Immunoglobulin G4 (IgG4) is the least abundant of the four IgG subclasses, normally representing less than 5% of total IgG. It has gained clinical significance primarily through its association with IgG4-related disease (IgG4-RD), a systemic fibroinflammatory condition that can affect almost any organ in the body.
IgG4-related disease is characterised by dense infiltration of IgG4-positive immune cells into affected tissues, causing swelling, fibrosis, and organ dysfunction. The pancreas is one of the most commonly affected organs (autoimmune pancreatitis), but IgG4-RD can also involve the bile ducts, salivary glands, kidneys, thyroid, lungs, aorta, and retroperitoneal tissues. The condition can mimic malignancy and other autoimmune diseases, making accurate investigation important.
Elevated serum IgG4 supports the clinical suspicion of IgG4-RD when interpreted alongside imaging and clinical findings. However, an elevated IgG4 alone does not confirm the condition. Around 30% of biopsy-confirmed IgG4-RD cases have normal serum IgG4, and mild IgG4 elevations can occur in many other inflammatory, autoimmune, and allergic conditions. Tissue biopsy remains the gold standard for definitive diagnosis.
This test is almost exclusively ordered in specialist settings by gastroenterologists, rheumatologists, or clinical immunologists investigating suspected IgG4-RD or autoimmune pancreatitis. It is not a routine screening test. The result is interpreted as part of a broader workup that includes imaging, clinical presentation, and often histopathology.
It is worth noting that serum IgG4 measured here is different from food-specific IgG4 testing marketed for food intolerance. Those tests are not validated for diagnosing food sensitivities and serve a different purpose entirely.
To investigate suspected IgG4-related disease (IgG4-RD), autoimmune pancreatitis, and other conditions associated with IgG4-positive infiltration of organs, as part of a specialist workup.
