Allanore lab

Hôpital Cochin
Service de Rhumatologie A, INSERM 1016
27 rue du Faubourg Saint Jacques
75014 Paris, France

Yannick Allanore, MD, PhD

Pr of Rheumatology
yannick.allanore[at]inserm.fr tel: +33 1 5841 2563
fax: +33 1 5841 2624

Systemic sclerosis (SSc) is an orphan disease characterized by vascular, immune and connective tissue anomalies. Among the many different immune-mediated rheumatic diseases, SSc stands out as a severely incapacitating and life-threatening disease, the pathogenesis of which is largely unknown and for which therapeutic options are few and insufficient. SSc is not inherited in a Mendelian fashion and it is believed that both genetic and environmental factors contribute to disease susceptibility and disease progression.

Our group is from a long time committed to decipher the genetics of SSc through several large multinational candidate gene studies and the recent achievement of a genome-wide association study. Major progresses have been recently achieved and several risk loci have been identified, most of them are involved in autoimmunity. This is a major breakthrough in SSc, switching to a new paradigm of the disease which was until recently considered only as a fibroblast dysfunction condition. However, this also raises new questions such as the precise role of these immune genes on SSc phenotype in comparison to other autoimmune diseases to which they are also often associated. Therefore, there is a clear need to proceed now to their functional validation through a translational approaches. To this end, we aim to delineate the role of SSc-associated genes and to unravel the molecular pathways by which they are implicated in tissue fibrosis with the use of relevant and complementary SSc animal models but also animal models of erosive arthritis to evaluate the role of pleiotropic genes.

Concomitantly, we are performing several clinical research projects in particular in the cardiovascular aspects of rheumatic disorders to try to identify relevant outcomes measures, biomarkers and therapeutic strategies.

People

Léa Remy-Tourneur, PhD, Professor

Jérôme Avouac, MD, PhD, Assistant Professor

Julien Wipff, MD, PhD, Assistant Professor

Muriel Elhaï: PhD student, fellow

Agathe Leblond, Master 2 student

Sara Mouasni, Master 2 student

Marie-Agnès Blaton, Assistant Engineer

Sonia Pezet, Assistant Engineer

Anne Cauvet Burgevin: Assistant Engineer

Funding

Arthritis

Functional validation of genetic hypotheses in systemic sclerosis animal models. [2011-2012]

Fondation Société Française de Rhumatologie

Nuclear family recruitment and genetics of systemic sclerosis. [2009-2010]

Association des Sclérodermie de France

Relevance of IRF5 and STAT4 genes in the pathogenesis of systemic sclerosis: input from animal models. [2009]

ANR GENOPATH

Genomewide association study in European Caucasian Systemic Sclerosis patients. ANR-08-GENO-016-1 (Project R08160KS) [2008]

Fondation Arthritis

Endothelial disturbances in systemic sclerosis: a cellular approach based on endothelial cells derived from circulating endothelial progenitors. [2007-2009]

ANR GiS-Maladies Rares

Vasculopathy of systemic sclerosis: molecular and cellular approaches. (MRAR-2007-projet R07094KS) [2007]

Selected Pubications

Basic and translational

The nuclear receptor CAR / NR1I3 enhances the pro-fibrotic effects of TGF-β and contributes to the development of experimental dermal fibrosis.

Avouac J1, Palumbo-Zerr K, Ruzehaji N, Tomcik M, Zerr P, Dees C, Distler A, Beyer C, Schneider H, Distler O, Schett G, Allanore Y, Distler JH.
Arthritis Rheumatol. 2014 Aug 22. doi: 10.1002/art.38819

Targeting IL-6 by both passive or active immunization strategies prevents bleomycin-induced skin fibrosis.

Desallais L, Avouac J, Fréchet M, Elhai M, Ratsimandresy R, Montes M, Mouhsine H, Do H, Zagury JF, Allanore Y.
Arthritis Res Ther. 2014 Jul 24;16(4):R157

Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibility gene.

Gazal S, Sacre K, Allanore Y, Teruel M, Goodall AH; (The CARDIOGENICS consortium), Tohma S, Alfredsson L, Okada Y, Xie G, Constantin A, Balsa A, Kawasaki A, Nicaise P, Amos C, Rodriguez-Rodriguez L, Chioccia G, Boileau C, Zhang J, Vittecoq O, Barnetche T, Gonzalez Gay MA, Furukawa H, Cantagrel A, Le Loët X, Sumida T, Hurtado-Nedelec M, Richez C, Chollet-Martin S, Schaeverbeke T, Combe B, Khoryati L, Coustet B, El-Benna J, Siminovitch K, Plenge R, Padyukov L, Martin J, Tsuchiya N, Dieudé P.
Ann Rheum Dis. 2014 Jan 21. doi: 10.1136

TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients.

