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1. Critères d’évaluation à collecter pour optimiser la prise en charge de routine de la spondyloarthrite axiale : proposition fondée sur des preuves et une rencontre d’experts

Author

Eric Senbel, Martin Soubrier, Cécile Hacquard-Bouder, Françoise Fayet, Maxime Dougados, Laure Gossec, C. Lukas, Anna Molto, Athan Baillet, Philippe Gaudin, René-Marc Flipo, Xavier Romand, Arnaud Pflimlin, Sophie Pouplin, Christophe Hudry, Daniel Wendling, Marjorie Schwartz, Mickael Dalecky, Pascal Claudepierre, and Adeline Ruyssen-Witrand

Subjects
Rheumatology
Abstract

Resume Objectif Proposer une liste de variables a collecter des le diagnostic et tout au long du suivi des patients atteints de spondyloarthrite axiale (SpA axiale) pour optimiser leur prise en charge en routine. Methodes Le processus s’est deroule en plusieurs etapes : (1) estimation de l’interet de 51 variables proposees pour l’evaluation de la SpA axiale via une recherche systematique dans la litterature ; (2) consensus de 78 rhumatologues hospitaliers ou de ville notant chaque variable selon un bareme de 4 points de « Peu utile/Inutile » a « Indispensable » ; (3) consensus sur la frequence minimale d’evaluation des variables selectionnees selon un bareme de 5 points allant de « A chaque consultation » a « Jamais systematiquement ». Resultats La recherche systematique a identifie 14 133 resumes dont 213 ont ete inclus dans la synthese qualitative finale. Les donnees a collecter lors du bilan systematique initial comprenaient cinq questionnaires patient auto-administres, trois variables de l’entretien avec le medecin, deux variables de l’examen physique, deux variables de l’imagerie specifique a la SpA axiale et deux autres examens. La collecte systematique a ete recommandee a chaque visite pour deux variables, deux fois par an pour une variable, une fois par an pour six variables et tous les deux ans pour une variable. Conclusions Cette initiative a utilise des approches fondees sur des preuves et sur un consensus d’experts pour definir un ensemble de base de variables a collecter et a consigner immediatement apres le diagnostic et pendant le suivi de routine des patients atteints de SpA axiale.

Published
2021
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2. COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study

