A review of advances in the understanding of lupus nephritis pathogenesis as a basis for emerging therapies [version 1; peer review: awaiting peer review]

• Published in: F1000 research Vol. 9; p. 905
• Main Authors: Yung, Susan, Yap, Desmond YH, Chan, Tak Mao
• Format: Journal Article
• Language: English
• Published: England Faculty of 1000 Ltd 2020; F1000 Research Limited; F1000 Research Ltd
• Subjects: Adaptive immunity; Antigens; Arthritis; B-Lymphocytes; Cell proliferation; Clinical trials; Complement activation; Cytokines; Drug development; Drug dosages; End-stage renal disease; Humans; Immunosuppressive agents; Inflammation; Kidney diseases; Ligands; Lupus; Lupus Erythematosus, Systemic - complications; Lupus nephritis; Lupus Nephritis - drug therapy; Lupus Nephritis - pathology; Lymphocytes B; Lymphocytes T; Nephritis; Pathogenesis; Patients; Pharmacogenomics; Proteins; Review; Signal transduction; Systemic lupus erythematosus; T cell receptors; T-Lymphocytes; lupus nephritis; lupus nephritis pathogenesis; B cell depletion; inflammation; emerging therapies
• ISSN: 2046-1402; 2046-1402
• DOI: 10.12688/f1000research.22438.1

Lupus nephritis is an important cause of both acute kidney injury and chronic kidney disease that can result in end-stage renal disease. Its pathogenic mechanisms are characterized by aberrant activation of both innate and adaptive immune responses, dysregulation of inflammatory signaling pathways, and increased cytokine production. Treatment of lupus nephritis remains a challenging issue in the management of systemic lupus erythematosus since the clinical presentation, response to treatment, and prognosis all vary considerably between patients and are influenced by ethnicity, gender, the degree of chronic kidney damage, pharmacogenomics, and non-immunological modulating factors. Elucidation of the various immunopathogenic pathways in lupus nephritis has resulted in the development of novel therapies, including biologics that target specific antigens on B lymphocytes to achieve B cell depletion, agents that modulate B cell proliferation and development, drugs that block co-stimulatory pathways, drugs that target T lymphocytes primarily, and therapies that target complement activation, signaling pathways, pro-inflammatory cytokines, and neutrophil extracellular traps. This review will discuss recent advances in the understanding of disease pathogenesis in lupus nephritis in the context of potential emerging therapies.