Pathogenesis of lupus nephritis: an update

Area of Science:

• Immunology
• Nephrology
• Autoimmune Diseases

Background:

• Lupus nephritis (LN) is a significant autoimmune condition characterized by a loss of self-tolerance.
• Autoantibodies, particularly those targeting nucleosomes, play a crucial role in the immunopathogenesis of LN.
• The relationship between complement system activation and systemic lupus erythematosus (SLE) is complex and paradoxical.

Purpose of the Study:

• To review the current understanding of disease mediators in lupus nephritis.
• To highlight the pathogenic roles of nephritogenic autoantibodies and their targets.
• To discuss the intricate relationship between complement pathways and SLE.

Main Methods:

• Review of existing literature on lupus nephritis and systemic lupus erythematosus.
• Analysis of the role of autoantibodies, nucleosomes, and apoptosis in disease development.
• Examination of the complement system's involvement, including classic pathway activation and hereditary deficiencies.

Main Results:

• Nephritogenic autoantibodies that cross-react with nucleosomal epitopes are implicated in LN pathogenesis.
• In vivo generation of nucleosomes is linked to apoptosis.
• While immune complex-mediated complement activation causes injury, complement deficiencies increase SLE risk.

Conclusions:

• Understanding the multifaceted roles of autoantibodies, complement, and reactive species is crucial for lupus nephritis management.
• Further research into the paradoxical relationship between complement and SLE may reveal new therapeutic targets.
• The review emphasizes the importance of apoptosis, nucleosomes, and reactive nitrogen/oxygen species in LN pathogenesis.