Complement and systemic lupus erythematosus

Area of Science:

• Immunology
• Rheumatology

Background:

• The complement system is a critical component of innate immunity.
• Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with complex pathogenesis.
• The role of complement in SLE has been described as paradoxical, acting as both a protective and detrimental factor.

Purpose of the Study:

• To review the multifaceted role of the complement system in the pathogenesis of SLE.
• To explore the complex relationship between complement activation, deficiency, and autoantibody production in SLE.
• To present hypotheses explaining the dual role of complement in SLE.

Main Methods:

• Literature review of complement's involvement in SLE.
• Analysis of genetic associations between complement deficiencies and SLE susceptibility.
• Examination of complement's role in SLE effector mechanisms and autoantibody responses.

Main Results:

• Homozygous deficiencies in classical complement pathway proteins are linked to SLE susceptibility.
• Complement proteins deposit in inflamed tissues during SLE flares.
• Inhibition of C5 has shown therapeutic potential in murine SLE models.
• Autoantibodies against complement proteins, notably C1q, are associated with severe SLE manifestations like glomerulonephritis.

Conclusions:

• The complement system significantly influences SLE pathogenesis through both protective and pathogenic mechanisms.
• Complement deficiencies predispose individuals to SLE, while its activation contributes to disease progression and inflammation.
• Anti-C1q autoantibodies are a marker of severe SLE and indicate a complex interplay between autoantibodies and the complement system.