The human factor H protein family - an update

Area of Science:

• Immunology
• Complement System
• Protein Function

Background:

• The complement system is a crucial immune network involved in both physiological and pathological processes.
• Proper regulation of complement activation is essential to prevent detrimental effects.
• Factor H is a primary regulator, with its splice variant and related proteins (FHRs) also implicated in disease.

Purpose of the Study:

• To provide an updated overview of the Factor H protein family, including Factor H, FHR-like protein 1, and FHR proteins.
• To elucidate the biological functions of FHR proteins, which are less characterized than Factor H.
• To highlight recent advancements in studying and characterizing these complement-regulating proteins.

Main Methods:

• Review of existing literature on Factor H and FHR proteins.
• Analysis of current evidence regarding their roles in complement activation and immune cell modulation.
• Discussion of emerging tools for protein distinction, quantification, and functional characterization.

Main Results:

• Factor H is a well-studied inhibitor of complement activation.
• FHR proteins primarily act as enhancers of complement activation and opsonization, counterbalancing Factor H's inhibitory role.
• Both Factor H and some FHR proteins exhibit non-canonical functions, modulating immune cell activity outside the complement cascade.

Conclusions:

• Factor H family proteins play versatile roles in the immune system, acting as key regulators of the complement cascade.
• FHR proteins are emerging as soluble pattern recognition molecules and positive regulators of complement.
• Further research and improved tools are vital for fully understanding the complex functions of Factor H family proteins in health and disease.