How Immunological Profile Drives Clinical Phenotype of Primary Sjögren’s Syndrome at Diagnosis: Analysis of 10.500 Patients (Sjögren Big Data Project)

Soledad Retamozo^1,2, Nihan Acar-Denizli³, Wan-Fai Ng⁴, Margit Zeher⁵, Astrid Rasmussen⁶, Thomas Mandl⁷, Raphaele Seror⁸, Xiaomei Li⁹, Chiara Baldini¹⁰, Jacques-Eric Gottenberg¹¹, Debashish Danda¹², Luca Quartuccio¹³, Roberta Priori¹⁴, Gabriela Hernandez-Molina¹⁵, Berkan Armagan¹⁶, Aike A. Kruize¹⁷, Seung-Ki Kwok¹⁸, Marika Kvarnström¹⁹, Sonja Praprotnik²⁰, Damien Sène²¹, Elena Bartoloni²², Roser Solans²³, Maureen Rischmueller²⁴, Yasunori Suzuki²⁵, David A. Isenberg²⁶, Valeria Valim²⁷, Piotr Wiland²⁸, Gunnel Nordmark²⁹, Guadalupe Fraile³⁰, Hendrika Bootsma³¹, Takashi Nakamura³², Roberto Giacomelli³³, Valérie Devauchelle-Pensec³⁴, Andreas Knopf³⁵, Michele Bombardieri³⁶, Virginia Fernandes Trevisani³⁷, Daniel S. Hammenfors³⁸, Sandra G Pasoto³⁹, Tamer A. Gheita⁴⁰, Fabiola Atzeni⁴¹, Jacques Morel⁴², Cristina Vollenveider⁴³, Ildiko-Fanny Horvath⁵, Kathy L. Sivils⁴⁴, Peter Olsson⁴⁵, Salvatore De Vita⁴⁶, Jorge Sánchez-Guerrero⁴⁷, Levent Kilic¹⁶, Marie Wahren-Herlenius⁴⁸, Xavier Mariette⁸, Manuel Ramos-Casals⁴⁹ and Pilar Brito-Zerón^50,51, ¹Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Córdoba, Consejo Nacional de Investigaciones Científicas y Técnicas (INICSA-UNC-CONICET), Cordoba, Argentina, ²Rheumatology Unit, Hospital Privado Universitario de Córdoba, Institute University of Biomedical Sciences University of Córdoba (IUCBC), Cordoba, Argentina, ³Department of Statistics, Faculty of Science and Letters, Mimar Sinan Fine Arts University, Istanbul, Turkey, Istanbul, Turkey, ⁴Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, Newcastle, United Kingdom, ⁵Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, ⁶Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, USA, Oklahoma City, OK, ⁷Department of Rheumatology, Skåne University Hospital, Malmö, Sweden, Lund, Sweden, ⁸Rheumatology department, Center 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, Paris, France, ⁹Department of Rheumatology and Immunology, Anhui Provincial Hospital, Hefei., Hefei, China, ¹⁰Rheumatology Unit, University of Pisa, Pisa, Italy, ¹¹Rhumatologie, Hôpitaux universitaires de Strasbourg, Strasbourg, France, ¹²Clinical Immunology & Rheumatology, Christian Medical College, Vellore, India, Vellore, India, ¹³Clinic of Rheumatology, Department of Medical Area (DAME), University Hospital “Santa Maria della Misericordia”, Udine., Udine, Italy, ¹⁴Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome., Rome, Italy, ¹⁵Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico City, Mexico, ¹⁶Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey, ¹⁷Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands, ¹⁸Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul., Seoul, Korea, Republic of (South), ¹⁹Unit of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ²⁰Department of Rheumatology, University Medical Centre, Ljubljana., Ljubljana, Slovenia, ²¹Lariboisière Hospital, Paris Diderot University, Paris, France, ²²Rheumatology Unit, University of Perugia, Perugia, Italy, ²³Department of Internal Medicine, Hospital Vall d’Hebron, Barcelona, Barcelona, Spain, ²⁴The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia, ²⁵Ishikawa, Division of Rheumatology, Kanazawa University Hospital, Kanazawa, Ishikawa, Ishikawa, Japan, ²⁶Centre for Rheumatology Research, University College Hospital London, UK, London, United Kingdom, ²⁷Department of Medicine, Federal University of Espírito Santo and University Hospital HUCAM/EBSERH, Vitória, Vitoria, Brazil, ²⁸Department of Rheumatology and Internal Medicine, Wroclaw Medical Hospital, Wroclaw, Wroclaw, Poland, ²⁹Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, ³⁰Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Madrid, Spain, ³¹Department of Rheumatology & Clinical Immunology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands, ³²Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ³³Clinical Unit of Rheumatology, University of l’Aquila, School of Medicine, L’Aquila, L’Aquila, Italy, ³⁴Rheumatology Department, Brest University Hospital, Brest, Brest, France, ³⁵Otorhinolaryngology/ Head and Neck Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany, ³⁶Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, United Kingdom, ³⁷Federal University of São Paulo, São Paulo, Brazil, ³⁸Department of Rheumatology, Haukeland University Hospital, University of Bergen, Bergen, Norway, ³⁹Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil, ⁴⁰Rheumatology Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt, ⁴¹IRCCS Galeazzi Orthopaedic Institute, Milan, and Rheumatology Unit, University of Messina, Messina, Italy, ⁴²Department of Rheumatology, Montpellier University Hospital and University of Montpellier, Montpellier, France, ⁴³German Hospital, Buenos Aires, Buenos Aires, Argentina, ⁴⁴Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma, OK, ⁴⁵Department of Rheumatology, Skane University Hospital Malmö, Lund University, Malmö, Malmö, Sweden, ⁴⁶Clinic of Rheumatology, Department of Medical Area (DAME), University Hospital “Santa Maria della Misericordia”, Udine, Udine, Italy, ⁴⁷Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico, Mexico, ⁴⁸Department of Medicine, Solna, Unit of Experimental Rheumatology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ⁴⁹University of Barcelona, Hospital Clínic, Barcelona, Barcelona, Spain, ⁵⁰Sjögren’s Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic, Barcelona, Bercelona, Spain, ⁵¹Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA Sanitas, Barcelona, Barcelona, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Clinical, immunoregulation and phenotypes, Sjogren's syndrome

