Immunological signatures in patients with Sjögren's disease: association with systemic disease activity at diagnosis.

Lucía Delgado, Alejandra Flores-Chávez, Antónia Szántó, Roberta Priori, Heendrika Bootsma, Berkan Armagan, Luca Quartuccio, Sonja Praprotnik, Yasonuri Suzuki, Gabriela Hernandez-Molina, Vasco C Romão, Agata Sebastian, Elena Bartoloni, Maureen Rischmueller, Roser Solans, Sandra G Pasoto, Cecilia Fugmann, Isabel Sánchez Berná, Francesco Carubbi, Virginia Fernandes Moça Trevisani, Valeria Valim, Sheila Melchor, Brenda Maure Noia, Eva Fonseca-Aizpuru, Hideki Nakamura, Miguel López-Dupla, Marcos Vazquez, Miriam Akasbi, Guillem Policarpo Torres, Borja De Miguel Campo, Mihaela Roxana Suru, Carmen Vericat Queralt, Ildiko Fanny Horváth, Ilenia Fischetti, Arjan Vissink, Levent Kilic, Valeria Manfrè, Katja Perdan Pirkmajer, Yuhei Fujisawa, Matilde Bandeira, Krzysztof Proc, Roberto Gerli, Chandra Kirana, Norma Nardi, Manuel Ramos-Casals, Pilar Brito-Zerón

Journal: Clinical and experimental rheumatology 2025;43(12):2124-2132

PMID: 41410589

View on PubMed

Abstract

OBJECTIVES

This study aimed to analyse the relationship between distinct autoantibody combinations (immunological signatures) and systemic disease activity in patients with Sjögren's disease (SjD). The hypothesis was that specific multi-autoantibody signatures would be associated with higher systemic disease activity at diagnosis, serving as predictors of a more severe disease course.

METHODS

A retrospective observational study was conducted using data from the Big Data Sjögren Project Consortium, an international multicentre registry. The serological status (positive/negative) at diagnosis for ANA, RF, anti-Ro, and anti-La was recorded for each patient. Systemic disease activity was assessed using the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and a simplified Disease Activity Score (DAS) categorised as low, moderate, or high. Statistical analyses included pairwise comparisons, a sensitivity analysis grouping signatures by the number of positive antibodies, and demographic-adjusted ordinal models.

RESULTS

Serum autoantibodies were highly prevalent, with over 94% of patients having at least one autoantibody. The mean ESSDAI values varied significantly across signatures. The fully seronegative group had the lowest mean ESSDAI at 3.61, while the fully seropositive group (ANA+/Ro+/La+/RF+) had the highest among common phenotypes, with a mean of 7.93. A strong dose-response relationship was observed, with each additional positive autoantibody associated with a 1.11-point mean increase in ESSDAI and a 35% increase in the odds of being in a higher DAS category. The rarest signatures, such as ANA-/Ro-/La+/RF+, exhibited the highest mean systemic activity (mean 13.20).

CONCLUSIONS

The number and combination of SjD-related autoantibodies at diagnosis are robustly associated with systemic disease activity. Multi-positive profiles, particularly those combining RF with anti-Ro, identify patients at higher risk of systemic activity. Interpreting combined serological patterns offers an immediate, low-cost method for patient stratification and can help guide clinical management.

Address: Autoimmune Diseases Unit, Department of Internal Medicine, Hospital CIMA Sanitas, Barcelona; and Postgraduate Degree in Artificial Intelligence in Medicine, Department of Medicine, University of Barcelona, Spain.; Postgraduate Degree in Artificial Intelligence in Medicine, Department of Medicine, University of Barcelona, Spain.; Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Hungary.; Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome; and Saint Camillus International University of Health Science, UniCamillus, Rome, Italy.; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, the Netherlands.; Division of Rheumatology, Department of Internal Medicine, Hacettepe University, Faculty of Medicine, Ankara, Turkey.; Division of Rheumatology, Department of Medicine, University of Udine, Hospital Santa Maria della Misericordia, ASUFC, Udine, Italy.; Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia.; Division of Rheumatology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.; Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico.; Rheumatology Department, Hospital de Santa Maria, Unidade Local de Saúde Santa Maria and Faculdade de Medicina, Universidade de Lisboa, Lisbon Academic Medical Centre, Lisbon, Portugal.; Department and Clinic of Rheumatology and Internal Medicine, Wroclaw Medical University, Poland.; Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, Italy.; Department of Rheumatology, The Queen Elizabeth Hospital, Discipline of Medicine, University of Adelaide, South Australia, Australia.; Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.; Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Brazil.; Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.; Department of Internal Medicine, Virgen de las Nieves University Hospital, Granada; and ibs.GRANADA Biomedical Research Institute, Granada, Spain.; Department of Clinical Medicine, Life, Health and Environmental Sciences, Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, University of L'Aquila, Italy.; Division of Health Based Evidence, Federal University of São Paulo, Brazil.; Federal University of Espírito Santo, Brazil.; Department of Rheumatology, Hospital 12 de Octubre, Madrid, Spain.; Department of Internal Medicine, Complexo Hospitalario Universitario de Vigo, Spain.; Department of Internal Medicine, Hospital de Cabueñes, Gijón, Spain.; Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan.; Department of Internal Medicine, Hospital Joan XXIII, Tarragona, Spain.; Department of Rheumatology, Hospital de Clínicas, San Lorenzo, Paraguay.; Department of Internal Medicine, Hospital Infanta Leonor, Madrid, Spain.; Department of Internal Medicine, Girona Biomedical Research Institute-IDIBGI, Hospital Universitari Doctor Josep Trueta, Girona, Spain.; Department of Internal Medicine, Hospital 12 de Octubre, Madrid, Spain.; Autoimmune Diseases Unit, Department of Internal Medicine, Hospital CIMA Sanitas, Barcelona, Spain.; Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, Italy.; Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.; Department of Rheumatology, University Medical Centre, Ljubljana; and Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Slovenia.; Postgraduate Degree in Artificial Intelligence in Medicine, Department of Medicine, University of Barcelona; and Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain. [email protected].

DOI: 10.55563/clinexprheumatol/zx7cp9

MeSH Terms: Humans, Sjogren's Syndrome, Retrospective Studies, Female, Male, Middle Aged, Autoantibodies, Severity of Illness Index, Antibodies, Antinuclear, Aged, Registries, Biomarkers, Adult, Rheumatoid Factor, Predictive Value of Tests