Researchers have identified distinct transcriptomic changes in patients with systemic lupus erythematosus undergoing belimumab therapy, as detailed in a study.
In the study, published in Annals of Rheumatic Diseases, the researchers analyzed RNA sequencing data from 45 paired blood samples collected at baseline and 6 months posttreatment, providing new insights into treatment responses.
Key findings included suppression of pathways associated with B cells, type I/II interferons, and neutrophil activation. The patients achieving Lupus Low Disease Activity State (LLDAS) demonstrated marked downregulation in these pathways alongside reductions in neutrophil populations and upregulation of CD8-positive T-cell abundance. A machine-learning–derived 50-gene panel, featuring markers such as CCL4L2, CARD10, MMP15, and KLRC2, predicted treatment response with 69% accuracy, 60% sensitivity, and 84% specificity.
In the cohort of 58 participants, 53.4% achieved individual LLDAS and SLE Responder Index-4 (SRI-4) targets, whereas 62.1% met either endpoint. Mean SLEDAI-2K scores significantly declined from 8.2 to 4.4 (P < .001), reflecting clinical improvement.
Notably, the patients with insufficient responses showed elevated activity in cell cycle checkpoints, PI3K/Akt/mTOR, and TGF-beta signaling pathways. Transcriptomic profiles of these patients revealed persistent dysregulation in DNA damage response (DDR) and metabolic pathways, underscoring potential mechanisms of resistance to belimumab.
The researchers concluded that while belimumab modulates both innate and adaptive immune pathways, larger studies are needed to validate these biomarkers and refine patient stratification for optimal therapy.
The authors declared having no competing interests.