Koumakis E, Wipff J, Dieudé P, Ruiz B, Bouaziz M, Revillod L, Guedj M, Distler JH, Matucci-Cerinic M, Humbert M, Riemekasten G, Airo P, Melchers I, Hachulla E, Cusi D, Wichmann HE, Hunzelmann N, Tiev K, Caramaschi P, Diot E, Kowal-Bielecka O, Cuomo G, Walker U, Czirják L, Damjanov N, Lupoli S, Conti C, Müller-Nurasyid M, Müller-Ladner U, Riccieri V, Cracowski JL, Cozzi F, Bournia VK, Vlachoyiannopoulos P, Chiocchia G, Boileau C, Allanore Y.
Ann Rheum Dis. 2012;71(11):1900-3

Candidate gene study in systemic sclerosis identifies a rare and functional variant of the TNFAIP3 locus as a risk factor for polyautoimmunity.

Koumakis E, Giraud M, Dieudé P, Cohignac V, Cuomo G, Airò P, Hachulla E, Matucci-Cerinic M, Diot E, Caramaschi P, Mouthon L, Riccieri V, Cracowski JL, Tiev KP, Francès C, Amoura Z, Sibilia J, Cosnes A, Carpentier P, Valentini G, Manetti M, Guiducci S, Meyer O, Kahan A, Boileau C, Chiocchia G, Allanore Y.
Arthritis Rheum. 2012 64, 2746-52.

Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis.

Manetti M, Allanore Y, Saad M, Fatini C, Cohignac V, Guiducci S, Romano E, Airó P, Caramaschi P, Tinazzi I, Riccieri V, Rossa AD, Abbate R, Caporali R, Cuomo G, Valesini G, Dieudé P, Hachulla E, Cracowski JL, Tiev K, Letenneur L, Amouyel P, Lambert JC, Chiocchia G, Martinez M, Ibba-Manneschi L, Matucci-Cerinic M.
Ann Rheum Dis. 2012;71(6):1034-41

Independent Replication and Metaanalysis of Association Studies Establish TNFSF4 as a Susceptibility Gene Preferentially Associated with the Subset of Anticentromere-positive Patients with Systemic Sclerosis.

Coustet B, Bouaziz M, Dieudé P, Guedj M, Bossini-Castillo L, Agarwal S, Radstake T, Martin J, Gourh P, Elhai M, Koumakis E, Avouac J, Ruiz B, Mayes M, Arnett F, Hachulla E, Diot E, Cracowski JL, Tiev K, Sibilia J, Mouthon L, Frances C, Amoura Z, Carpentier P, Cosnes A, Meyer O, Kahan A, Boileau C, Chiocchia G, Allanore Y.
J Rheumatol. 2012;39(5):997-1003

Evidence of the contribution of the X chromosome to systemic sclerosis susceptibility: association with the functional IRAK1 196Phe/532Ser haplotype.

Dieudé P, Bouaziz M, Guedj M, Riemekasten G, Airò P, Müller M, Cusi D, Matucci-Cerinic M, Melchers I, Koenig W, Salvi E, Wichmann HE, Cuomo G, Hachulla E, Diot E, Hunzelmann N, Caramaschi P, Mouthon L, Riccieri V, Distler J, Tarner I, Avouac J, Meyer O, Kahan A, Chiocchia G, Boileau C, Allanore Y.
Arthritis Rheum. (2011) 63, 3979-87

Genome-Wide Scan identifies TNIP1, PSORS1C1 and RHOB as novel risk loci for Systemic Sclerosis.

Allanore Y, Saad M, Dieude P et al.
Plos Genetics (2011) 7, e1002091

Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis.

Avouac J, Meune C, Ruiz B, Couraud PO, Uzan G, Boileau C, Kahan A, Chiocchia G, Allanore Y.
Ann Rheum Dis. 2012;71(3):394-9

C8orf13-BLK is a genetic risk locus for systemic sclerosis and has additive effects with BANK1: results from a large french cohort and meta-analysis.

