Sjogren Big Data Project: Influence of Geolocation on the Phenotypic Expression at Diagnosis in 8310 Patients (North-to-South Gradient)

Pilar Brito-Zerón^1,2, Soledad Retamozo³, Margit Zeher⁴, Astrid Rasmussen⁵, Raphaele Seror⁶, Elke Theander⁷, Xiaomei Li⁸, Chiara Baldini⁹, Jacques-Eric Gottenberg¹⁰, Debashish Danda¹¹, Luca Quartuccio¹², Roberta Priori^13,14, Gabriela Hernandez-Molina¹⁵, Aike A. Kruize¹⁶, Valeria Valim¹⁷, Marika Kvarnström¹⁸, Damien Sene¹⁹, Roberto Gerli²⁰, Sonja Praprotnik²¹, David A. Isenberg²², Roser Solans²³, Maureen Rischmueller²⁴, Seung-Ki Kwok²⁵, Gunnel Nordmark²⁶, Yasunori Suzuki²⁷, Roberto Giacomelli²⁸, Valerie Devauchelle²⁹, Michele Bombardieri³⁰, Benedikt Hofauer³¹, Hendrika Bootsma³², Johan G. Brun³³, Guadalupe Fraile³⁴, Steven E. Carsons³⁵, Tamer Gheita³⁶, Jacques Morel³⁷, Cristina F. Vollenweider³⁸, Fabiola Atzeni³⁹, Nihan Acar-Denizli⁴⁰, Ildike-Fanny Horvath⁴, Kathy Sivils⁵, Thomas Mandl⁴¹, Pulukool Sandhya¹¹, Salvatore De Vita⁴², Jorge Sánchez-Guerrero⁴³, Eefje van der Heijden¹⁶, Virginia Moça Trevisano⁴⁴, Marie Wahren-Herlenius¹⁸, Xavier Mariette⁶, Manuel Ramos-Casals^1,45,46 and EULAR-SS Task Force Big Data Consortium (ASSES, GEAS-SEMI, EULAR), ¹Laboratory of Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Spain, Barcelona, Spain, ²Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona., Bacelona, Spain, ³Rheumatology Unit, Hospital Privado Centro Médico de Córdoba, Argentina, Córdoba, Argentina, ⁴Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Debrecen, Hungary, ⁵Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, USA, Oklahoma City, OK, ⁶Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France, Paris, France, ⁷Department of Rheumatology, Malmö University Hospital, Lund University, Sweden, Malmö, Sweden, ⁸Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital, China, Hefei, Anhui, China, ⁹Rheumatology Unit, University of Pisa, Italy, Pisa, Italy, ¹⁰Department of Rheumatology, Strasbourg University Hospital, Université de Strasbourg, CNRS, Strasbourg, France, Strasbourg, France, ¹¹Clinical Immunology & Rheumatology, Christian Medical College, Vellore, India, Vellore, India, ¹²Rheumatology Clinic, DSMB, University of Udine, Udine, Italy, Udine, Italy, ¹³Rheumatology Unit, Sapienza University of Rome, Rome, Italy, ¹⁴Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy, ¹⁵Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico City, Mexico, ¹⁶Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands, Utrecht, Netherlands, ¹⁷Rheumatology, Department of Medicine, Universidade Federal do Espírito Santo, Vitória, Brazil, Vitória, Brazil, ¹⁸Department of Medicine, Solna, Unit of Experimental Rheumatology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ¹⁹Service de Médecine Interne 