activity). We used a linear interpolation to map all these disease activity scores to our new score, the AS-135, and developed a smart-phone application to perform the conversion automatically.Results:1068 articles were analyzed by BIBOT, 86 were excluded on the basis of the language used for their writing and 11 were excluded on the basis of their publication date. 599 were selected based on their titles, abstracts and keywords. 108 activity criteria from various fields (rheumatology, dermatology, gastroenterology, psychiatry, neurology and pneumology) were identified, but it is in rheumatology that we find separation into four classes. 10 scores met our inclusion criteria and were implemented in the Android app. These are: DAS28 (ESR), DAS28 (CRP), SDAI, ASDAS (ESR), ASDAS (CRP), ESSDAI, SLEDAI-2K, DAPSA, PMR-AS (ESR) and PMR-AS (CRP). We built the AS135 score modification for each selected score using a linear interpolation of the existing criteria. It was defined on the interval [0,10] and values 1, 3 and 5 were used as thresholds. These arbitrary thresholds are then associated with the thresholds of the existing criteria and an interpolation can be calculated, allowing the conversion of the existing criteria into AS135 criterion. We have finally created a mobile application that allows each user to obtain both the original value of the activity criterion.Conclusion:We have created a mobile application that allows any user to obtain in a simple way the level of disease activity, whatever the criterion used to describe it, since the application returns, in addition to the value of the activity criterion calculated from data returned by the physician, the transformation of this value into AS135 criterion and its interpretation in terms of level of activity of the pathology. The application is now available for Android devices and we plan to start developing a version for iOS devices.References:[1]Saraux L, Devauchelle-Pensec V, Saraux A. Plea for standardization of disease activity scores. Rheumatol Oxf Engl. 2019 Aug 1;58(8):1500–1[2]Orgeolet L, Foulquier N, Misery L, Redou P, Pers J-O, Devauchelle-Pensec V, et al. Can artificial intelligence replace manual search for systematic literature? Review on cutaneous manifestations in primary Sjögren’s syndrome. Rheumatol Oxf Engl. 2019 Aug 31;Disclosure of Interests:None declared

Background Abatacept is a CD152 agonist known to inhibit T cell proliferation but recent data suggest that it could act directly on B cells.1–2 Objectives To demonstrate the effect of Abatacept (versus IgG control) on regulatory functions of B cells on T cell proliferation in an established in vitro co-culture model. To evaluate its role, in vivo, by measuring the regulatory functions of B cells from rheumatoid arthritis patients before and after the Abatacept treatment. Methods Peripheral and tonsilar T cell and B cell from healthy controls were purified. The biotinylation of Abatacept was used to study its binding on T and B cells by flow cytometry and confocal microscopy. A well-established co-culture model between CpG-stimulated B cells and anti-CD3/anti-CD28 stimulated T cells was set up in which Abatacept or an IgG control was added to evaluate any change in B cell regulatory functions. Activation markers (e.g. CD25, CD69, CD40, CD152) and regulation markers (e.g. FoxP3, TGF-β) were assessed by flow cytometry. Similar analysis were also performed on rheumatoid arthritis patients before and three months after Abatacept therapy. All patients gave their informed consent. Results Abatacept increases the inhibition of T cell proliferation by B cells compared to IgG control in the co-culture model (p=0.03). Interestingly, alone, Abatacept does not modify T cell proliferation. This can be explained by the increase in IL-10 and TGF-β producing B cells and the CD152 expression. Abatacept is able to bind B cells at day 0 of co-culture and B and T cells at day 4.5 of co-culture. Abatacept has a direct effect on B cells by increasing the CD25 (p=0.03) and CD152 expression (p=0.02) reflecting a higher activation level. Nevertheless, Abatacept had no direct effect on B cell proliferation. In RA patients, the treatment with Abatacept resulted in an increased regulation of T cell proliferation and this effect is related to a higher percentage of IL-10 secreting B cells 3 months after the therapy (p=0.03). Conclusions In our in vitro and in vivo models, Abatacept has a direct effect on B cells leading to an increase capability of regulation of T cell proliferation which directly linked to higher production of IL-10 and TGFβ. References [1] Gazeau, et al. Rheumatology (Oxford)2016Jun;55(6):1138–40. [2] Carvajal Alegria, et al. Ann Rheum Dis2016Nov;75(11):e73. Disclosure of Interest None declared

