The complement system in inflammatory bowel disease: from early observations to emerging frontiers

Area of Science:

• Innate immunity
• Complement system biology
• Gastrointestinal immunology

Background:

• The complement system, an evolutionarily conserved innate immunity component, is increasingly recognized for its role in intestinal inflammation.
• Historical observations of complement deposition and elevated levels in IBD patients have evolved into a complex understanding of its functions.
• Recent research highlights the dichotomous role of complement in IBD, acting as both protective and pathogenic.

Purpose of the Study:

• To review recent advances in complement biology relevant to IBD.
• To examine how complement influences intestinal immune responses during inflammation.
• To discuss the therapeutic implications of complement's role in IBD.

Main Methods:

• Review of recent scientific literature on complement system and IBD.
• Analysis of findings from genome-wide association studies.
• Synthesis of current understanding of complement's protective and pathogenic roles.

Main Results:

• The complement system comprises over 60 proteins involved in host defense.
• Local synthesis and activation of complement components occur at mucosal sites, including the colon.
• Genetic variants in complement genes are associated with severe IBD complications.
• Complement exhibits a dual role in IBD: excessive activation exacerbates inflammation, while impaired function worsens disease outcomes.

Conclusions:

• Complement-targeted therapies have shown success in other diseases but not yet in IBD.
• Further research into the context-dependent protective and pathogenic functions of complement is necessary.
• Developing effective future therapeutic strategies for IBD requires a deeper understanding of complement's intricate roles.