The role of complement in the development of systemic lupus erythematosus

Area of Science:

• Immunology
• Rheumatology
• Genetics

Background:

• The complement system has paradoxical roles in systemic lupus erythematosus (SLE) pathogenesis.
• SLE patients exhibit reduced complement levels and tissue deposition, suggesting a detrimental role.
• Conversely, deficiencies in complement proteins strongly correlate with SLE development.

Purpose of the Study:

• To reconcile the seemingly contradictory roles of complement in SLE.
• To explore hypotheses explaining complement's dual involvement in SLE pathogenesis.

Main Methods:

• Review of existing literature on complement function in SLE.
• Analysis of clinical observations regarding complement levels and deficiencies in SLE patients.
• Examination of proposed hypotheses regarding complement's role in cellular waste disposal and immune cell activation thresholds.

Main Results:

• Two primary hypotheses explain complement's dual role: its involvement in clearing cellular debris and immune complexes, and its influence on B and T lymphocyte activation thresholds.
• Complement deficiency may impair peripheral tolerance maintenance, contributing to SLE.
• Genetic factors likely modulate disease phenotype in complement-deficient individuals.

Conclusions:

• Complement's role in SLE is complex, involving both protective and detrimental functions.
• Understanding these dual roles is crucial for elucidating SLE pathogenesis.
• Further research into the interplay between complement, cellular homeostasis, immune tolerance, and genetics is warranted.