What question did this study set out to answer?

This study aims to identify distinct subgroups within neuropsychiatric systemic lupus erythematosus (NPSLE) using clustering based on antibody profiles.

April 12, 2026Open Access

Neuropsychiatric systemic lupus erythematosus subtypes identified by unsupervised clustering: A single-center cohort study

Key Points

This study aims to identify distinct subgroups within neuropsychiatric systemic lupus erythematosus (NPSLE) using clustering based on antibody profiles.
Retrospective single-center study of hospitalized SLE patients with neuropsychiatric manifestations.
Collected demographic, clinical, and laboratory data.
Classified patients as NPSLE or non-NPSLE through clinical judgment and excluded alternative causes.
Performed hierarchical cluster analysis to explore associations between autoantibodies and clinical features.
Analyzed 167 patients, with 152 presenting neuropsychiatric manifestations attributed to SLE.
Identified two distinct clusters of NPSLE patients based on antibody profiles.
Cluster 1 (23.7%) showed predominant cerebrovascular injury and higher antiphospholipid antibody positivity.
Cluster 2 (76.3%) exhibited immune-mediated inflammation with notable anti-SSA, anti-dsDNA, and anti-RiboP positivity.

Abstract

Abstract Background and Objectives Neuropsychiatric (NP) manifestations are common, heterogeneous and severe in systemic lupus erythematosus (SLE) patients, with attribution to SLE remaining diagnostically challenging. Traditional classification focuses on clinical syndromes, overlooking neuropsychiatric systemic lupus erythematosus (NPSLE) immunological heterogeneity. To address the heterogeneity of NPSLE, this study aimed to delineate distinct disease subgroups by clustering patients based on their antibody profiles. These subgroups were then evaluated for diferences in clinical presentation and prognosis, to better characterize disease subsets and support individualized approaches to diagnosis and management. Methods This retrospective single-center study included hospitalized SLE patients with NP manifestations, collecting demographic, clinical and laboratory data. Patients were classified as NPSLE or non-NPSLE by clinical judgment after excluding alternative causes. Hierarchical cluster analysis explored autoantibody-clinical feature associations. Results Among the 167 patients analyzed, 152 had NP manifestations attributed to SLE. Central nervous system (CNS) involvement was predominant (89.1%), with seizures, cerebrovascular disease, acute confusional state (ACS), and demyelinating syndrome being most prevalent manifestations. Hierarchical clustering of 152 NPSLE patients identified two subgroups: Cluster 1 (23.7%) demonstrated cerebrovascular injury as the predominant manifestation, with higher positivity rates of antiphospholipid antibodies (APLs) ( P < 0.01) and a higher incidence of cerebrovascular disease ( P < 0.01). Cluster 2 (76.3%) showed immune-mediated inflammatory profile, with higher positivity of anti-SSA ( P < 0.01), antidsDNA ( P < 0.05), and anti-RiboP antibodies ( P < 0.05). Neurological involvement predominantly manifesting as ACS ( P < 0.05), accompanied by a higher frequency of fever and joint involvement. Conclusions In this study, NPSLE exhibited distinct serological profiles and segregated into two immunologically defined clusters, reflecting its clinical and biological heterogeneity, and suggesting that immunological profiling may enhance precise classification and personalized management of affected patients.

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