Author

Jérôme Avouac, Elodie Drumez, Eric Hachulla, Raphaèle Seror, Sophie Georgin-Lavialle, Soumaya El Mahou, Edouard Pertuiset, Thao Pham, Hubert Marotte, Amélie Servettaz, Fanny Domont, Pascal Chazerain, Mathilde Devaux, Pascal Claudepierre, Vincent Langlois, Arsène Mekinian, Alexandre Thibault Jacques Maria, Béatrice Banneville, Bruno Fautrel, Jacques Pouchot, Thierry Thomas, René-Marc Flipo, Christophe Richez, Florence Aeschlimann, Christian Agard, Nassim Ait-Abdallah, Jean-David Albert, Didier Alcais, Jean-Sébastien Allain, Yannick Allanore, Blanca Amador-Borreiro, Zahir Amoura, Emma Andre, Anaïs Arbault, Jean-Benoît Arlet, Laurent Arnaud, Denis Arniaud, Herliette Arty-Hue, Lucie Atlan, Alexandra Audemard-Verger, Christine Audoin-Pajot, Victor Audren, Maxime Bach-Bunner, Hélène Bacquet-Deschryver, Brigitte Bader-Meunier, Nathalie Balandraud, Jean-Charles Balblanc, Stéphane Bally, Frédéric Banal, Pierre Barbery, Thomas Barnetche, Audre Barrelet, André Basch, Vincent Baumier, Guillaume Bayer, Sophie Bayle, Catherine Beauvais, Rudie Beinat, Véronique Belin, Rakiba Belkhir, Ruben Benainous, Alexandre Belot, Mohammed Benammar, Mathilde Benhamou, Ygal Benhamou, Ahmed Benmansour, Pascal Bennet, Brigitte Bernoux-Manat, Elise Berthet, Emilie Berthoux, Ewa Bertolini, Adrien Bigot, Aurélia Bisson-Vaivre, Gilles Blaison, Gilles Bolla, Olivier Bonidan, Christine Bonnet, Raphaël Borie, Marie Bossert, Laurence Boudou, Françoise Bouhour, Kévin Bouiller, Bastien Bouldoires, Karima Boussoualim, Eric Bouvard, Regine Brondino, Pierre Buchlin, Laurence Cabantous, Patrice Cacoub, Simon Cadiou, Maurizio Carteni, Aurélia Carbasse, Brice Castel, Pascal Cathebras, Hervé Caumont, Annalisa Celant, Benjamin Chaigne, Benoît Chaillous, Romuald Champy, Agnès Charcot, Pierre Charles, Isabelle Charlot-Lambrecht, Caroline Charpin, Emmanuel Chatelus, Bernard Chaudier, Pascale Chertok, Xavier Chevalier, Maxime Chevreau, Emilie Chotard, Delphine Chu Miow Lin, Gaëlle Clavel, Cyril Clavel-Osorio, Fleur Cohen, Gregory Cohen, Marie-Eve Colette-Cedoz, Nived Collercandy, Antoine Colombey, Chloé Comarmond, Bernard Combe, Céline Comparon, Elodie Constant, Pascal Coquerelle, Justine Corli, Clémence Corre, Nathalie Costedoat-Chalumeau, Marie Couret, Natacha Courvoisier, Fabienne Coury-Lucas, Cécile Coutarel, Fabrice Coutier, Richard Damade, Laurence Daver-Malaterre, Sarahe Dehimat, Michel Delahousse, Emilie Barrois-Delattre, Delphine Denarie, Camille Deprouw, Emanuelle Dernis, Alban Deroux, Renaud Desbarbieux, Elise Descamps, Chantal Deslandre, Marie Desmurs, Jacques Despaux, Marie Desplats, Frédérick Detree, Valérie Devauchelle-Pensec, Robin Dhote, Philippe Dieude, Yannick Dieudonne, Elisabeth Diot, Guillaume Direz, Djamal-Dine Djeddi, Sarah Douvier, Béatrice Drouet, Catherine Duc, Angélique Ducornet, Carine Dufauret-Lombard, Alain Duhamel, Cécile Dumaine, Anne-Elisabeth Dumel, Chantal Dumoulin-Richez, Agnès Duquesne, Géraldine Durand, Mariane Durandin-Truffinet, Pierre-Marie Duret, Maïka Duval, Mikaël Ebbo, Esther Ebstein, Andra Economu-Dubosc, Stéphanie Emilie, Romain Euvrard, Philippe Evon, Sylvie Fabre, Dorothée Fagedet, Meryem Farhat, Marion Fauconier, Jacques Fechtenbaum, Renaud Felten, Fanny Fernandes, Nicole Ferreira-Maldent, Elodie Feurer, Amandine Fichet, Françoise Flaisler, Nans Florens, Violaine Foltz, Elisabeth Fontanges, Jennifer Foret, Anne-Claire Fougerousse, Anne Fouque-Aubert, Catherine Foutrier-Morello, Hélène Francois-Pradier, Léa Frantzen, Pierre Fritz, Antoine Froissart, Jean Fulpin, Piera Fuzibet, Francis Gaches, Laurence Gagneux-Lemoussu, Mélanie Penhoat-Gahier, Joris Galland, Frédérique Gandjbakhch, Nicole Garnier, Thomas Garraud, Jean-François Garrot, Romain Gastaldi, Véronique Gaud-Listrat, Maud Gauthier-Prieur, Dana Georgescu, Nathalie Gerard, Elisabeth Gervais, Christelle Gibert, Eric Gibert, Ghislaine Gill, Jérôme Gillard, Mélanie Gilson, Pauline Gimonnet, Jeanine-Sophie Giraudet-Le Quintrec, Aude Giraud-Morelet, Baptiste Glace, Camille Glanowski, Bertrand Godeau, Bruno Gombert, Camille Gonnet-Gracia, Tiphaine Goulenok, Philippe Goupille, Olivier Gourmelen, Sophie Govindaraju-Audouard, Franck Grados, Martine Grall-Lerosey, Bruno Grardel, Anne Grasland, Gilles Grateau, Monica Groza, Constance Guillaud, Séverine Guillaume, Caroline Guillibert, Xavier Guillot, Philippe Guilpain, Aline Gury, Marie-Hélène Guyot, Cécile Hacquard-Bouder, Marie-Noelle Havard, Jean-Pierre Hellier, Pascal Hennequin, Basile Henriot, Julien Henry, Véronique Hentgen, Marion Hermet, Muriel Herasse, Julie Hernandez, Miguel Hie, Pascal Hilliquin, Olivier Hinschberger, Ambre Hittinger-Roux, Jan Holubar, Christophe Hudry, Serge Huguenel, Clara Jaccard, Jean-Michel, Jacquemier, Bénédicte Jamard, Catherine Jan, Sylvie Jean, Mathieu Jouvray, Pierre-Antoine Juge, Laurent Juillard, Denis Jullien, Anna Kabala, Abdelkrim Kabchou, Ludovic Karkowski, Françoise Karman, Farid Kemiche, Jérémy Keraen, Pierre Kieffer, Isabelle Kone-Paut, Abdeldajallil Koreichi, Marie Kostine, Sylvain La Batide Alanore, Pierre Lafforgue, Sophie Lahalle, Marc Lambert, Isabelle Lambrecht, Sylvain Lanot, Aurélia Lanteri, Jean-Paul Larbre, Augustin Latourte, Christian Lavigne, Sophie Le Guen Guegan, Guillaume, Le Guenno, Diane Leguy, Agnès Lebrun, Emmanuel Ledoult, Nathalie Legoupil, Erick Legrand, Charlotte Lejeune, Olivier Leloire, Christophe Leroux, Rémi Leroy, Marie Leroy-Gouix, Tifenn Leturcq, Amélie Leurs, Céline Leveque-Michaud, François-Xavier Limbach, Frédéric Liote, Anne Lohse, Pierre Lozac'h, Virginie Lucas, Aurélie Madelon, Nadine Magy-Bertrand, Matthieu Mahevas, Hélène Maillard, Thibault Maillet, Sandrine Malochet-Guinamand, Quentin Mangon, Sylvie Marchou-Lopez, Nathalie Margarit, Thierry Marhadour, Xavier Mariette, Claire Martin, Alexis Mathian, François Maurier, Frédéric Maury, Betty Mazet-Guillaume, Arnaud Mazouyez, Hassan Mazyad, Nadia Mehsen-Cetre, Ulrich Meinzer, Isabelle Melki, Laurent Messer, Corinne Miceli, Martin Michaud, Catherine Michel, Matthias Michel, Mathilde Michon, Anne-Marie Milesi-Lecat, Anna Molto, Marie Moly, Olivier Moranne, Gautier Morel, Hugo Morel, Jacques Morel, Franck Morin, Laurence Moulinier, Guillaume Moulis, Bertrand Moura, Minh Nguyen, Sabine Nicolas-Vullierme, Hubert Nielly, Gaétane Nocturne, Aurore Nottez, Henri-Olivier Ollagnon, Isabelle Pacaud-Vitoux, Anne Pagnier, Caroline Paris, Antoine Parrot, Tristan Pascart, Yasmina Pascaud-Mansour, Lætitia Paulin, Stephan Pavy, Laurent Perard, Yves-Marie Pers, Micheline Pha, Maud Pichon, Audrey Pierreisnard, Gabrielle Pizana, Sylvaine Poignant, Elsa Poix, Agnès Portier, Antoine Poulet, Samira Plassard, Grégory Pugnet, Déborah Puyraimond-Zemmour, Pierre Quartier-Dit-Maire, Marion Quenet, Viviane Queyrel, Loïc Raffray, Philippe Remy, Myriam Renard, Jessica Rene, Sabine Revuz, Bénédicte Rey, Gaëlle Richard-Colmant, Etienne Riviere, Sébastien Riviere, Sophie Robin, Julien Rohmer, Isabelle Roitg, Mélanie Romier, Michel Rolland, Mélanie Roriz, Carole Rosenberg, Linda Rossi, Olivier Roth, Sid-Ahmed Rouidi, Mathilde Roumier, Mickaël Rousiere, Clémentine Rousselin, Bénédicte Rouviere, Christian Roux, Fabienne Roux, Marielle Roux, Nicolas Roux, Diane Rouzaud, Sylvie Rozenberg, Isabelle Sacco, Fatiha Sadji, Laurent Sailler, Carine Salliot, Jean-Hugues Salmon, Alain Saraux, Jean Schmidt, Julie Seguier, Jérémie Sellam, Eric Senbel, Thomas Sene, Patricia Senet, Pascal Seve, Aurélie Sicaud, Perrine Smets, Vincent Sobanski, Christelle Sordet, Elisabeth Sornay-Rendu, Odile Souchaud-Debouverie, Lætitia Sparsa, Lionel Spielmann, Sarah Steib, Chloé Stavris, Catherine Straus, Victor Strotz, Paulina Szafors, Séverine Taffignon-Clave, Justine Simoens, Claire Theillac, Nora Tenenbaum, Benoît Thomachot, Nathalie Tieulie, Soizic Tiriau, Alice Tison, Eric Toussirot, Ludovic Trefond, Sophie Trijau, Sébastien Trouillier, Anne-Priscille Trouvin, Marie-Elise Truchetet, Marc Ulrich, Jacques Vaquier, Eric Veillard, Laurent Veillon, Guillaume Vial, Jean-François Viallard, Judith Victor, Claire Vidon, Mathias Vidon, Camille Vigne, Alexandre Virone, Ursula Warzocha, Daniel Wendling, Claude Werle, Cécile Wibaux, Alexandra Willems, Michel Wisniewski, Juliette Woessner, Bernadette Xerri-Campano, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Tourcoing, Centre Hospitalier René Dubos [Pontoise], Assistance Publique - Hôpitaux de Marseille (APHM), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Intégrative du Tissu Osseux (LBTO), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Pitié-Salpêtrière [AP-HP], Groupe Hospitalier Diaconesses Croix Saint-Simon, Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Bordeaux [Bordeaux], Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie intégrative du tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Service de rhumatologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CH Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Hopital Réné Dubos, Université Paris 1 Panthéon-Sorbonne - UFR Science Politique (UP1 UFR11), and Université Paris 1 Panthéon-Sorbonne (UP1)

Subjects
medicine.medical_specialty, Immunology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, immune system diseases, law, hemic and lymphatic diseases, Internal medicine, Clinical endpoint, Immunology and Allergy, Medicine, 030212 general & internal medicine, 030203 arthritis & rheumatology, business.industry, Hazard ratio, Odds ratio, Articles, medicine.disease, Intensive care unit, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Rheumatoid arthritis, Cohort, Rituximab, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study, medicine.drug
Abstract

Summary Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. Findings Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66–6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46–0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55–3·19, p=0·53). Interpretation Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. Funding None.

