How Does Primary Sjogren Syndrome Present in Biopsy-Proven Patients without Circulating Ro/La Autoantibodies? Characteristics at Diagnosis of 2073 Patients from the SjöGren Big Data Project

Pilar Brito-Zerón^1,2,3, Nihan Acar-Denizli⁴, Margit Zeher⁵, Astrid Rasmussen⁶, Raphaele Seror⁷, Elke Theander⁸, Xiaomei Li⁹, Chiara Baldini¹⁰, Jacques-Eric Gottenberg¹¹, Debashish Danda¹², Luca Quartuccio¹³, Roberta Priori^14,15, Gabriela Hernandez-Molina¹⁶, Aike A. Kruize¹⁷, Valeria Valim¹⁸, Marika Kvarnström¹⁹, Damien Sene²⁰, Roberto Gerli²¹, Sonja Praprotnik²², David A. Isenberg²³, Roser Solans²⁴, Maureen Rischmueller²⁵, Seung-Ki Kwok²⁶, Gunnel Nordmark²⁷, Yasunori Suzuki²⁸, Roberto Giacomelli²⁹, Valerie Devauchelle-Pensec³⁰, Michele Bombardieri³¹, Benedikt Hofauer³², Hendrika Bootsma³³, Johan G. Brun³⁴, Guadalupe Fraile³⁵, Steven E. Carsons³⁶, Tamer Gheita³⁷, Jacques Morel³⁸, Cristina F. Vollenweider³⁹, Fabiola Atzeni⁴⁰, Soledad Retamozo⁴¹, Ildike-Fanny Horvath⁵, Kathy Sivils⁶, Thomas Mandl^42,43, Pulukool Sandhya¹², Salvatore De Vita⁴⁴, Jorge Sánchez-Guerrero⁴⁵, Eefje van der Heijden¹⁷, Virginia Moça Trevisano⁴⁶, Marie Wahren-Herlenius¹⁹, Xavier Mariette⁷, Manuel Ramos-Casals^3,47,48 and EULAR-SS Task Force Big Data Consortium (ASSES, GEAS-SEMI, EULAR), ¹Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona., Bacelona, Spain, ²Laboratory 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, Barcelona, Spain, ³Laboratory 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, ⁴Department of Statistics, Faculty of Science and Letters, Mimar Sinan Fine Arts University, Turkey, Istabul, Turkey, ⁵Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Debrecen, Hungary, ⁶Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, USA, Oklahoma City, OK, ⁷Center 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, ⁸Department of Rheumatology, Malmö University Hospital, Lund University, Sweden, Malmö, Sweden, ⁹Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital, China, Hefei, Anhui, China, ¹⁰Rheumatology Unit, University of Pisa, Italy, Pisa, Italy, ¹¹Department of Rheumatology, Strasbourg University Hospital, Université de Strasbourg, CNRS, Strasbourg, France, Strasbourg, France, ¹²Clinical Immunology & Rheumatology, Christian Medical College, Vellore, India, Vellore, India, ¹³Rheumatology Clinic, DSMB, University of Udine, Udine, Italy, Udine, Italy, ¹⁴Rheumatology Unit, Sapienza University of Rome, Rome, Italy, ¹⁵Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy, ¹⁶Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico City, Mexico, ¹⁷Department of Rheumatology & Clinical Immunology, Medical Center Utrecht, The Netherlands, Utrecht, Netherlands, ¹⁸Rheumatology, Department of Medicine, Universidade Federal do Espírito Santo, Vitória, Brazil, Vitória, Brazil, ¹⁹Department of Medicine, Solna, Unit of Experimental Rheumatology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ²⁰Service de Médecine Interne 2, Hôpital Lariboisière, Université Paris VII, Assistance Publique-Hôpitaux de Paris, 2, Paris, France, Paris, France, ²¹Clinical and Experimental Medicine, Rheumatology Unit, University of Perugia, Italy, Perugia, Italy, ²²Department of Rheumatology, University Medical Centre Ljubljana, Slovenia, Ljubljana, Slovenia, ²³Centre for Rheumatology Research, University College Hospital London, UK, London, United Kingdom, ²⁴Autoimmune Systemic Diseases Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Autonomous University of Barcelona, Spain, Barcelona, Spain, ²⁵Department of Rheumatology, School of Medicine, The University of Western Australia, Crawley, Australia, Crawley, Australia, ²⁶[email protected], Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea, ²⁷Rheumatology, Department of Medical Sciences, Uppsala University, Sweden, Uppsala, Sweden, ²⁸Division of Rheumatology , Kanazawa University Hospital , Kanazawa , Ishikawa , Japan, Ishikawa, Japan, ²⁹Clinical Unit of Rheumatology, University of l'Aquila, School of Medicine, L'Aquila, Italy, L'Aquila, Italy, ³⁰Department of Rheumatology, Brest University Hospital, Brest, France, Brest, France, ³¹Willian Harvey Research Institute, Centre for Experimental Medicine and Rheumatology, QMUL, UK, London, United Kingdom, ³²Hals-Nasen-Ohrenklinik und Poliklinik, Technische Universität München, München, Germany, München, Germany, ³³Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, The Netherlands, Groningen, Netherlands, ³⁴Department of Clinical Science, University of Bergen. Department of Rheumatology, Haukeland University Hospital, Bergen, Norway, Bergen, Norway, ³⁵Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain, Madrid, Spain, ³⁶Division of Rheumatology, Allergy and Immunology Winthrop-University Hospital, Stony Brook University School of Medicine, NY, USA, Mineola, NY, ³⁷Rheumatology, Rheumatology Department, Faculty of Medicine, Cairo University, Egypt, Cairo, Egypt, ³⁸Department of Rheumatology, Teaching hospital and University of Montpellier, France, Montpellier, France, ³⁹Rheumatology, German Hospital, Buenos Aires, Argentina, Buenos Aires, Argentina, ⁴⁰IRCCS Galeazzi Orthopedic Institute, Milan, Italy, Milan, Italy, ⁴¹Rheumatology Unit, Hospital Privado Centro Médico de Córdoba, Argentina, Córdoba, Argentina, ⁴²Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, Rheumatology, Malmö, Sweden, Malmö, Sweden, ⁴³Department of Rheumatology, Malmö University Hospital, Lund University, Sweden, Lund, Sweden, ⁴⁴Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy, Udine, Italy, ⁴⁵Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, Mexico, ⁴⁶Federal University of São Paulo, Sao Paulo, Brazil, San Paulo, Brazil, ⁴⁷Sjögren Syndrome Research Group (AGAUR), Barcelona, Spain, ⁴⁸Department of Medicine, University of Barcelona, Barcelona, Spain., Barcelona, Spain

