The Role of IgG4 in Autoimmunity and Rheumatic Diseases

Area of Science:

• Immunology
• Rheumatology
• Pathology

Background:

• Immunoglobulin G4 (IgG4) is the least common IgG subclass, generally considered non-inflammatory and tolerance-inducing.
• In IgG4-related disease (IgG4-RD), IgG4 exhibits a pathogenic role, contributing to fibrinogenesis and inflammation.
• The role of IgG4 in allergic diseases, particularly the IgE/IgG4 ratio, is well-established.

Purpose of the Study:

• To review current knowledge on IgG4 beyond IgG4-related disease.
• To emphasize the role of IgG4 in various autoimmune diseases, especially rheumatic conditions.
• To explore the involvement of IgG4 in malignancies and infections.

Main Methods:

• Literature review of existing research on IgG4.
• Analysis of studies investigating IgG4 levels and function in different diseases.
• Synthesis of findings related to IgG4's pathogenic and marker roles.

Main Results:

• Elevated IgG4 levels are observed in rheumatoid arthritis, though not consistently linked to disease activity.
• IgG4's role in Sjogren's syndrome is under investigation, with potential significance for both elevated and decreased levels.
• Anti-nuclear IgG4 antibodies are found in SLE patients, potentially influencing complement consumption and cytokine production.

Conclusions:

• IgG4 is implicated in the pathogenesis of various autoimmune diseases, including rheumatic conditions, pemphigus, and myasthenia gravis.
• IgG4 may play a role in helminth infections and certain malignancies like melanoma and cholangiocarcinoma.
• Further research is needed to fully elucidate IgG4's complex functions and potential as a diagnostic or prognostic marker across diverse diseases.