Published
2021
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3. Data to be collected for an optimal management of axial spondyloarthritis in daily practice: Proposal from evidence-based and consensual approaches

Author

Xavier Romand, Sophie Pouplin, Martin Soubrier, Adeline Ruyssen-Witrand, Daniel Wendling, Pascal Claudepierrec, Laure Gossec, C. Lukas, Marjorie Schwartz, Athan Baillet, Philippe Gaudin, Maxime Dougados, Cécile Hacquard-Bouder, Arnaud Pflimlin, Eric Senbel, Christophe Hudry, Anna Molto, Mickael Dalecky, René-Marc Flipo, Françoise Fayet, Centre Hospitalier Universitaire [Grenoble] (CHU), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Hôpital Roger Salengro [Lille], Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 4 : ECaMO - Épidémiologie clinique appliquée aux maladies rhumatismales et musculo-squelettiques (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Rhumatologie [CHU de Montpellier], CHU Montpellier, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Rhumatologie [CHU Gabriel-Montpied], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), and Rheumatologist

Subjects
Diagnostic Imaging, medicine.medical_specialty, Consensus, Evidence-based practice, MESH: Spondylarthritis, Physical examination, Comorbidities, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, MESH: Rheumatologists, Surveys and Questionnaires, Daily practice, Spondylarthritis, Spondyloarthritis, Humans, Medicine, 030212 general & internal medicine, Axial spondyloarthritis, MESH: Consensus, MESH: Surveys and Questionnaires, 030203 arthritis & rheumatology, Core set, MESH: Humans, medicine.diagnostic_test, business.industry, MESH: Diagnostic Imaging, Optimal management, Management, Variable (computer science), [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Scale (social sciences), Family medicine, Rheumatologists, business
Abstract

Objective To propose a list of variables to be collected right after the diagnosis has been made and during the follow-up of patients with axial spondyloarthritis (ax-SpA) for an optimal management in daily practice. Methods The process comprised (1) the evaluation of the interest of 51 variables proposed for the assessment of ax-SpA by means of a systematic literature research; (2) a consensus process involving 78 hospital-based or office-based rheumatologists, considering the collection of each variable in a 4 grade scale from “not very useful/useless” to “mandatory”; (3) a consensus on the minimum interval of time for periodic assessment of the selected variables on a 5 grade scale from “at each visit” to “never to be re-collected”. Results The systematic literature research retrieved a total of 14,133 abstracts, of which 213 were included in the final qualitative synthesis. Data to be collected at the initial systematic review comprised 5 patient's self-administered questionnaires, 3 variables of the physician's interview, 2 variables of the physical examination, 2 variables of the specific ax-SpA imaging and 2 other investigations. Two variables were recommended to be systematically collected at each visit, 1 variable twice a year, 6 variables yearly and 1 variable every 2 years. Conclusions Using an evidence-based and an expert consensus approaches, this initiative defined a core set of variables to be collected and reported right after the diagnosis and during follow-up of patients with ax-SpA in daily practice.

Published
2020
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4. HLA-B27 heavy chain homodimers are expressed in HLA-B27 transgenic rodent models of spondyloarthritis and are ligands for paired Ig-like receptors

Author

Helen C. Bodmer, Maxime Breban, Lucy A. Bird, Cécile Hacquard-Bouder, Paul Bowness, Andrew J. McMichael, Hiromi Kubagawa, Matthew Roddis, and Simon Kollnberger

Subjects
musculoskeletal diseases, medicine.drug_class, Transgene, Recombinant Fusion Proteins, Immunology, Cell, Mice, Transgenic, Biology, Monoclonal antibody, Ligands, Transfection, Cell Line, Animals, Genetically Modified, Mice, Biopolymers, Spondylarthritis, medicine, Immunology and Allergy, Animals, Biotinylation, Spondylitis, Ankylosing, Receptors, Immunologic, skin and connective tissue diseases, Receptor, HLA-B27 Antigen, Mice, Knockout, Tumor Necrosis Factor-alpha, Macrophages, Antibodies, Monoclonal, Dendritic Cells, Molecular biology, Precipitin Tests, Lymphocyte Subsets, Rats, Disease Models, Animal, medicine.anatomical_structure, Cell culture, biology.protein, Tumor necrosis factor alpha, Antibody, beta 2-Microglobulin, Dimerization, Protein Binding
Abstract

HLA-B27 transgenic rats and strains of HLA-B27-transgenic β2-microglobulin (β2m)-deficient mice develop a multisystem inflammatory disease affecting the joints, skin, and bowel with strong similarity to human spondyloarthritis. We show that HLA-B27 transgenic mice and rats express HC10-reactive, β2m-free HLA-B27 homodimers (B272) and multimers, both intracellularly and at the cell surface of leukocytes, including rat dendritic cells. Fluorescent-labeled tetrameric complexes of HLA-B27 homodimers (B272 tetramers) bind to populations of lymphocytes, monocytes, and dendritic cells. The murine (and probably rat) paired Ig-like receptors (PIRs) are ligands for B272. Thus, B272 tetramers stain RBL cells transfected with murine activating PIR-A4 and inhibitory PIR-B receptors. Murine PIR-A and -B can be immunoprecipitated from the RAW264.7 macrophage cell line, and murine PIR-A can be immunoprecipitated from the J774.A1 line using B272. B272 tetramer staining corresponds to the distribution of PIR expression on lymphoid and myeloid cells and on murine macrophage cell lines. B272 can induce TNF-α release from the J774.A1 macrophage cell line. The binding of B272 to PIR is inhibited by HC10, an mAb that ameliorates arthritis in HLA-B27+ β2m−/− mice. The expression and PIR recognition of B272 could explain the pathogenesis of rodent spondyloarthritis.