Background Lumbosacral transitional vertebra (LSTV) is a congenital anomaly of the lumbosacral transition reported in 16% to 36% of the general population. One study reported low clinical relevance of LSTV in the early diagnosis of axial spondyloarthritis (axSpA), but data remains scarce. Objectives Our objectives were to evaluate the association of LSTV with sacroiliitis on conventional radiographs (CR) and magnetic resonance imaging (MRI) in a population with inflammatory back pain (IBP) suspected of axSpA. Methods Baseline pelvic and lumbar CR of DESIR cohort patients (18–50 years, IBP≥3 months but Results 688 patients with available CR enabling LSTV analysis were studied, 47% were men, mean age was 33 years, 64% fulfilled ASAS criteria. Among the 688 patients 29.1% presented LSTV. Number and percentages of patients with different classes of LSTV are presented in Table I. Patients with LSTV had more often sacroiliitis on CR than patients without, respectively 27% and 19% (p=0.013). Patients with LSTV had more often sacroiliitis on MRI (figure 1) than patients without, respectively 39% and 29% (p=0.019). Presence of fusion on the right transverse process was associated with both right (p=0.001) and left (p=0.001) sacroiliitis on CR. Presence of fusion on the left transverse process was associated with sacroiliitis in CR on both right (p=0.006) and left (p=0.001) sides. Conclusions LSTV is observed in 29.1% of patients from the DESIR cohort, as reported in the literature and is associated with sacroiliitis on conventional radiography and MRI. Further study is mandatory to understand if this is based on mechanical stress or AxSpA and to assess the potential bias of LSTV in axSpA diagnosis. Disclosure of Interest None declared

Introduction Le lupus erythemateux systemique (LES) est une pathologie auto-immune rare dont les lymphocytes B (LB) jouent un role clef. Cependant, l’importance de l’activation lymphocytaire B sur les differents parametres cliniques et l’activite du LES reste a definir. Puisque le taux de chaines legeres libres (CLL) (kappa plus lambda) circulant (demi-vie 2–6 h) reflete l’activation polyclonale des LB, ce parametre a ete mesure. Patients et methodes Dans cette etude retrospective, nous avons selectionne 50 patients issus d’une consultation multidisciplinaire dediee au lupus et qui presentaient un lupus selon les criteres de definition. Pour ces patients, nous avons recueilli les informations suivantes : donnees demographiques, manifestations cliniques detaillees pour chaque organe, biologie standard, bilan immunologique complet (humoral et cellulaire) et l’activite de la maladie (SLEDAI). Les taux de CLL ont ete mesures sur l’automate SPA Plus (The binding site) par methode turbidimetrique avec les coffrets CombiLite (The Binding Site), chez les patients lupiques ainsi que pour 105 temoins sains. Resultats Les niveaux de CLL etaient significativement plus eleves chez les patients lupiques (moyenne : 31,74 ± 20,29) en comparaison du groupe de temoin [moyenne : 17,14 ± 6,88) (test T : p Conclusion Les chaines legeres libres sont augmentees dans le LES montrant une activation polyclonale des LB. Cette elevation semble associee a la presence de certains auto-anticorps et du facteur rhumatoide. Toutefois, ce marqueur apparait peu determinant si l’on considere l’activite ou l’atteinte des organes.

