Spanish study identifies three distinct early SLE phenotypes

Researchers analyzing data from the Spanish multicentre RELES inception cohort have identified three distinct clinical and immunological phenotypes of systemic lupus erythematosus (SLE) onset. The study, published in Arthritis Research & Therapy, utilized clustering analysis on newly diagnosed patients to characterize the heterogeneous nature of the disease within two years of diagnosis. This approach aims to provide a practical framework for early disease characterisation and risk-adapted management, addressing the complexity that often complicates early risk assessment in SLE patients.

The study focused on 795 newly diagnosed SLE patients, a population that was predominantly female, with 87.7% of participants being women. The mean age at diagnosis was 42 years, with a standard deviation of 16 years. By examining this specific cohort, the researchers sought to understand how clinical and immunological variables emerge shortly after the initial diagnosis.

The analytical methodology involved the use of eighteen binary clinical and immunological variables. These variables were based on the 2019 EULAR/ACR classification criteria and were cumulatively recorded within two years of the patients’ diagnosis. The research team performed multiple correspondence analysis followed by unsupervised hierarchical clustering on principal components. To ensure the robustness of the identified groups, k-means consolidation was applied. Internal validation metrics were then used to assess the stability and separation of the resulting clusters, providing a statistical basis for the distinct phenotypes identified in the data.

The analysis revealed three clinically interpretable phenotypes that differed significantly in their clinical and immunological profiles. The first group, designated as Cluster 1, comprised 168 patients, representing 21.1% of the total cohort. This cluster was characterized by a renal-dominant phenotype. Patients in this group tended to be younger and experienced frequent lupus nephritis. They also showed signs of complement consumption and required greater exposure to intensive immunosuppressive treatments.

The second phenotype, Cluster 2, included 175 patients, accounting for 22.0% of the study population. This group displayed a haematologic-serosal phenotype. Key features of this cluster included cytopenias and serositis. Immunologically, patients in Cluster 2 frequently tested positive for antiphospholipid antibodies and anti-dsDNA antibodies.

The third and largest group, Cluster 3, consisted of 452 patients, making up 56.9% of the cohort. This cluster represented a mild cutaneous-articular phenotype. Compared to the other two groups, patients in Cluster 3 exhibited lower serological activity.

Internal validation of the clustering model supported the stability of the three-cluster solution. The separation between the clusters was described as moderate, which the authors noted reflects the continuum of early SLE.

The study concludes that three clinically meaningful SLE phenotypes can be identified using routinely collected variables within two years of diagnosis.

Subject of Research: Identification of three clinical and immunological phenotypes of systemic lupus erythematosus onset using clustering analysis in the RELES registry.

Article Title: Three clinical and immunological phenotypes of systemic lupus erythematosus onset identified through clustering analysis: data from the RELES registry

Article References: González-García, A., Fabregate, M., Ruiz-Irastorza, G., Feijoo-Massó, C., López-Paraja, M., Pons, O. C., García, M. A. B., Navarrete, N., Araujo, O., Zapico, A. M., Pérez, S. P., Gracia-Tello, B., García, M. V. V., Marhuenda, Á. R., Angerri, M., Aizpuru, E. F., Dupla, M. L., Bujanda, I. L., Gil, A., … Cusacovich, I. (2026). Three clinical and immunological phenotypes of systemic lupus erythematosus onset identified through clustering analysis: data from the RELES registry. Arthritis Research & Therapy. https://doi.org/10.1186/s13075-026-03908-5

Image Credits: AI Generated

DOI: 10.1186/s13075-026-03908-5

Keywords: systemic lupus erythematosus, SLE phenotypes, RELES registry, clustering analysis, lupus nephritis, EULAR/ACR criteria, inception cohort, clinical immunology, risk assessment, early diagnosis, Three, clinical