Complement, complosome, and complotype: A perspective

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Single-cell "omic" technologies reveal immune cell roles in health and disease.
• The complement system, traditionally extracellular, is now recognized for intracellular functions.
• Intracellular complement (the complosome) is a critical regulator of normal cell physiology.

Purpose of the Study:

• To summarize known activation modes and functions of the intracellular complement system (complosome).
• To provide perspective on the origins of intracellular complement.
• To advocate for assessing the complosome alongside the complotype and in patients with complement deficiencies.

Main Methods:

• Review of existing literature on complement system biology.
• Analysis of recent advances in "omic" technologies and immunology.
• Conceptual framework for understanding intracellular complement functions.

Main Results:

• The complosome is an emerging area in complement biology, with significant roles in cell physiology.
• Intracellular complement activation and function are distinct from extracellular pathways.
• The complotype, a measure of inherited complement gene variants, may extend to intracellular components.

Conclusions:

• The discovery of the complosome opens new avenues for understanding immune responses and cell function.
• Further investigation into intracellular complement is crucial for understanding health and disease.
• Reassessing patients with serum complement deficiencies for complosome perturbations may yield new insights.