Published
2016
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5. Two HLA–B27 alleles differently associated with spondylarthritis, B*2709 and B*2705, display similar intracellular trafficking and oligomer formation

Author

Claudine André, Benoit Giquel, Aïcha Cherfa, Céline Denais, Cécile Hacquard-Bouder, Maria-Sole Chimenti, Maxime Breban, Sophie Carmouse, and Ingrid Fert

Subjects
Yellow fluorescent protein, Protein Folding, DNA, Complementary, Transfection, HeLa Cells, Humans, HLA-B27 Antigen, Recombinant Fusion Proteins, Flow Cytometry, Reverse Transcriptase Polymerase Chain Reaction, Plasmids, Spondylarthritis, Immunology, Human leukocyte antigen, Biology, Flow cytometry, Rheumatology, Complementary, medicine, Immunology and Allergy, Pharmacology (medical), medicine.diagnostic_test, Endoplasmic reticulum, DNA, Cell biology, Settore MED/16 - Reumatologia, Biochemistry, Cytoplasm, biology.protein, Protein folding, Intracellular
Abstract

Objective To examine whether and to what extent the intracellular trafficking features of HLA–B*2705, which is associated with the development of spondylarthritis (SpA), differ from those of HLA–B*2709 and HLA–B*0702, which are not associated with SpA. Methods HeLa cells were transfected with complementary DNA encoding for HLA–B proteins fused to Renilla luciferase or yellow fluorescent protein. The subcellular distribution of properly folded and unfolded/misfolded HLA–B proteins was examined by flow cytometry and confocal microscopy of cells labeled with ME1 and HC-10 antibodies, respectively. HLA–B/HLA–B interactions were monitored in endoplasmic reticulum (ER)– and plasma membrane–enriched subcellular fractions, by bioluminescence resonance energy transfer (BRET). Results All 3 HLA–B alleles displayed a similar distribution pattern (properly folded heavy chain at the cell surface, unfolded/misfolded proteins only in the cytoplasm). By means of BRET, we provided evidence that both HLA–B*2705 and HLA–B*2709 formed more oligomers in the ER and the plasma membrane than did HLA–B*0702. The propensity of HLA–B*2705 to form oligomers in the ER was partly attributable to residue Cys67 of the molecule. For all 3 alleles, increased expression of HLA–B proteins was associated with intracytoplasmic accumulation of unfolded/misfolded proteins and intracellular vesicles, probably corresponding to expanded ER–Golgi intermediate compartments, in which these proteins accumulated together with the stress sensor BiP. Conclusion Our results suggest that the difference in disease susceptibility conferred by HLA–B*2705 and HLA–B*2709 cannot be explained by their different propensity to form dimers or misfolded proteins, thus presumably implicating other, still unknown factors.

Published
2007
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6. Modèles animaux de spondylarthropathies liés au HLA-B27 : où en est la recherche ?

Author

M. Ittah, Maxime Breban, and Cécile Hacquard-Bouder

Subjects
musculoskeletal diseases, Animal model, Rheumatology, Biology, Molecular biology
Abstract

Resume La molecule HLA-B27 est fortement associee aux spondylarthropathies, maladies inflammatoires chroniques affectant le squelette mais aussi l'intestin et la peau. Les raisons de cette association ont largement ete etudiees, mais restent, a ce jour encore mal comprises. Les rats transgeniques pour le HLA-B27 developpent spontanement une pathologie proche des spondylarthropathies, dependante de la flore bacterienne et au cours de laquelle est implique le systeme immunitaire. La presence de lymphocytes T CD4 + est indispensable a sa survenue, et les cellules presentatrices d'antigene (CPA) exprimant la molecule HLA-B27 semblent jouer un role dans sa pathogenie. Ces dernieres ont une capacite reduite de stimulation des lymphocytes T naifs resultant d'une diminution de formation des contacts entre les deux types cellulaires. Cette anomalie fonctionnelle des CPA HLA-B27, pourrait perturber le maintien de la tolerance naturelle, particulierement vis-a-vis de la flore intestinale. Chez la souris, deux modeles d'atteinte inflammatoire du squelette lies au HLA-B27 ont ete developpes. La souris ANKENT developpe une enthesite ossifiante du tarse et de la cheville, dont la frequence est augmentee par la presence du HLA-B27. La souris transgenique pour le HLA-B27 et invalidee pour la β 2 -microglobuline endogene, developpe des arthrites des pattes arriere. Dans ce modele, les homodimeres de chaines lourdes de HLA-B27 pourraient etre impliques dans la pathogenie par presentation de peptides exogenes aux lymphocytes T CD4 + .

Published
2006
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7. Animal models of HLA-B27-associated diseases: new outcomes

Author

Maxime Breban, M. Ittah, and Cécile Hacquard-Bouder

Subjects
Mice, Knockout, musculoskeletal diseases, Genetically modified mouse, HLA-B27, Transgene, Arthritis, Rats, Inbred Strains, Inflammation, Biology, medicine.disease, Rats, Animals, Genetically Modified, Pathogenesis, Disease Models, Animal, Mice, Immune system, Rheumatology, Immunology, medicine, Animals, Spondylarthropathies, medicine.symptom, Antigen-presenting cell, HLA-B27 Antigen
Abstract

The HLA-B27 molecule is strongly associated with the spondyloarthropathies, a group of chronic inflammatory diseases, affecting the skeleton, the bowel and the skin. This association has been largely studied, but mechanisms of pathology remain unclear. The HLA-B27 transgenic rats develop a spontaneous disease that strikingly resembles human spondyloarthropathies, dependent of bacterial flora and implicating the immune system. The presence of CD4+ T cells is required, and antigen presenting cells (APC) expressing high levels of HLA-B27 likely play an important role. Indeed, APC are defective in naive T lymphocytes stimulation. This default appears to implicate the APC/T cells contact, and may result in a loss of tolerance toward microbial flora. Two models of skeletal inflammation linked to HLA-B27 have been developed in mice. The ANKENT mice develop a spontaneous ossifying enthesitis affecting ankle and tarsal joints, with increased frequency in the presence of an HLA-B27 transgene. The HLA-B27 transgenic mice lacking endogenous β 2 microglobulin develop arthritis of hind-paws. In this model, homodimers of B27 heavy chains could be implicated in the pathogenesis by presenting exogenous peptides to CD4 + T cells.

Published
2006
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8. Existe-t-il des facteurs qui influencent la concordance entre évaluation clinique et échographie dans la polyarthrite rhumatoïde ?

Author

Maxime Dougados, Sandrine Jousse-Joulib, Maria Antonietta D'Agostino, Christophe Hudry, Laurent Grange, F. Mistretta, Gérard Chalès, Fabien Etchepare, Jean-David Albert, Jérémie Sellam, Isabelle Chary-Valckenaere, Marion Le Boedec, Cécile Hacquard-Bouder, Thierry Marhadour, K. Mari, Philippe Gaudin, Jacques Bentin, Damien Loeuille, Alain Saraux, and Jean-François Ferlet

Subjects
Epidemiology, Public Health, Environmental and Occupational Health
Abstract

