By DoM Communications | Date published: August 13, 2026

Roberto Caricchio and Colleagues Study How B-Cell-Directed Therapy Acts in Systemic Lupus Erythematosus 

In a recent study published in Annals of the Rheumatic Diseases, Roberto Caricchio, MD, the Myles J. McDonough Chair in Rheumatology, professor of medicine, chief of the Division of Rheumatology, and director of the Lupus Center at UMass Chan, and his colleagues reframe how B-cell-directed therapy may act in systemic lupus erythematosus. Using RNA sequencing of negatively selected neutrophils from seven patients with SLE and seven healthy controls, the team identified 258 differentially expressed genes that stably distinguish SLE neutrophils, with intrinsic upregulation of interferon and DNA damage repair programs and downregulation of ribosomal protein genes. These signatures persisted across ex vivo culture and lipopolysaccharide stimulation, indicating a hardwired transcriptomic state rather than a transient response to circulating inflammation. 

The central finding comes from longitudinal sampling of a patient with refractory SLE treated with anti-CD19 CAR T-cell therapy. By three months post-treatment, the neutrophil transcriptome had realigned with healthy controls, evidence of an immune reset extending well beyond the targeted B-cell compartment. This suggests CD19 CAR T-cell therapy reprograms innate immunity through the adaptive arm, a mechanism not previously demonstrated at the transcriptomic level. 

The intrinsic 258-gene signature now anchors preliminary data for an NIH grant application from the lab, supporting a broader program on innate-adaptive crosstalk and therapeutic immune reset in SLE.