The Role of IgG4 in Disease Diagnostics

Immunoglobulin G4 (IgG4) is a subclass of immunoglobulin G (IgG) that plays a unique role in the immune system. Unlike other IgG subclasses, IgG4 is characterized by its limited ability to activate complement pathways and its unique structural properties that allow for dynamic rearrangements of its Fab arms. These features enable IgG4 to act as a modulator of immune responses, making it a key molecule of interest in various disease states and a valuable biomarker in disease diagnostics.

IgG4 and its Unique Characteristics

IgG4 is involved in immune tolerance and regulation. It is produced in response to chronic antigen exposure and is particularly prominent in conditions requiring immune tolerance, such as allergies and parasitic infections. One of its defining features is the ability to exchange Fab arms, resulting in functionally monovalent antibodies. This limits the formation of immune complexes and inflammatory responses, which can be beneficial in some contexts but problematic in others.

IgG4 in Disease Diagnostics

1. IgG4-Related Disease (IgG4-RD):

IgG4-RD is a systemic fibroinflammatory condition characterized by elevated serum IgG4 levels and IgG4-positive plasma cell infiltration in affected tissues. Common examples include autoimmune pancreatitis and Mikulicz’s disease. Quantifying serum IgG4 levels and identifying IgG4-positive cells through immunohistochemistry are critical diagnostic tools for this disease.

2. Autoimmune Disorders:

In some autoimmune conditions, such as pemphigus vulgaris, elevated IgG4 levels are observed due to chronic immune stimulation. IgG4 autoantibodies may serve as both pathogenic agents and diagnostic markers, helping clinicians differentiate these conditions from other similar diseases.

3. Allergic Responses:

IgG4 is often elevated in individuals undergoing allergen immunotherapy or those with high antigen exposure. Monitoring IgG4 levels can provide insights into the efficacy of allergen-specific immunotherapy and the development of immune tolerance.

4. Oncology and Tumor Microenvironment:

Emerging evidence suggests that IgG4 plays a role in cancer biology. Tumors can exploit IgG4’s anti-inflammatory properties to evade immune responses. Elevated IgG4 levels in the tumor microenvironment may serve as a diagnostic and prognostic marker in certain cancers.

Diagnostic Techniques

Several advanced methods are used to measure IgG4 levels and identify its role in diseases:

• Serum IgG4 Quantification: Enzyme-linked immunosorbent assays (ELISA) are commonly used to measure serum IgG4 levels.
• Immunohistochemistry: Tissue biopsies stained for IgG4-positive plasma cells aid in diagnosing IgG4-RD.
• Flow Cytometry: Used to identify IgG4-secreting B cells and plasma cells in blood and tissue samples.

Conclusion

IgG4 serves as a critical biomarker in a variety of diseases, particularly in IgG4-related disease, autoimmune disorders, and allergy management. Its unique structural and functional properties offer valuable insights into disease mechanisms and therapeutic interventions. Continued research into IgG4 will further expand its utility in disease diagnostics, providing clinicians with precise tools for diagnosis and monitoring.

ICL manufactures anti-Human IgG4 Antibody (Mouse Clone #1F12) - Monoclonal along with monoclonal and polyclonal antibodies to Human IgA / IgE / IgG / IgM / Kappa / Lambda. In addition, we manufacture Human IgG4 Fc - Recombinant.

About ICL: ICL is a U.S.-based manufacturer of biochemical reagents and life science products. With over 45 years serving the biotech industry, ICL has developed a strong relationship with the world’s leading research institutions, in vitro diagnostics (IVD) manufacturers, and biopharma companies. Offering in-house research and development services, ICL also provides custom solutions to serve research teams and IVD companies whose needs go beyond the industry standard.