Objectifs Evaluer la concordance entre evaluation clinique (C) et echographie (ultrason–US) de la synovite (modes B, D et B + D) dans la polyarthrite rhumatoide (PR) active avant et apres traitement par anti-TNF, puis etudier les facteurs associes a une bonne concordance. Methodes Soixante-seize patients (necessitant une therapie anti-TNF) avec PR active (criteres ACR 1987) ont ete inclus dans une cohorte prospective, multicentrique avec 2 ans de suivi. Pour chaque patient, 38 articulations ont ete evaluees (2 poignets, 2 coudes, 2 epaules, 2 genoux, 10 MCP, 10 IPP, 10 MTP). Le grade de la synovite etait collecte a M0 en utilisant une variable semi-quantitative pour evaluation C (de 0 = pas de synovite de facon certaine a 3 = presence de synovite de facon importante), US mode B (de 0 = pas d’epaississement synovial a 3 = hypertrophie synoviale severe) et mode D (de 0 = aucun flux dans la synoviale a 3 = signaux de vaisseaux dans plus de la moitie de l’aire de la synoviale). Le coefficient kappa a ete determine pour evaluer la fiabilite des variables categorielles (synovite si grade ≥ 1). Les facteurs associes a une bonne concordance ont ete evalues par des analyses uni- et multivariees (tous les facteurs statistiquement significatifs et non correles dans le modele univarie ont ete inclus dans l’analyse multivariee). Resultats La concordance avant traitement anti-TNF entre evaluation C et US (kappa -0,08 a 0,51) ainsi que la concordance entre modes B et D (0,30 a 0,67) etaient variables en fonction du type d’articulation evaluee. La concordance entre C et US etait particulierement faible pour les articulations MTP et les epaules (kappa – mode B : faible DAS28, EVA clinique elevee et positivite des facteurs rhumatoides (FR) ; – mode D : pas d’evolution semi-recente de la PR (2–5 ans), activite moderee de la PR (DAS 3,2–5,1), âge entre 40 et 50 ans, etre une femme. Apres anti-TNF ces facteurs etaient : – mode B : site articulaire (genoux, coudes, MCP 4 et 5, IPP 2 a 5), etre un homme, faible IMC, pas d’evolution semi-recente de la PR (2–5 ans), incapacite moderee sur l’echelle HAQ et faible DAS28 ; – mode D : site articulaire (genoux, coudes, MCP 4 et 5, IPP 1 a 5), faible IMC, evolution recente de la PR, incapacite moderee sur l’echelle HAQ, faible DAS28, evaluation clinique faible et positivite des facteurs rhumatoides (FR). Conclusions La concordance entre les evaluations C et US depend du site articulaire. L’evaluation C sous-estime particulierement la synovite MTP et epaule. Les facteurs associes a une bonne concordance sur les autres sites articulaires sont nombreux et varient en fonction des modes US (les facteurs associes a une bonne concordance C-US modes B et D sont differents) et du traitement (site articulaire, HAQ, IMC faible sont associes a une bonne concordance C-US mais pas avant therapie TNF).

Published
2016
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9. Factors Influencing Concordance Between Clinical and Ultrasound Findings in Rheumatoid Arthritis

Author

Maria Antonietta D'Agostino, Sandrine Jousse-Joulin, Alain Saraux, Thierry Marhadour, Gérard Chalès, Jean-François Ferlet, Jérémie Sellam, Maxime Dougados, Philippe Gaudin, Isabelle Chary-Valckenaere, Fabien Etchepare, Cécile Hacquard-Bouder, Jacques Bentin, Damien Loeuille, Jean-David Albert, Christophe Hudry, Laurent Grange, Marion Le Boedec, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Statistique, RCTS, Lyon, RCTS Lyon, CHU Pontchaillou [Rennes], Clinique Universitaire de Rhumatologie, hôpital Sud, CHU de Grenoble, Assistance publique-Hôpitaux de Paris - Espace éthique (AP-HP Espace éthique), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [Rennes] = Rheumatology [Rennes], Service de Rhumatologie, CHU Brugmann, CHU Brugmann, Belgium, Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], and CHU Pitié-Salpêtrière [AP-HP]

Subjects
Adult, Male, musculoskeletal diseases, medicine.medical_specialty, Pathology, Settore MED/16 - REUMATOLOGIA, Shoulders, Concordance, Immunology, Metatarsophalangeal joints, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Cohen's kappa, Rheumatology, Rheumatoid, Synovitis, Internal medicine, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Prospective Studies, Rheumatoid arthritis, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Physical Examination, Aged, Ultrasonography, 030203 arthritis & rheumatology, business.industry, Tumor Necrosis Factor-alpha, Arthritis, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Middle Aged, medicine.disease, medicine.anatomical_structure, Antirheumatic Agents, Cohort, Female, Joints, business, Kappa
Abstract

Objective.Clinical joint examination (CJE) is less time-consuming than ultrasound (US) in rheumatoid arthritis (RA). Low concordance between CJE and US would indicate that the 2 tests provide different types of information. Knowledge of factors associated with CJE/US concordance would help to select patients and joints for US. Our objective was to identify factors associated with CJE/US concordance.Methods.Seventy-six patients with RA requiring tumor necrosis factor-α (TNF-α) antagonist therapy were included in a prospective, multicenter cohort. In each patient, 38 joints were evaluated. Synovitis was scored using CJE, B-mode US (B-US), and power Doppler US (PDUS). Joints whose kappa coefficient (κ) for agreement CJE/US was < 0.1 were considered discordant. Multivariate analysis was performed to identify factors independently associated with CJE/US concordance, defined as factors yielding p < 0.05 and OR > 2.Results.Concordance before TNF-α antagonist therapy varied across joints for CJE/US (κ = −0.08 to 0.51) and B-US/PDUS (κ = 0.30 to 0.67). CJE/US concordance was low at the metatarsophalangeal joints and shoulders (κ < 0.1). Before TNF-α antagonist therapy, a low 28-joint Disease Activity Score (DAS28) was associated with good CJE/B-US concordance, and no factors were associated with CJE/PDUS concordance. After TNF-α antagonist therapy, only the joint site was associated with CJE/B-US concordance; joint site and short disease duration were associated with CJE/PDUS concordance.Conclusion.Concordance between CJE and US is poor overall. US adds information to CJE, most notably at the metatarsophalangeal joints and shoulders. Usefulness is decreased for B-US when DAS28 is low and for PDUS when disease duration is short.

Published
2013
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10. Can we improve the diagnosis of spondyloarthritis in patients with uncertain diagnosis? The EchoSpA prospective multicenter French cohort

Author

Dominique Monnet, Sandrine Jousse-Joulin, Sandrine Guis, Bertrand Lecoq, Ariane Leboime, Alain Saraux, Philippe Gaudin, Marie Caroline Guzian, Christian Marcelli, Damien Loeuille, Maria Antonietta D'Agostino, O. Judet, Marie Agnes Timsit, Maxime Breban, Alain Blum, Christophe Chagnaud, Philippe Aegerter, Cécile Hacquard-Bouder, Anne-Christine Rat, Isabelle Chary-Valckenaere, Laurent Grange, Roula Said-Nahal, Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Rhumatologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Département d'information hospitalière et santé publique, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Clinique de rhumatologie, CHU Grenoble-Hôpital Sud, Imagerie Guilloz [CHRU Nancy] (Service d'imagerie Guilloz), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Laboratoire Universitaire Santé Environnement Vieillissement, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Physiopathologie, Pharmacologie et Ingénierie articulaires (PPIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Sainte Marguerite], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Groupe de Recherche et d’Étude du Processus Inflammatoire (TIMC-GREPI), AGeing and IMagery (AGIM), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Hôpital Ambroise Paré [AP-HP], Département de Radiologie adultes [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré [AP-HP], Immunologie et Pathologie (EA 2216), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de rhumatologie, CHU Caen, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Imagerie Guilloz [CHRU Nancy] ( Service d'imagerie Guilloz ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] ( Pôle S2R )

