Natural antibody mediated innate autoimmune response

Area of Science:

• Immunology
• Pathology
• Autoimmunity

Background:

• The innate immune system can target self-antigens, similar to pathogen recognition.
• Ischemia-reperfusion (I/R) injury is a newly identified example of innate autoimmunity.

Purpose of the Study:

• To review the role of natural IgM in initiating innate autoimmunity during I/R injury.
• To identify the self-targets recognized by natural IgM in I/R injury.

Main Methods:

• Review of studies on intestinal, skeletal muscle, and heart I/R models.
• Identification of a monoclonal natural IgM and its corresponding self-targets.

Main Results:

• Reperfusion of ischemic tissues triggers an acute inflammatory response via natural IgM activation of the complement system.
• Non-muscle myosin heavy chain types II A and C identified as self-targets in different tissues.
• IgM binding to ischemic antigen facilitates Mannan-binding lectin (MBL) binding, leading to complement activation and tissue injury.

Conclusions:

• Natural IgM-mediated innate autoimmunity plays a significant role in the pathology of I/R injury.
• Understanding this mechanism offers insights into potential therapeutic strategies for ischemic diseases.