Background Autoantibody (Ab) detection including anti-nuclear Ab (ANA) plus anti-dsDNA/Chromatin Ab and/or anti-Sm Ab is central in the diagnosis and prognosis of systemic lupus erythematosus (SLE) and several methods can be used to detect them. Objectives Our objective was to compare diagnostic accuracy for several anti-dsDNA Ab, anti-chromatin Ab and anti-Sm Ab detection. Methods Accordingly, we compared different methods for anti-dsDNA Ab [indirect immunofluorescence using Crithidia Luciliae (CLIFT), anti-dsDNA by ELISA, anti-dsDNA by chemiluminescence (CLIA; IDS-ISYS, IDS) and anti-chromatin Ab (dsDNA-NCX, Euroimmun)] and anti-Sm Ab by ELISA (Immuno concept) and by CLIA (IDS-ISYS, IDS)]. The evaluation was performed in 49 SLE and 98 autoimmune disease controls including rheumatoid arthritis, scleroderma, vasculitis and Sjogren9s syndrome. Results In SLE patients, Ab sensitivity (and specificity) was 97.9% for AAN, 61.2% (92.9%) for anti-chromatin Ab, 36.7% (93 9%) for anti-dsDNA Ab by CLIA, 32.6% (95.9%) for anti-dsDNA Ab by ELISA, and 30.6% (100%) by CLIFT. For anti-Sm Ab, CLIA improved its detection (sensibility 18.4% versus 8.2% by ELISA; specificity 100% both). The best associations were found for anti-chromatin Ab and CLIFT (sensitivity 67.3% and specificity 91.8%), and for anti-chromatin and anti-Sm Abs by CLIA (sensitivity 53.1% and specificity 95.2%). Several associations were identified, including, for anti-chromatin Ab, articular [Odds ratio (OR)=28,41; p=0,002] and cardio vascular disease [OR=9,47; p=0,032], plus leucopenia [OR=13,72; p=0,049]; and for anti-Sm Ab by CLIA lupus glomerulonephritis [OR =5.0, p=0.05], and pleuropulmonary manifestations [OR =25.3; p=0.004]. Conclusions Combining anti-chromatin Ab detection by ELISA and anti-Sm Ab detection by CLIA contribute to improve the diagnosis and the prognosis of SLE. Disclosure of Interest None declared

Background Conventional antibodies are well described and studied in primary Sjogren syndrome, nevertheless patients can also present unconventional autoantibodies. Objectives The objective of this study was to investigate the prevalence of a large panel of conventional and unconventional autoantibodies (Ab) in a well-characterized population of patients with primary Sjogren9s syndrome (pSS). Methods Two hundred and twenty six pSS patients benefiting from a comprehensive clinical and radiological assessment were recruited. A new technique based on chemiluminescence (ISYS-IDS) was selected, in 44 patients, to assay 17 autoantigens including SSA/Ro (52+60 kDa), SSB/La, dsDNA, centromere, Sm, U1-snRNP, Scl70, Jo1, cardiolipin, β2-GPI, CCP2, PR3, MPO, GBM, transglutaminase (IgA), and deaminated gliadin (IgA&IgG). If positive, the presence of Ab was validated by another technique. The study was completed by the search for anti-nuclear Ab (ANA) on HEp-2 cells and rheumatoid factors (RF) against human and rabbit IgG. Results Search for conventional Ab showed ANA (71.7% at 1:320), anti-SSA/Ro Ab (61.1%), anti-SSB/La Ab (31.0%, all anti-SSA+) and IgM RF (44.2%). The triple Ab association (ANA+SSA+RF) rather than the SSA/SSB association was associated with an earlier diagnosis, an active immunological profile (hypergammaglobulinemia, erythrocyte sedimentation rate) and a salivary gland involvement (lymphocyte infiltration, ultrasonography and enlargement). Three patients out of 44 (6.8%) had unintended Ab in current practice directed against centromere, Jo1, and dsDNA plus IgG deaminated gliadin Ab but without associated clinical signs. Conclusions The ability to combine a wide range of autoantibodies can lead to defining new subgroups of pSS patients for precise disease characterization, patient stratification and response prediction. Disclosure of Interest None declared