Session Information

Date: Tuesday, October 23, 2018

Title: 5T110 ACR Abstract: Sjögren's Syndrome–Basic & Clinical Science (2880–2885)

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjögren’s syndrome (SjS).

Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonized data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfilment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.

Results: By January 2018, the participant centres had included 10,500 valid patients from 23 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti-La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementemia and especially cryoglobulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for cryoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESSDAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).

Conclusion: we confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalized management during the follow-up of patients with primary SjS.

Disclosure: S. Retamozo, None; N. Acar-Denizli, None; W. F. Ng, None; M. Zeher, None; A. Rasmussen, None; T. Mandl, None; R. Seror, None; X. Li, None; C. Baldini, None; J. E. Gottenberg, None; D. Danda, None; L. Quartuccio, None; R. Priori, None; G. Hernandez-Molina, None; B. Armagan, None; A. A. Kruize, None; S. K. Kwok, None; M. Kvarnström, None; S. Praprotnik, None; D. Sène, None; E. Bartoloni, None; R. Solans, None; M. Rischmueller, None; Y. Suzuki, None; D. A. Isenberg, Merck Serono, Astra Zenica, Janssen, Celgene, Sanofi,, 5; V. Valim, None; P. Wiland, None; G. Nordmark, None; G. Fraile, None; H. Bootsma, None; T. Nakamura, None; R. Giacomelli, None; V. Devauchelle-Pensec, None; A. Knopf, None; M. Bombardieri, None; V. Fernandes Trevisani, None; D. S. Hammenfors, None; S. G. Pasoto, None, 2; T. A. Gheita, None; F. Atzeni, None; J. Morel, None; C. Vollenveider, None; I. F. Horvath, None; K. L. Sivils, None; P. Olsson, None; S. De Vita, None; J. Sánchez-Guerrero, None; L. Kilic, None; M. Wahren-Herlenius, None; X. Mariette, None; M. Ramos-Casals, None; P. Brito-Zerón, None.

To cite this abstract in AMA style:

Retamozo S, Acar-Denizli N, Ng WF, Zeher M, Rasmussen A, Mandl T, Seror R, Li X, Baldini C, Gottenberg JE, Danda D, Quartuccio L, Priori R, Hernandez-Molina G, Armagan B, Kruize AA, Kwok SK, Kvarnström M, Praprotnik S, Sène D, Bartoloni E, Solans R, Rischmueller M, Suzuki Y, Isenberg DA, Valim V, Wiland P, Nordmark G, Fraile G, Bootsma H, Nakamura T, Giacomelli R, Devauchelle-Pensec V, Knopf A, Bombardieri M, Fernandes Trevisani V, Hammenfors DS, Pasoto SG, Gheita TA, Atzeni F, Morel J, Vollenveider C, Horvath IF, Sivils KL, Olsson P, De Vita S, Sánchez-Guerrero J, Kilic L, Wahren-Herlenius M, Mariette X, Ramos-Casals M, Brito-Zerón P. How Immunological Profile Drives Clinical Phenotype of Primary Sjögren’s Syndrome at Diagnosis: Analysis of 10.500 Patients (Sjögren Big Data Project) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/how-immunological-profile-drives-clinical-phenotype-of-primary-sjogrens-syndrome-at-diagnosis-analysis-of-10-500-patients-sjogren-big-data-project/. Accessed .

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