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Antibodies, big data and salivary gland, Sjogren's syndrome

Session Information

Date: Tuesday, November 15, 2016

Title: Sjögren's Syndrome - Poster II: Clinical Science

Session Type: ACR Poster Session C

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

Background/Purpose: To analyse the main characteristics of patients with primary Sjögren syndrome (SjS) with focal lymphocytic sialadenitis (FLS) unrelated to the presence of circulating anti-Ro/La autoantibodies in a large international cohort of patients.

Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry designed, in 2014, to take a “high-definition” picture of the main features of primary SjS at diagnosis by merging international databases including patients fulfilling the 2002 AE classification criteria. Patients came principally from Europe (n=6045), America (n=1134) and Asia (n=940).

Results: The cohort included 7748 (93%) women and 562 (7%) men, with a mean age at diagnosis of primary SS of 53 years. We selected 5245 patients who showed a Chisholm-Mason grade III or IV in minor salivary gland biopsy and that were also tested for Ro/La autoantibodies, and compared the main features at diagnosis between immunonegative patients (n=2073) and those carrying anti-Ro/La antibodies (n=3172). Immunonegative biopsy-proven patients were predominantly White (p<0.001), were 7 years older at diagnosis (57.44 vs 50.74 years, p<0.0001) and had a higher frequency of oral and ocular dryness (p<0.001), a lower frequency of abnormal salivary flows (p=0.046) and parotid scintigraphy (p=0.012), and a lower frequency of ANA (p<0.001), low C3 (p<0.001), low C4 (p<0.001), rheumatoid factor (p<0.001) and cryoglobulinemia (p=0.001) in comparison with Ro/La+ biopsy-proven patients (Figure 1). Abnormal salivary flows, parotid scintigraphy and ANA remained independent variables statistically associated with negative Ro/La autoantibodies after adjusting by age and gender.

Conclusion: Biopsy-proven patients with primary SS without circulating anti-Ro/SSA and anti-La/SSB antibodies have a specific phenotypic profile at diagnosis of the disease, characterized by an older age, a higher frequency of sicca symptoms, a lower frequency of abnormal diagnostic tests and a milder immunological profile. Patients carrying Ro/La autoantibodies are diagnosed earlier in spite of having sicca symptoms less frequently, probably due to the development of extraglandular features.

Disclosure: P. Brito-Zerón, None; N. Acar-Denizli, 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-Pensec, 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; S. Retamozo, 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, None; M. Ramos-Casals, None.

To cite this abstract in AMA style:

Brito-Zerón P, Acar-Denizli N, 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-Pensec V, Bombardieri M, Hofauer B, Bootsma H, Brun JG, Fraile G, Carsons SE, Gheita T, Morel J, Vollenweider CF, Atzeni F, Retamozo S, 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. How Does Primary Sjogren Syndrome Present in Biopsy-Proven Patients without Circulating Ro/La Autoantibodies? Characteristics at Diagnosis of 2073 Patients from the SjöGren Big Data Project [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/how-does-primary-sjogren-syndrome-present-in-biopsy-proven-patients-without-circulating-rola-autoantibodies-characteristics-at-diagnosis-of-2073-patients-from-the-sjogren-big-data-project/. Accessed .

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