Coustet B, Dieudé P, Guedj M, Bouaziz M, Avouac J, Ruiz B, Hachulla E, Diot E, Cracowski JL, Tiev K, Sibilia J, Mouthon L, Frances C, Amoura Z, Carpentier P, Cosnes A, Meyer O, Kahan A, Boileau C, Chiocchia G, Allanore Y.
Arthritis Rheum. (2011) 63, 2091-6.

Inactivation of the transcription factor STAT-4 prevents inflammation-driven fibrosis in animal models of systemic sclerosis.

Fürnrohr BG, Tomcik M, Palumbo K, Zerr P, Horn A, Dees C, Akhmetshina A, Beyer C, Distler O, Schett G, Allanore Y, Distler JH.
Arthritis Rheum. (2011) 63, 800-9.

A regulatory variant in CCR6 is associated with anti-topoisomerase positive systemic sclerosis susceptibility

• Koumakis E, Bouaziz M, Dieudé P, Ruiz B, Riemekasten G, Airo P, Müller-Nurasyid M, Cusi D, Matucci-Cerinic M, Melchers I, Salvi E, Strauch K, Peters A, Cuomo G, Hachulla E, Diot E, Hunzelmann N, Caramaschi P, Riccieri V, Distler JH, Tarner I, Avouac J, Letenneur L, Amouyel P, Lambert JC, Chiocchia G, Boileau C, Allanore Y
Arthritis Rheum. 2013 Aug 27. doi: 10.1002/art.38136

The MUC5B variant is associated with idiopathic pulmonary fibrosis but not with systemic sclerosis interstitial lung disease in the European Caucasian population

• Borie R, Crestani B, Dieude P, Nunes H, Allanore Y, Kannengiesser C, Airo P, Matucci-Cerinic M, Wallaert B, Israel-Biet D, Cadranel J, Cottin V, Gazal S, Peljto AL, Varga J, Schwartz DA, Valeyre D, Grandchamp B
PLoS One. 2013 Aug 5;8(8):e70621

Systemic sclerosis at the crossroad of polyautoimmunity

• Elhai M, Avouac J, Kahan A, Allanore Y
Autoimmun Rev. 2013 Sep;12(11):1052-7

Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis

Génin E, Coustet B, Allanore Y, Ito I, Teruel M, Constantin A, Schaeverbeke T, Ruyssen-Witrand A, Tohma S, Cantagrel A, Vittecoq O, Barnetche T, Le Loët X, Fardellone P, Furukawa H, Meyer O, Fernández-Gutiérrez B, Balsa A, González-Gay MA, Chiocchia G, Tsuchiya N, Martin J, Dieudé P
PLoS One. 2013 Apr 30;8(4):e61044

Correlations between angiogenic factors and capillaroscopic patterns in systemic sclerosis

• Avouac J, Vallucci M, Smith V, Senet P, Ruiz B, Sulli A, Pizzorni C, Frances C, Chiocchia G, Cutolo M, Allanore Y
Arthritis Res Ther. 2013 Apr 19;15(2):R55

Performance of skin ultrasound to measure skin involvement in different animal models of systemic sclerosis

Elhai M, Jérôme Avouac, Marchiol C, Renault G, Ruiz B, Fréchet M, Chiocchia G, Allanore Y
Ultrasound Med Biol. 2013 May;39(5):845-52

Critical role of the adhesion receptor DNAX accessory molecule-1 (DNAM-1) in the development of inflammation-driven dermal fibrosis in a mouse model of systemic sclerosis

• Avouac J, Elhai M, Tomcik M, Ruiz B, Friese M, Piedavent M, Colonna M, Bernhardt G, Kahan A, Chiocchia G, Distler JH, Allanore Y
Ann Rheum Dis. 2013 Jun;72(6):1089-98

Clinical Research

A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study.

Elhai M, Avouac J, Walker UA, Matucci-Cerinic M, Riemekasten G, Airò P, Hachulla E, Valentini G, Carreira PE, Cozzi F, Balbir Gurman A, Braun-Moscovici Y, Damjanov N, Ananieva LP, Scorza R, Jimenez S, Busquets J, Li M, Müller-Ladner U, Kahan A, Distler O, Allanore Y; EUSTAR co-authors.
Ann Rheum Dis. 2014 Oct 23. pii: annrheumdis-2014-206386. doi: 10.1136

Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study.

