How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis: analysis of 10,500 patients (Sjögren Big Data Project)

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OBJECTIVES: 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 harmonised 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 fulfillment 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 22 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 hypocomplementaemia and especially cryoglo-bulinaemia 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 ESS- DAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).

CONCLUSIONS: 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 personalised management during the follow-up of patients with primary SjS.


  • Sjögren Big Data Consortium
  • Pilar Brito-Zerón
  • Nihan Acar-Denizli
  • Wan-Fai Ng
  • Margit Zeher
  • Astrid Rasmussen
  • Thomas Mandl
  • Raphaele Seror
  • Xiaomei Li
  • Chiara Baldini
  • Jacques-Eric Gottenberg
  • Debashish Danda
  • Luca Quartuccio
  • Roberta Priori
  • Gabriela Hernandez-Molina
  • Berkan Armagan
  • Aike A Kruize
  • Seung-Ki Kwok
  • Marika Kvarnström
  • Sonja Praprotnik
  • Damien Sène
  • Elena Bartoloni
  • Roser Solans
  • Maureen Rischmueller
  • Yasunori Suzuki
  • David A Isenberg
  • Valeria Valim
  • Piotr Wiland
  • Gunnel Nordmark
  • Guadalupe Fraile
  • Hendrika Bootsma
  • Takashi Nakamura
  • Roberto Giacomelli
  • Valerie Devauchelle-Pensec
  • Andreas Knopf
  • Michele Bombardieri
  • Virginia-Fernandes Trevisani
  • Daniel Hammenfors
  • Sandra G Pasoto
  • Soledad Retamozo
  • Tamer A Gheita
  • Fabiola Atzeni
  • Jacques Morel
  • Cristina Vollenveider
  • Ildiko-Fanny Horvath
  • Kathy L Sivils
  • Peter Olsson
  • Salvatore De Vita
  • Jorge Sánchez-Guerrero
  • Levent Kilic
  • Marie Wahren-Herlenius
  • X. Mariette
  • M. Ramos-Casals
Enheter & grupper
Externa organisationer
  • Hospital CIMA
  • Mimar Sinan Fine Arts University
  • University of Newcastle upon Tyne
  • University of Debrecen
  • Skåne University Hospital
  • University of Paris-Sud
  • University of Pisa
  • University of Strasbourg
  • University Hospital 'Santa Maria della Misericordia'
  • Sapienza University of Rome
  • Hacettepe University
  • University Medical Center Utrecht
  • Catholic University of Korea
  • University Medical Centre Ljubljana
  • Paris Diderot University
  • University of Perugia
  • Vall d'Hebron University Hospital
  • University of Western Australia, Crawley
  • Kanazawa University Hospital
  • University College London
  • Wroclaw Medical Hospital
  • Uppsala universitet, Historiska institutionen
  • Hospital Ramón Y Cajal
  • University of Groningen
  • Nagasaki University
  • University of L'Aquila
  • University Hospital of Brest
  • Technical University of Munich
  • Queen Mary University
  • Federal University of São Paulo
  • Cairo University
  • University of Messina
  • University of Montpellier
  • University of Bergen
  • Haukeland University Hospital
  • Karolinska University Hospital
  • Karolinska Institute
  • Federal University of Espírito Santo
  • Oklahoma Medical Research Foundation
  • Anhui Provincial Hospital
  • Christian Medical College & Hospital
  • University of São Paulo
  • National University of Cordoba, Argentina
  • Hospital Aleman, Buenos Aires
  • University of Barcelona
  • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Reumatologi och inflammation
Sidor (från-till)S102-S112
Antal sidor11
TidskriftClinical and Experimental Rheumatology
Volym36 Suppl 112
StatusPublished - 2018 aug 30
Peer review utfördJa