Year: 2025
Type: article
Abstract: Description Systemic lupus erythematosus (SLE) manifests as a heterogeneous autoimmune condition. The difficulty in developing targeted therapies for SLE highlights the need for better molecular endotypes. In this study, we integrated peripheral blood single-cell transcriptome datasets (5 datasets, 254 SLE patients, 134 healthy controls, 1.7 million immune cells). Our work builds on a 93 gene-expression score for lupus, called the SLE MetaScore (SMS), defined in bulk transcriptomes. The SMS, computed with pseudobulk gene expression, distinguished patients with SLE from healthy controls with an area under the receiver operating characteristic curve (AUROC) of 0.91 (95% CI: 0.89–0.94), 0.88 (95% CI: 0.85–0.91), and 0.94 (95% CI: 0.91–0.97) in adult European, adult Asian, and pediatric patients, respectively. Next, k-means clustering identified two groups of lupus patients (high vs low) based on the proportion of cells in a SLE state—displaying high or low SMS expression, respectively. Multivariate logistic regression found that the high endotype was associated with presence of anti-Smith, leukopenia, and lymphopenia. The high group had lower proportions of naive CD4+ T cells, with increased regulatory CD4+ T cells and proliferating T/NK cells. Lastly, we found anti-CD19 CAR-T cell therapy reversed the systemic SMS expression across immune cells. This work highlights the potential of better molecular endotyping of lupus to improve disease monitoring and treatment. Topic Categories Basic Autoimmunity (BA)
Source: The Journal of Immunology
Authors: Evan Maestri, Hong Zheng, Purvesh Khatri
Institutions: Stanford Medicine, Stanford University
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416448865
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