Three clinical and immunological phenotypes of systemic lupus erythematosus onset identified through clustering analysis: data from the RELES registry
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Systemic lupus erythematosus (SLE) shows heterogeneous clinical expression at onset, complicating early characterisation and risk assessment. We aimed to identify SLE phenotypes emerging after diagnosis and assess their clinical relevance. Methods We analysed newly diagnosed SLE patients from the Spanish multicentre RELES inception cohort. Eighteen binary clinical and immunological variables based on the 2019 EULAR/ACR classification criteria, cumulatively recorded within two years of diagnosis, were included. Multiple correspondence analysis followed by unsupervised hierarchical clustering on principal components with k-means consolidation was performed. Internal validation metrics assessed cluster stability and separation. Baseline characteristics, treatments and early clinical burden were compared across clusters. Results A total of 795 patients were included (87.7% women; mean age at diagnosis 42 ± 16 years). Three clinically interpretable phenotypes were identified. Cluster 1 ( n = 168, 21.1%) represented a renal-dominant phenotype, characterised by younger age, frequent lupus nephritis, complement consumption and greater exposure to intensive immunosuppression, with the highest rates of infections and cumulative damage. Cluster 2 ( n = 175, 22.0%) showed a haematologic-serosal phenotype, with cytopenias, serositis, and frequent antiphospholipid and anti-dsDNA positivity, also associated with substantial early damage. Cluster 3 ( n = 452, 56.9%) represented a mild cutaneous-articular phenotype, with lower serological activity and the lowest burden of early complications. Internal validation supported a stable three-cluster solution, with moderate separation reflecting the continuum of early SLE. Conclusion Three clinically meaningful SLE phenotypes can be identified within two years of diagnosis using routinely collected variables. This approach may provide a practical framework for early disease characterisation and risk-adapted management in SLE.
Source: Arthritis Research & Therapy
Authors: Andrés González-García, Martin Fabregate, Guillermo Ruiz-Irastorza, Carlos Feijoo-Massó, María López-Paraja, Olga Capdevila Pons, Manuel Anselmo Bahamonde García, Nuria Navarrete, Olga Araujo, Aleida Martínez Zapico, Sandra Parra Pérez, Borja Gracia-Tello, María Victoria Villalba García, Ángel Robles Marhuenda, Mónica Angerri, Eva Fonseca Aizpuru, Miguel López Dupla, Iñigo Les Bujanda, Alba Gil, Germán Daroca Bengoa, Mercedes Pérez-Conesa, Ana Isabel García Sánchez, Isabel Perales Fraile, María López Veloso, Javier de la Hera, María Calabuig Ballester, Alba Jerez Lienas, María Andreo, Eva Calvo Begueria, Begoña Frutos, Antonio Chamorro, Sara Gómez-García, Salvador García Morillo⁶, Arnau Antoli Gil, Gerard Espinosa Garriga⁸, Joan Duran Bertran, Antoni Castro Guardiola, Isabel Sánchez-Berná⁷, Laura Pérez Abad, Paula Martínez García, María Dolores Manjón Rodríguez, Ivan Cusacovich
Institutions: Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, University of the Basque Country, Corporació Sanitària Parc Taulí, Institute of Research and Innovation Parc Tauli, Bellvitge University Hospital, Hospital Universitario Virgen del Rocío, Complejo Hospitalario Universitario de Granada, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Hospital Universitario Central de Asturias, Institut de Recerca Biomèdica Catalunya Sud, Hospital Universitari Sant Joan de Reus, Universitat Rovira i Virgili, Hospital Clínico Universitario Lozano Blesa, Hospital Universitario La Paz, Hospital Universitari de Girona Doctor Josep Trueta, Hospital Universitario De Cabueñes, Hospital Universitari Joan XXIII de Tarragona, Universidad de Navarra, Hospital San Pedro, Hospital Universitario Miguel Servet, Hospital Universitario Infanta Leonor, Hospital Universitario Infanta Sofía, Hospital Universitario de Burgos, Hospital Universitari i Politècnic La Fe, University Hospital Mútua de Terrassa, Mútua Terrassa, Universitat de Miguel Hernández d'Elx, Hospital General San Jorge, Hospital Universitario de Fuenlabrada, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca, Hospital Clínico Universitario de Valladolid, Complejo Hospitalario de Jaén
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,690
OpenAlex ID: W7214448457
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