Subjects
Male, Settore MED/16 - REUMATOLOGIA, Dactylitis, Cohort Studies, 0302 clinical medicine, Diagnosis, Enthesitis, Prospective Studies, 030212 general & internal medicine, 10. No inequality, Accuracy, HLA-B27 Antigen, ComputingMilieux_MISCELLANEOUS, Ultrasonography, medicine.diagnostic_test, Doppler, Middle Aged, Magnetic Resonance Imaging, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Cohort, Female, France, medicine.symptom, Cohort study, Adult, musculoskeletal diseases, medicine.medical_specialty, Adolescent, Physical examination, Sensitivity and Specificity, Young Adult, 03 medical and health sciences, Rheumatology, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Ultrasound, Spondylarthritis, medicine, Humans, In patient, Sacroiliitis, Aged, 030203 arthritis & rheumatology, business.industry, Power Doppler, Ultrasonography, Doppler, Magnetic resonance imaging, Gold standard (test), medicine.disease, Physical therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

International audience; Power Doppler ultrasound (PDUS) has proved to be a highly sensitive tool for assessing enthesitis in spondyloarthritis (SpA). In patients with a suspected SpA, diagnosis could be improved by detecting enthesitis with PDUS. OBJECTIVE: To evaluate the performance of PDUS for the diagnosis of SpA alone or combined with other clinical, laboratory and imaging findings in patients consulting for a suspected SpA. METHODS: Prospective, multicenter French cohort study (Boulogne-Billancourt, Brest, Caen, Grenoble, Marseille and Nancy). Outpatients consulting for symptoms suggestive of SpA (inflammatory back pain [IBP], arthritis or inflammatory arthralgia [IA], enthesitis or dactylitis [ED], HLA-B27 positive uveitis [B27+U], familiarity for SpA [Fam]) were recruited and followed up for at least 2years. Sample size was set to 500 patients (for estimated prevalence of SpA of 30±5% after 2years). At baseline, patients were submitted to standardized physical examination, pelvic X-ray, sacroiliac joints magnetic resonance imaging (MRI), HLA-B typing, and other tests judged useful for diagnosis. For each patient, a blinded PDUS examination of 14 enthesitic sites was performed at baseline and at years 1 and 2. Patients were planned to be followed during 5years. The diagnosis of SpA ascertained by an experts' committee, blind to PDUS results, after at least 2years of follow-up, with a revaluation of doubtful patients at 5years will be used as gold standard for evaluating the diagnostic performance of PDUS and the best diagnostic procedure by combining PDUS, clinical symptoms and other tests. RESULTS: Between January 2005 and September 2007, 489 patients were included (96% of the target population). Nineteen patients (0.2%) retired their informed consensus or were lost to follow-up immediately after their inclusion. At baseline, mean age of the 470 remaining patients was 40years, mean duration of symptoms was 6.1years; 42% of them were HLA-B27+ and 63% were female. Primary inclusion criterion was IBP in 53%, IA in 27%, ED in 9%, B27+U in 8% and Fam in 4%. Follow-up is still ongoing. CONCLUSION: We have set up a unique diagnostic cohort which includes the entire spectrum of SpA manifestations. By using PDUS we expected to improve the diagnostic procedure of SpA.

Published
2012
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11. Reproducibility of joint swelling assessment by sonography in patients with long-lasting rheumatoid arthritis (SEA-Repro study part II)

Author

Christophe Hudry, Jérémie Sellam, Maxime Dougados, M.A. D'Agostino, F. Etchepare, Cécile Hacquard, Isabelle Chary Valckenaere, Gérard Chalès, Jean David Albert, Sandrine Jousse-Joulin, Laurent Grange, Alain Saraux, Thierry Marhadour, Jacques Bentin, Damien Loeuille, Philippe Gaudin, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Service de Rhumatologie, CHU Brugmann, CHU Brugmann, Belgium, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Physiopathologie, Pharmacologie et Ingénierie articulaires (PPIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Service de rhumatologie, Hôpital Sud, Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Physiopathologie, Pharmacologie et Ingénierie articulaires ( PPIA ), Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]

Subjects
Male, Settore MED/16 - REUMATOLOGIA, MESH: Synovitis, MESH : Aged, Severity of Illness Index, Arthritis, Rheumatoid, 0302 clinical medicine, Cohen's kappa, Rheumatoid, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, 030212 general & internal medicine, Disease activity, MESH : Joints, Ultrasonography, MESH : Synovitis, MESH: Aged, MESH: Arthritis, Rheumatoid, Synovitis, MESH: Middle Aged, medicine.diagnostic_test, Doppler, Middle Aged, Reference Standards, MESH : Ultrasonography, Doppler, MESH: Reproducibility of Results, MESH: Joints, Rheumatoid arthritis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Severity of Illness Index, Female, MESH: Reference Standards, Long lasting, medicine.medical_specialty, MESH : Male, Immunology, Physical examination, 03 medical and health sciences, Rheumatology, MESH: Severity of Illness Index, Ultrasound, medicine, Humans, In patient, MESH : Middle Aged, Aged, 030203 arthritis & rheumatology, Reproducibility, MESH: Humans, business.industry, MESH : Reproducibility of Results, Arthritis, MESH : Humans, Reproducibility of Results, Ultrasonography, Doppler, medicine.disease, MESH: Male, Surgery, Sonographer, MESH : Arthritis, Rheumatoid, MESH : Reference Standards, MESH: Ultrasonography, Doppler, Joints, Nuclear medicine, business, MESH: Female
Abstract

Objective.To evaluate the intraobserver and interobserver reproducibility of B-mode and power Doppler (PD) sonography in patients with active long-standing rheumatoid arthritis (RA) comparatively with clinical data.Methods.In each of 7 patients being considered for a change in their RA treatment regimen, 7 healthcare professionals examined the 28 joints used in the Disease Activity Score 28-joint count (DAS28). Then 7 sonographers examined each of the 7 patients twice, using previously published B-mode and PD grading systems. The clinical reference standard was presence of synovitis according to at least 4/7 examiners. The sonographic reference standard was at least grade 1 (ALG1) or 2 (ALG2) synovitis according to at least 4/7 sonographers. Interobserver reproducibility of sonography was assessed versus the sonographer having the best intraobserver reproducibility. Agreement was measured by Cohen’s kappa statistic.Results.Intraobserver and interobserver reproducibility of B-mode and PD used separately was fair to good. Agreement between clinicians and sonographers at all sites using B-mode, PD, and both was 0.46, 0.37, and 0.36, respectively, for grade 1 synovitis; and 0.58, 0.19, and 0.19 for grade 2 synovitis. The number of joints with synovitis was smaller by physical examination (36.7%) than by B-mode with ALG1 (58.6%; p < 0.001). The number of joints with synovitis was higher by physical examination than by PD with both ALG1 (17.8%; p < 0.0001) and ALG2 (6.6%; p < 0.0001).Conclusion.PD findings explain most of the difference between clinical and sonographic joint assessments for synovitis in patients with long-standing RA.