2, Hôpital Lariboisière, Université Paris VII, Assistance Publique-Hôpitaux de Paris, 2, Paris, France, Paris, France, ²⁰Clinical and Experimental Medicine, Rheumatology Unit, University of Perugia, Italy, Perugia, Italy, ²¹Department of Rheumatology, University Medical Centre Ljubljana, Slovenia, Ljubljana, Slovenia, ²²Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom, ²³Autoimmune Systemic Diseases Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Autonomous University of Barcelona, Spain, Barcelona, Spain, ²⁴Department of Rheumatology, School of Medicine, The University of Western Australia, Crawley, Australia, Crawley, Australia, ²⁵Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul, South Korea, ²⁶Rheumatology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden, Uppsala, Sweden, ²⁷Division of Rheumatology, Kanazawa University Graduate School of Medicine, Ishikawa, Japan, Kanazawa, Japan, ²⁸Clinical Unit of Rheumatology, University of l'Aquila, School of Medicine, L'Aquila, Italy, L'Aquila, Italy, ²⁹Service de Rhumatologie, Department of Rheumatology, Brest University Hospital, Brest, France, Brest, France, ³⁰Willian Harvey Research Institute, Centre for Experimental Medicine and Rheumatology, QMUL, UK, London, United Kingdom, ³¹Hals-Nasen-Ohrenklinik und Poliklinik, Technische Universität München, München, Germany, München, Germany, ³²Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, The Netherlands, Groningen, Netherlands, ³³Department of Clinical Science, University of Bergen. Department of Rheumatology, Haukeland University Hospital, Bergen, Norway, Bergen, Norway, ³⁴Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain, Madrid, Spain, ³⁵Division of Rheumatology, Allergy and Immunology Winthrop-University Hospital, Stony Brook University School of Medicine, NY, USA, Mineola, NY, ³⁶Rheumatology, Rheumatology Department, Faculty of Medicine, Cairo University, Egypt, Cairo, Egypt, ³⁷Department of Rheumatology, Teaching hospital and University of Montpellier, France, Montpellier, France, ³⁸Rheumatology, German Hospital, Buenos Aires, Argentina, Buenos Aires, Argentina, ³⁹IRCCS Galeazzi Orthopedic Institute, Milan, Italy, Milan, Italy, ⁴⁰Department of Statistics, Faculty of Science and Letters, Mimar Sinan Fine Arts University, Turkey, Istabul, Turkey, ⁴¹Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, Rheumatology, Malmö, Sweden, Malmö, Sweden, ⁴²Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy, Udine, Italy, ⁴³Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, Mexico, ⁴⁴Federal University of São Paulo, Sao Paulo, Brazil, San Paulo, Brazil, ⁴⁵Sjögren Syndrome Research Group (AGAUR), Barcelona, Spain, ⁴⁶Department of Medicine, University of Barcelona, Barcelona, Spain., Barcelona, Spain

