Immunoglobulin G Subclass 4 (IgG4)

Immunoglobulin G Subclass 4 (IgG4)

IgG4 is a unique subclass of Immunoglobulin G (IgG) that plays a specialized role in immune regulation and tolerance. Unlike other IgG subclasses, IgG4 is weakly pro-inflammatory and is involved in modulating immune responses, making it important in chronic antigen exposure and certain immune disorders.

Key Features of IgG4:

1. Least Abundant IgG Subclass – Accounts for only 3–6% of total IgG in the blood.
2. Weak Complement Activation – Unlike IgG1 and IgG3, which strongly activate the complement system, IgG4 has minimal inflammatory activity.
3. Dynamic Structure – IgG4 undergoes Fab-arm exchange, meaning its two antigen-binding arms can swap with another IgG4 molecule, making it functionally monovalent and less effective at cross-linking antigens.
4. Involved in Immune Tolerance – IgG4 is often associated with chronic antigen exposure, such as in allergy desensitization therapy and repeated parasite infections.

Functions of IgG4:

✅ Regulation of Chronic Inflammation – Helps reduce excessive immune responses, particularly in conditions with prolonged antigen exposure.
✅ Tolerogenic Role – Increased in allergy immunotherapy, reducing allergic reactions over time.
✅ Weak Effector Functions – Does not strongly activate the complement system or trigger immune cell killing, unlike other IgG subclasses.

Clinical Importance of IgG4:

🔹 IgG4-Related Disease (IgG4-RD) – A chronic autoimmune condition where IgG4 levels are elevated, leading to inflammatory tissue fibrosis (e.g., IgG4-related pancreatitis, sclerosing cholangitis).
🔹 Allergy Tolerance Marker – Increased IgG4 is linked to successful allergy desensitization therapy.
🔹 Elevated IgG4 Levels – Seen in chronic infections, autoimmune diseases, and certain cancers.
🔹 IgG4 Deficiency – Can contribute to recurrent bacterial infections (e.g., sinusitis, pneumonia) due to impaired immune responses.

Comparison of IgG4 with Other IgG Subclasses: