Stratifying Lupus for Targeted Treatment: Autoantibodies, Multi-Omic Biomarkers, and ADC-Based Therapeutics

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease marked by loss of immune tolerance, broad autoantibody production, and inflammation that can damage multiple organs. Pathogenic autoantibodies and immune complexes drive many disease features, yet patients show strong heterogeneity in clinical course and treatment response. This variability creates a need for robust biomarkers that reflect disease activity, predict flares, and guide therapy selection. At the same time, new targeted approaches are emerging to limit immune injury while reducing systemic immunosuppression. Antibody–Drug Conjugates (ADCs), which deliver potent payloads to selected cell types via antibody targeting, have transformed oncology and are now being explored for immune-mediated diseases. In SLE, ADCs could enable precise depletion or reprogramming of key pathogenic immune cells, aligned with biomarker-informed patient stratification.This Research Topic aims to bridge three fast-moving areas in SLE research: (i) autoantibodies as drivers and readouts of disease, (ii) biomarkers that enable precision monitoring and patient stratification, and (iii) the potential of ADCs as next-generation targeted therapeutics. Despite progress in defining autoantibody profiles and inflammatory pathways, translation into clinically actionable tools remains limited. Biomarkers often lack standardization across cohorts, and their links to organ-specific disease and treatment outcomes need clearer validation. In parallel, ADC concepts for autoimmune disease raise key questions on target selection (cell-surface markers, activated immune subsets), safety (off-target toxicity, infection risk), and fit-for-purpose payloads (cytotoxic vs. immunomodulatory). We seek contributions that connect mechanism to application: identifying biomarker signatures that map to pathogenic cell states and testing how these signatures can guide, monitor, or predict responses to ADC-based interventions. The goal is to define a roadmap for biomarker-driven ADC development in SLE.This Research Topic welcomes manuscripts focused on SLE, autoantibodies/biomarkers, and ADC-enabled precision therapy. Submissions should emphasize mechanistic insight and translational relevance. Key themes include, but are not limited to:- Autoantibody repertoires in SLE (specificities, isotypes, glycosylation, pathogenic mechanisms)- Biomarkers for disease activity, flare prediction, organ involvement (especially lupus nephritis), and treatment response- Multi-omics and single-cell approaches linking biomarkers to immune-cell states and tissue pathology- Standardization, validation, and clinical implementation of biomarker assays (including longitudinal cohorts)- ADC target discovery in SLE (B cells, plasma cells, pDCs, myeloid cells, activated T cells) and rationale for selection- ADC payload strategies for autoimmunity (depletion vs. functional reprogramming) and safety considerations- Preclinical models, translational studies, and early clinical concepts for ADCs in SLETopic editor Dr. Dongxiao Liu is employed by Biocytogen. The other Topic Editor report no competing interests related to this Research Topic. Topic editors: Dongxiao Liu, Wenhai Shao Source: https://www.frontiersin.org/research-topics/78166/stratifying-lupus-for-targeted-treatment-autoantibodies-multi-omic-biomarkers-and-adc-based-therapeutics