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Big data, epigenetics and phenotypes, Sjogren's syndrome

Session Information

Date: Sunday, November 13, 2016

Title: Sjögren's Syndrome - Poster I: Translational Science

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: To analyse the influence of geolocation (North-to-South gradient) on the clinical presentation of primary Sjögren syndrome (SjS) at diagnosis.

Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Patients were classified according to the geolocation of the country of the diagnosing hospital. Patients were first classified by continent, with an additional north-south sub-classification according to latitude in continents including patients from > 1 country (latitude > or < 50’N in Europe, equator > or < in America and latitude > or < 30’N in Asia).

Results: We included 7748 (93%) women and 562 (7%) men, with a mean age at diagnosis of primary SjS of 53 years. Multivariate analysis adjusted by age and gender showed that northern European patients (latitude > 50´N) had a lower frequency of ocular dryness (OR=0.39, 95%CI 0.29-0.53), abnormal ocular tests (OR=0.51, 95%CI 0.40-0.65), ANA (OR=0.59, 95%CI 0.47-0.73) and Ro/La autoantibodies (OR=0.71, 95%CI 0.58-0.88) and a higher frequency of abnormal oral tests (OR=1.62, 95%CI 1.26-2.11) and RF (OR=1.86, 95%CI 1.55-2.23) compared with southern European patients. North American patients had a lower frequency of abnormal oral tests (OR=0.55, 95%CI 0.35-0.84) and positive salivary biopsy (OR=0.43, 95%CI 0.18-0.91), and a higher frequency of ANA (OR=1.56, 95%CI 1.03-2.35), Ro/La autoantibodies (OR=2.92, 95%CI 1.95-4.41) and low C4 levels (OR=6.02, 95%CI 1.78-37.63) compared with South American patients. Northern Asian patients had a lower frequency of dry mouth (OR=0.47, 95%CI 0.26-0.83), dry eyes (OR=0.35, 95%CI 0.20-0.59), abnormal ocular tests (OR=0.34, 95%CI 0.19-0.60) and positive salivary biopsy (OR=0.43, 95%CI 0.25-0.74), and a higher frequency of ANA (OR=2.95, 95%CI 1.78-4.97) compared with southern Asian patients.

Conclusion: These results suggest, for the first time, that geolocation may influence the phenotypic expression of primary SjS at diagnosis, including significant geoepidemiological variations in the prevalence of dryness, the frequency of abnormal diagnostic tests and the positivity of the main immunological markers. Geoepidemiology and ethnicity should be considered as key variables that should be analysed in multi-ethnic studies of patients with primary SjS.

Disclosure: P. Brito-Zerón, None; S. Retamozo, None; M. Zeher, None; A. Rasmussen, None; R. Seror, None; E. Theander, None; X. Li, None; C. Baldini, None; J. E. Gottenberg, None; D. Danda, None; L. Quartuccio, None; R. Priori, None; G. Hernandez-Molina, None; A. A. Kruize, None; V. Valim, None; M. Kvarnström, None; D. Sene, None; R. Gerli, None; S. Praprotnik, None; D. A. Isenberg, None; R. Solans, None; M. Rischmueller, None; S. K. Kwok, None; G. Nordmark, None; Y. Suzuki, None; R. Giacomelli, None; V. Devauchelle, None; M. Bombardieri, None; B. Hofauer, None; H. Bootsma, None; J. G. Brun, None; G. Fraile, None; S. E. Carsons, None; T. Gheita, None; J. Morel, None; C. F. Vollenweider, None; F. Atzeni, None; N. Acar-Denizli, None; I. F. Horvath, None; K. Sivils, None; T. Mandl, None; P. Sandhya, None; S. De Vita, None; J. Sánchez-Guerrero, None; E. van der Heijden, None; V. Moça Trevisano, None; M. Wahren-Herlenius, None; X. Mariette, Pfizer, GlaxoSmithKline, and Roche, 2,Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, UCB Pharma and Sanofi-Aventis, 5; M. Ramos-Casals, None.

To cite this abstract in AMA style:

Brito-Zerón P, Retamozo S, Zeher M, Rasmussen A, Seror R, Theander E, Li X, Baldini C, Gottenberg JE, Danda D, Quartuccio L, Priori R, Hernandez-Molina G, Kruize AA, Valim V, Kvarnström M, Sene D, Gerli R, Praprotnik S, Isenberg DA, Solans R, Rischmueller M, Kwok SK, Nordmark G, Suzuki Y, Giacomelli R, Devauchelle V, Bombardieri M, Hofauer B, Bootsma H, Brun JG, Fraile G, Carsons SE, Gheita T, Morel J, Vollenweider CF, Atzeni F, Acar-Denizli N, Horvath IF, Sivils K, Mandl T, Sandhya P, De Vita S, Sánchez-Guerrero J, van der Heijden E, Moça Trevisano V, Wahren-Herlenius M, Mariette X, Ramos-Casals M. Sjogren Big Data Project: Influence of Geolocation on the Phenotypic Expression at Diagnosis in 8310 Patients (North-to-South Gradient) [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/sjogren-big-data-project-influence-of-geolocation-on-the-phenotypic-expression-at-diagnosis-in-8310-patients-north-to-south-gradient/. Accessed .

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