Published
2010
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12. Reproducibility of joint swelling assessments in long-lasting rheumatoid arthritis: Influence on disease activity score-28 values (SEA-repro study part I)

Author

Laurent Grange, Jean-David Albert, Christophe Hudry, Jérémie Sellam, F. Etchepare, Cécile Hacquard, Sandrine Jousse-Joulin, M.A. D'Agostino, Maxime Dougados, Thierry Marhadour, Alain Saraux, Philippe Gaudin, Gérard Chalès, Isabelle Chary Valckenaere, Jacques Bentin, Damien Loeuille, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Physiopathologie, Pharmacologie et Ingénierie articulaires (PPIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie, CHU Brugmann, CHU Brugmann, Belgium, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, Hôpital Sud, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Physiopathologie, Pharmacologie et Ingénierie articulaires ( PPIA ), Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), and Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, Settore MED/16 - REUMATOLOGIA, MESH: Synovitis, MESH : Aged, Arthritis, Severity of Illness Index, Arthritis, Rheumatoid, 0302 clinical medicine, Cohen's kappa, Rheumatoid, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, MESH : Female, MESH : Joints, Ultrasonography, MESH : Synovitis, MESH: Aged, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, Synovitis, Disease activity score-28, Technician, Middle Aged, Reference Standards, Reproducibility, MESH: Reproducibility of Results, MESH: Joints, Rheumatoid arthritis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Severity of Illness Index, MESH: Reference Standards, Female, musculoskeletal diseases, medicine.medical_specialty, MESH : Male, Immunology, Rheumatoid Arthritis, Disease activity, 03 medical and health sciences, Rheumatology, MESH: Severity of Illness Index, Severity of illness, medicine, Humans, MESH : Middle Aged, Joint swelling, Aged, 030203 arthritis & rheumatology, MESH: Humans, business.industry, MESH : Reproducibility of Results, MESH : Humans, Reproducibility of Results, medicine.disease, MESH: Male, MESH : Reference Standards, MESH : Arthritis, Rheumatoid, Physical therapy, Joints, business, MESH: Female, 030215 immunology
Abstract

Objectives.To evaluate the reproducibility of clinical synovitis assessments in rheumatoid arthritis and the effect of variability on the Disease Activity Score-28 (DAS28).Methods.Seven healthcare professionals from different cities examined the same patients with active non-early rheumatoid arthritis (RA; duration > 4 yrs), for whom a treatment change was being considered. There was no training session and the examination was to be performed as quickly as possible. The healthcare professionals assessed the 28 joints of the DAS28 in 7 patients (196 joints), then reexamined the same 28 joints in 4 of these 7 patients (112 joints), who had been rendered unrecognizable. Then 7 sonographers examined each of the 7 patients twice, using B-mode and power Doppler ultrasound (PD). The reference standards were presence of synovitis according to at least 50% of clinical examiners and 50% of sonographers. Agreement was assessed by Cohen’s kappa statistic.Results.Intraobserver reliability ranged from 0.31 (least experienced research technician) to 0.77 (most experienced physician). Interobserver reliability ranged from 0.18 to 0.62. The largest difference between the lowest and the highest swollen joint counts in the same patient was 15, and the greatest variation in the DAS28 score was 0.92. Agreement between clinical and sonographic reference standards was 0.46, 0.37, and 0.36 for B-mode, PD, and both, respectively.Conclusion.Clinical inter- and intraobserver reliability is highly dependent on the examiner. Consequences on the DAS28 score can be substantial. Agreement with sonography is poor when both B-mode and PD are used but seems better, although low, when B-mode is used alone.

Published
2010
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13. Alteration of antigen-independent immunologic synapse formation between dendritic cells from HLA-B27-transgenic rats and CD4+ T cells: selective impairment of costimulatory molecule engagement by mature HLA-B27

Author

Maxime Breban, Ingrid Fert, Maria-Sole Chimenti, Claudine André, Benoît Giquel, Emmanuel Donnadieu, Cécile Hacquard-Bouder, and Alain Schmitt

Subjects
musculoskeletal diseases, CD4-Positive T-Lymphocytes, Male, Lymphocyte, Immunology, Genetically Modified, Cell Communication, Biology, Animals, Genetically Modified, Interleukin 21, Rheumatology, Antigen, Cell Movement, medicine, Immunology and Allergy, Cytotoxic T cell, Animals, Pharmacology (medical), Antigens, HLA-B27 Antigen, CD27, CD86, Inbred F344, Animal, CD28, T lymphocyte, Dendritic cell, Dendritic Cells, Rats, Inbred F344, Tumor Necrosis Factor Receptor Superfamily, Member 7, Cell biology, Rats, Disease Models, Animal, Settore MED/16 - Reumatologia, medicine.anatomical_structure, Synapses, Antigens, CD27, Female, Spondylarthropathies, Disease Models
Abstract

Objective To investigate the molecular mechanism responsible for the reduced capacity of dendritic cells (DCs) from HLA–B27–transgenic rats to form conjugates with naive T cells. Methods We monitored interactions between DCs derived from HLA–B27–transgenic, HLA–B7–transgenic control, and nontransgenic rats and naive CD4+ T cells. Chemoattraction was studied in Transwell assays, and the formation of an immunologic synapse was examined by videomicroscopy and electron microscopy. Involvement of specific molecules in the defective interaction was examined in antibody-blocking assays. Results T cells migrated normally toward B27 DCs, but upon contact, the frequency of T cells undergoing a Ca2+ response was decreased, indicating impaired immunologic synapse formation. The immunologic synapse formed between B27 DCs and T cells appeared to be normal, as assessed by electron microscopy and by the Ca2+ response. Blocking lymphocyte function−associated antigen 1 on T cells or blocking activated leukocyte cell adhesion molecules on DCs inhibited an equivalent proportion of conjugates from forming between B27 or control DCs and T cells, whereas blocking CD86 on DCs and blocking CD28, CD2, or CD4 on T cells inhibited a greater number of conjugates from forming with control DCs, indicating specific involvement of costimulatory molecules in the reduced formation of conjugates with B27 DCs. Mature B27 molecules on the DC surface were responsible for this decreased formation of conjugates. Conclusion In the HLA–B27–transgenic rat model of spondylarthropathy, mature B27 molecules expressed by DCs impair the formation of an antigen-independent immunologic synapse with naive CD4+ T cells by interfering with the engagement of costimulatory molecules. This phenomenon could potentially affect the production and/or maintenance of regulatory T cells and contribute to the expansion of pathogenic CD4+ T cells.

