Early decrease of T-bet+ B cells during subcutaneous belimumab predicts response to therapy in systemic lupus erythematosus patients

Francesca La Gualana; Giulio Olivieri; Begi Petriti; Licia Picciariello; Francesco Natalucci; Maddalena Sciannamea; Laura Gragnani; Umberto Basile; Milvia Casato; Francesca Romana Spinelli; Lucia Stefanini; Stefania Basili; Marcella Visentini; Fulvia Ceccarelli; Fabrizio Conti

doi:10.1016/j.imlet.2024.106962

Early decrease of T-bet⁺ B cells during subcutaneous belimumab predicts response to therapy in systemic lupus erythematosus patients

Immunol Lett. 2024 Dec 4:272:106962. doi: 10.1016/j.imlet.2024.106962. Online ahead of print.

Authors

Affiliations

¹ Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.
² Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome.
³ Lupus Clinic, Rheumatology, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Viale del Policlinico 155 00161 Rome, Italy.
⁴ Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Pisa, Italy.
⁵ Department of Clinical Pathology, Santa Maria Goretti HospitalAUSL Latina, Latina, Italy.
⁶ Department of Translational and Precision Medicine, Sapienza University, Rome, Italy. Electronic address: [email protected].

PMID: 39643119
DOI: 10.1016/j.imlet.2024.106962

Abstract

Systemic lupus erythematosus (SLE) is characterized by B cell dysregulation and expansion of atypical B cells that may correlate with disease manifestations and activity. This study investigated the impact of subcutaneous (sc) Belimumab (BLM) on the peripheral B cell compartment and on the functional properties of CD21^low, T-bet⁺ and CD11c⁺ atypical B cells, in 21 active SLE patients over a 12-month period. At baseline, active SLE patients displayed reduced unswitched IgM memory B cells and expansion of atypical B cells, compared to healthy donors and to SLE patients in remission. sc BLM therapy promptly restored B cell homeostasis with a reduction of T-bet⁺ B cells, observed early in patients responsive to therapy. These findings highlight the pathogenic role of T-bet⁺ B cells in SLE disease and suggest their potential utility as biomarker of clinical response.

Keywords: Belimumab; Biomarker; Systemic lupus erythematosus; T-bet(+) B cells.