Background Abnormalities in B-cell population distribution were recently reported in polymyalgia rheumatica (PMR), which improved with glucocorticoids. Data about cytokine involvement in PMR pathophysiology are scarce and contradictory. Objectives Our objective was to analyze the subsets of lymphocytes and level of cytokines in patients with PMR and to follow their evolution after tocilizumab treatment. Methods The TENOR study [Clinicaltrials.gov (NCT01713842)] was an open labeled prospective trial including patients with recent PMR fulfilling the Chuang criteria. Patients had active disease and were glucocorticoids (GCs) free. Patients with suspected giant cell arteritis were excluded. Patients were treated with tocilizumab infusions (week 0, 4 and 8) without GCs (period 1) and then by low-dose GCs from week 12 to week 24 (period 2). Peripheral blood lymphocyte profiling was performed by multicolor flow cytometry in 18 patients at week (W) 0 (before first tocilizumab infusion), W2, W12 and W24. Cytokine levels were estimated using membrane cytokine array enabling detection of 34 different cytokines. Interleukine (IL) 6 and 10 levels were evaluated by ELISA at W0 and W12. They were compared to 16 sex and age-matched healthy controls (HC). Results At baseline, total lymphocyte (p=0.31), T cell (p=0.46), B cell (p=0.08) and NK cell (p=0.905) levels were similar between PMR patients and HC. Transitional B cells (CD24 high , CD38 high ) and mature-naive B cells (CD24 low , CD38 low ) were lower in patients with PMR than in HC, 3±6 vs 6±6 per mm 3 (p=0.01) and 46±41 vs 92±53 per mm 3 (p=0.01), respectively. After tocilizumab, total lymphocyte count slightly increased (1739±539/mm 3 at W0, 2030±591/mm 3 at W2, 2068±775/mm 3 at W12, and 2031±584/mm 3 at W24, p + T cells and NK cells were unaffected by the treatment. In contrast, both absolute number and proportion of B cells increased between W0 and W12, respectively from 176±105/mm 3 to 260±192/mm 3 (p=0.004) and from 10.1% to 13.0% (p Conclusions The drastic clinical improvement following tocilizumab monotherapy in PMR patients is paralleled by an increase in peripheral blood memory B cells. These observations suggest that B cells are involved in disease pathophysiology, and that IL-6 blockade could restore B-cell homeostasis. Disclosure of Interest None declared

Background Primary Sjogren syndrome (pSS) is an autoimmune disease which may be associated to several systemic manifestations. Neurological manifestations seem to be frequent but prevalence is inconstant in literature (1). Objectives To assess neurological involvement prevalence in a national multi-center prospective cohort and to study epidemiological aspects of neurological involvement. Methods The ASSESS (Assessment of Systemic Signs and Evolution in Sjogren9s Syndrome) cohort is a French, multi-centre, prospective cohort, set up in 2006, including 395 pSS patients fulfilling American- European Consensus Criteria (AECG). Demographic and clinical data were compared between patients with and without neurological manifestations, and between patients with peripheral nervous system (PNS) manifestations, central nervous system manifestations (CNS) and no manifestations. Medical records of 26 patients with CNS manifestations and/or cranial nerve involvement were reviewed by both local investigator and our group to confirm or invalidate the association between pSS and the neurological manifestations. Results Data at inclusion were available for 392 patients. Mean follow-up was 33.8 months. Mean age at inclusion was 58 (±12) years. Mean age at diagnosis was 51 (±12) years. Seventy-four of 392 patients (65 females and 9 males) presented neurological manifestations (18.9%). Sixty-three had PNS manifestations (16%) and 14 had CNS manifestations (3.6%). Most frequent peripheral manifestations were pure sensitive neuropathy (9.2%) and sensory-motor neuropathy (5.3%). Only 2 patients (0.6%) had isolated ganglionopathy. Most frequent central manifestations were cerebral vasculitis (5 patients, 1.3%) and myelitis (4 patients, 1.0%) Patients with neurological involvement had more severe disease according to the ESSDAI scoring system, 8.9 (±6.6) versus 3.9 (±4.8). They had more frequently immunomodulatory/immunosuppressive drugs, 32.4% (24/74) versus 13.8% (44/318) (p=0003). Vasculitis was seen in 21 of 73 patients with neurological manifestations (28.8%) and in 30 of 318 patients without (9.4%) (p Conclusions The prevalence of neurological manifestations in the ASSESS cohort was about 20% and is comparable to data in the literature. Isolated ganglionopathy, which is frequently considered as the most specific neurological manifestation in pSS, was rare ( References Carvajal Alegria G et al. Joint Bone Spine. 2014 Jun 20 Disclosure of Interest None declared