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Immunoglobulin-G subclasses (IgG1-4)

Category Immunology
Test background

Measuring IgG subclasses are useful in the diagnosis of IgG4 related disease and as a third line investigation of suspected antibody deficiency where total IgG is normal.

IgG4 related diseases (IgG4RD) are fibroinflammatory diseases characterised by infiltration of IgG4 positive plasma cells into the affected tissue and storiform fibrosis. Any organ can be affected but the most common are the salivary glands, pancreas, biliary tract and heart. Patients usually present with mass lesions or organ enlargement. Diagnosis by tissue biopsy is the gold standard as around a quarter of patients with IgG4RD will have serum IgG4 within the normal range. For these patients an IgG4:IgG ratio over 10% may be found. The degree of IgG4 elevation correlates with the number of organs involved and predicts relapse rate. For those with elevated IgG4 this test can be used to monitor response to therapy. Around 30% of IgG4RD patients additionally have elevated IgE and eosinophilia (Lanzillotta M, et al. BMJ. 2020 Jun 16;369:m1067).

Most patients with selective IgG subclass deficiency are asymptomatic. Isolated IgG1 deficiency is almost always seen in association with reduced serum IgG levels so is not considered a subclass deficiency. Patients with IgG2 deficiency who fail to make appropriate antibody responses to pneumococcus and other polysaccharide encapsulated micro-organisms have an increased risk of upper airway bacterial infections. IgG2 deficiency can occur alongside IgG4 deficiency and can be found in IgA deficient patients with recurrent infection. In some patients selective IgG subclass deficiency with IgA deficiency can progress to combined variable immune deficiency (CVID). There is very limited evidence that isolated IgG3 deficiency is associated with disease and IgG4 levels are known to be low or absent in up to 25% of Caucasians.

This test is performed by turbidimetry.

Clinical Indications

Investigation of pancreatic disease, retroperitoneal fibrosis, parotid /salivary disease
Investigation of known IgA deficient patients with recurrent infection or specific antibody deficiency with normal total immunoglobulins

Reference range
IgG1: 3.2-10.2 g/L
IgG2: 1.2-6.6 g/L
IgG3: 0.2-1.9 g/L
IgG4: 0-1.3 g/L

Please note, values for children vary according to age.
Reference ranges are manufacturer derived and were verified in house

Sample & container required Serum (RST rust top)
Sample volume 5-10 mL blood (2 mL serum)
Turnaround time 14 days