Molecular profiling and therapeutic tailoring to address disease heterogeneity in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic, heterogeneous, systemic autoimmune disease characterized by autoantibody production, complement activation, and immune complex deposition. SLE predominantly affects young, middle-aged, and child-bearing women with episodes of flare-up and remission, although it affects males at a much lower frequency (female: male; 7:1 to 15:1). Technological and molecular advancements have helped in patient stratification and improved patient prognosis, morbidity, and treatment regimens overall, impacting quality of life. Despite several attempts to comprehend the pathogenesis of SLE, knowledge about the precise molecular mechanisms underlying this disease is still lacking. The current treatment options for SLE are pragmatic and aim to develop composite biomarkers for daily practice, which necessitates the robust development of novel treatment strategies and drugs targeting specific responsive pathways. In this communication, we review and aim to explore emerging therapeutic modalities, including multiomics-based approaches, rational drug design, and CAR-T-cell-based immunotherapy, for the management of SLE.

Keywords: CAR-T-cell therapy; Multiomics; Personalized medicine; Single-cell transcriptomics; Systemic lupus erythematosus.

Fig. 1

Immunopathogenesis of B cell, T cell, and dendritic cell in lupus. BAFF: B-cell activating factor, APRIL: proliferation-inducing ligand, BCR: B-cell receptor, VAV2: Vav guanine nucleotide exchange factor 2, PLC ý: Phospholipase C gamma 2, TGF-ß: Transforming growth factor beta, TLR: Toll-like receptor, IFN: Interferon, IRF: Interferon regulatory factor

Fig. 2

Illustrate SLE patients with different clinical manifestations. The conventional approach to treating the disease versus the era of molecular and personalized medicine