Avouac J, Walker UA, Hachulla E, Riemekasten G, Cuomo G, Carreira PE, Caramaschi P, Ananieva LP, Matucci-Cerinic M, Czirjak L, Denton C, Ladner UM, Allanore Y; the EUSTAR collaborators.
Ann Rheum Dis. 2014 Aug 27. pii: annrheumdis-2014-205295. doi: 10.1136

International consensus criteria for the diagnosis of Raynaud's phenomenon.

Maverakis E, Patel F, Kronenberg DG, Chung L, Fiorentino D, Allanore Y, Guiducci S, Hesselstrand R, Hummers LK, Duong C, Kahaleh B, Macgregor A, Matucci-Cerinic M, Wollheim FA, Mayes MD, Gershwin ME.
J Autoimmun. 2014 Feb-Mar;48-49:60-5

Familial Autoimmunity in Systemic Sclerosis - Results of a French-based Case-control Family Study.

Koumakis E, Dieudé P, Avouac J, Kahan A, Allanore Y.
J Rheumatol. 2012 Jan 15. [Epub ahead of print]

Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies

Elhai M, Meune C, Avouac J, Kahan A, Allanore Y
Rheumatology (Oxford). 2012;51(6):1017-26

Prediction of pulmonary hypertension related to systemic sclerosis by an index based on simple clinical observations

Meune C, Avouac J, Airò P, Beretta L, Dieudé P, Wahbi K, Caramaschi P, Tiev K, Cappelli S, Diot E, Vacca A, Cracowski JL, Sibilia J, Kahan A, Matucci-Cerinic M, Allanore Y
Arthritis Rheum. 2011;63(9):2790-6

Hand and Wrist Involvement in Systemic Sclerosis: US Features

Freire V, Bazeli R, Elhai M, Campagna R, Pessis E, Avouac J, Allanore Y, Drapé JL, Guérini H
Radiology. 2013 Dec;269(3):824-30

Combination of echocardiographic and pulmonary function test measures improves sensitivity for diagnosis of systemic sclerosis-associated pulmonary arterial hypertension: analysis of 2 cohorts

Gladue H, Steen V, Allanore Y, Saggar R, Saggar R, Maranian P, Berrocal VJ, Avouac J, Meune C, Trivedi M, Khanna D
J Rheumatol. 2013 Oct;40(10):1706-11

Associations between a scleroderma-specific gastrointestinal instrument and objective tests of upper gastrointestinal involvements in systemic sclerosis

Bae S, Allanore Y, Furst DE, Bodukam V, Coustet B, Morgaceva O, Maranian P, Khanna D
Clin Exp Rheumatol. 2013 Mar-Apr;31(2 Suppl 76):57-63

Comparison of pain, pain burden, coping strategies, and attitudes between patients with systemic sclerosis and patients with rheumatoid arthritis: a cross-sectional study

Perrot S, Dieudé P, Pérocheau D, Allanore Y
Pain Med. 2013 Nov;14(11):1776-85

Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials

Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL
Ann Rheum Dis. 2013 Oct;72(10):1696-9

Expert consensus for performing right heart catheterisation for suspected pulmonary arterial hypertension in systemic sclerosis: a Delphi consensus study with cluster analysis

Avouac J, Huscher D, Furst DE, Opitz CF, Distler O, Allanore Y; for the EPOSS group
Ann Rheum Dis. 2013 Feb 20

Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study

Elhai M, Meunier M, Matucci-Cerinic M, Maurer B, Riemekasten G, Leturcq T, Pellerito R, Von Mühlen CA, Vacca A, Airo P, Bartoli F, Fiori G, Bokarewa M, Riccieri V, Becker M, Avouac J, Müller-Ladner U, Distler O, Allanore Y; EUSTAR (EULAR Scleroderma Trials and Research group)
Ann Rheum Dis. 2013 Jul;72(7):1217-20

Increased risk of osteoporosis and fracture in women with systemic sclerosis: a comparative study with rheumatoid arthritis

Avouac J, Koumakis E, Toth E, Meunier M, Maury E, Kahan A, Cormier C, Allanore Y
Arthritis Care Res (Hoboken). 2012 Dec;64(12):1871-8

Articular involvement in systemic sclerosis

Avouac J, Clements PJ, Khanna D, Furst DE, Allanore Y
Rheumatology (Oxford). 2012 Aug;51(8):1347-56

Ultrasonographic hand features in systemic sclerosis and correlates with clinical, biologic, and radiographic findings

Elhai M, Guerini H, Bazeli R, Avouac J, Freire V, Drapé JL, Kahan A, Allanore Y
Arthritis Care Res (Hoboken). 2012 Aug;64(8):1244-9