Published
2007

14. Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA-B27-transgenic rat model of spondylarthropathy

Author

Géraldine Falgarone, M. Ittah, Maxime Breban, Antoine Bosquet, Faïza Smaoui, Dominique Monnet, and Cécile Hacquard-Bouder

Subjects
Male, Lymphocyte, T cell, T-Lymphocytes, Immunology, Antigen-Presenting Cells, Major histocompatibility complex, Immunophenotyping, Animals, Genetically Modified, HLA-B7 Antigen, Rheumatology, Antigen, Rats, Inbred BN, medicine, Immunology and Allergy, Animals, Pharmacology (medical), Antigen-presenting cell, HLA-B27 Antigen, CD86, CD40, biology, business.industry, T-cell receptor, hemic and immune systems, Dendritic Cells, Flow Cytometry, Rats, Inbred F344, Cell biology, Rats, Disease Models, Animal, medicine.anatomical_structure, Rats, Inbred Lew, Chronic Disease, biology.protein, Spondylarthropathies, Female, business
Abstract

Objective A disease resembling the human spondylarthropathies develops in HLA–B27–transgenic rats. This disease in rats is mediated by CD4+ T cells, but antigen-presenting cells (APCs) may also play a role. Dendritic cells (DCs) have been reported to be defective in allogeneic mixed lymphocyte culture in this model. Here, we further investigated the functional defect of APCs. Methods DCs and B cells from nontransgenic, HLA–B27 (33–3)–transgenic, and HLA–B7 (120–4)–transgenic rats were used to stimulate T cells. Surface expression of HLA–B transgene and rat molecules on APCs and the formation of conjugates between DCs and T cells were monitored by flow cytometry. Results We observed a strikingly defective stimulation of allogeneic and syngeneic T lymphocytes by APCs from HLA–B27 but not HLA–B7 rats, even if stimulation was driven in the presence of anti–T cell receptor (TCR) antibody. We found no evidence that HLA–B27 DCs were immature, lacked production of some diffusible factor, or produced an inhibitory factor for T cells. When comparing the levels of expression of class II major histocompatibility complex, CD2, intercellular adhesion molecule 1, lymphocyte function–associated antigen 1, B7, and CD40 molecules at the surface of DCs from 33-3, 120-4, and nontransgenic rats, we found little difference. However, HLA–B27–transgenic DCs formed fewer conjugates with T cells than did nontransgenic DCs. Furthermore, the proportion of conjugates formed between DCs and T cells, as well as the difference between nontransgenic and HLA–B27–transgenic DCs, were in large part reduced by blocking CD86 on DCs. Conclusion We confirmed defective stimulation of T cells by APCs in HLA–B27 rats, the mechanism of which appears to implicate APC/T cell contact, independent of TCR engagement. In addition, decreased use of the CD86 costimulatory molecule by B27 DCs was observed. Impaired costimulatory function could result in a loss of tolerance toward microbial flora in this model.

Published
2004

15. Assessment of peripheral enthesitis in the spondylarthropathies by ultrasonography combined with power Doppler: A cross-sectional study

Author

Maxime Breban, Cécile Hacquard-Bouder, Maxime Dougados, Maria Antonietta D'Agostino, Roula Said-Nahal, and Jean-Louis Brasseur

Subjects
Adult, Male, medicine.medical_specialty, Pathology, Settore MED/16 - REUMATOLOGIA, Cross-sectional study, Immunology, Severity of Illness Index, Arthritis, Rheumatoid, Tendons, Rheumatology, Rheumatoid, medicine, Prevalence, Immunology and Allergy, Humans, Pharmacology (medical), Spondylarthropathies, Ultrasonography, Ligaments, business.industry, Arthritis, Enthesitis, Doppler, Ultrasonography, Doppler, Middle Aged, Enthesis, medicine.disease, Tendon, Peripheral, medicine.anatomical_structure, Cross-Sectional Studies, Rheumatoid arthritis, Tendinopathy, Cortical bone, Female, Radiology, medicine.symptom, business, Low Back Pain, Joint Capsule
Abstract

Objective To assess the prevalence and severity of peripheral enthesitis among the different subtypes of spondylarthropathy (SpA) by using ultrasonography (US) in B mode with power Doppler. Methods One hundred sixty-four consecutive patients with SpA (according to the criteria of the European Spondylarthropathy Study Group) and 64 control patients (34 with mechanical low back pain [MBP] and 30 with rheumatoid arthritis [RA]) underwent US examination of major entheses of their limbs. Particular attention was given to the detection of vascularization at the following sites: cortical bone insertion of entheses, junction between tendon and entheses, body of tendon, and bursa. Results Abnormal US findings consistent with at least one enthesitis were observed in 161 of 164 SpA patients (98%), affecting 1,131 of 2,952 entheses examined (38%). In contrast, only 132 of 1,152 entheses (11%) were found to be abnormal in 33 of 64 control patients (52%). US enthesitis was most commonly distributed in the distal portion of the lower limbs, irrespective of SpA subtype and of skeletal distribution of clinical symptoms. None of the abnormal entheses in control patients showed vascularization, compared with 916 of 1,131 abnormal entheses in SpA patients (81%), where it was always detected at the cortical bone insertion and sometimes also in the bursa. In SpA patients, the US pattern depended on the clinical presentation, with a higher prevalence of the most severe stages in those with peripheral forms. Conclusion US in B mode combined with power Doppler allowed the detection of peripheral enthesitis in a majority of SpA patients, but not in MBP or RA patients. The presence of entheseal involvement was independent of SpA subtype, but its degree of severity appeared to be greater in peripheral forms. US could be very useful for both the diagnosis and the assessment of SpA activity.

Published
2003

16. Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA–B27–transgenic rat model of spondylarthropathy.

Author

Cécile Hacquard-Bouder, Géraldine Falgarone, Antoine Bosquet, Faïza Smaoui, Dominique Monnet, Marc Ittah, and Maxime Breban

Subjects
*CELLULAR mechanics, *SPONDYLOARTHROPATHIES, *DENDRITIC cells, *ANTIGEN presenting cells, *LYMPHOCYTES, *ANIMAL experimentation, *T cells, *LYMPHOID tissue, *LEUCOCYTES, *B cells, *T cell receptors, *CELL membranes, *CELL receptors, *HLA histocompatibility antigens
Abstract

A disease resembling the human spondylarthropathies develops in HLA–B27–transgenic rats. This disease in rats is mediated by CD4+ T cells, but antigen-presenting cells (APCs) may also play a role. Dendritic cells (DCs) have been reported to be defective in allogeneic mixed lymphocyte culture in this model. Here, we further investigated the functional defect of APCs. DCs and B cells from nontransgenic, HLA–B27 (33–3)–transgenic, and HLA–B7 (120–4)–transgenic rats were used to stimulate T cells. Surface expression of HLA–B transgene and rat molecules on APCs and the formation of conjugates between DCs and T cells were monitored by flow cytometry. We observed a strikingly defective stimulation of allogeneic and syngeneic T lymphocytes by APCs from HLA–B27 but not HLA–B7 rats, even if stimulation was driven in the presence of anti–T cell receptor (TCR) antibody. We found no evidence that HLA–B27 DCs were immature, lacked production of some diffusible factor, or produced an inhibitory factor for T cells. When comparing the levels of expression of class II major histocompatibility complex, CD2, intercellular adhesion molecule 1, lymphocyte function–associated antigen 1, B7, and CD40 molecules at the surface of DCs from 33-3, 120-4, and nontransgenic rats, we found little difference. However, HLA–B27–transgenic DCs formed fewer conjugates with T cells than did nontransgenic DCs. Furthermore, the proportion of conjugates formed between DCs and T cells, as well as the difference between nontransgenic and HLA–B27–transgenic DCs, were in large part reduced by blocking CD86 on DCs. We confirmed defective stimulation of T cells by APCs in HLA–B27 rats, the mechanism of which appears to implicate APC/T cell contact, independent of TCR engagement. In addition, decreased use of the CD86 costimulatory molecule by B27 DCs was observed. Impaired costimulatory function could result in a loss of tolerance toward microbial flora in this model. [ABSTRACT FROM AUTHOR]

Published
2004
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