From the Guidelines
For IgG4-related disease, the primary laboratory test to draw is serum IgG4 level, as elevated levels support the diagnosis, although a definitive diagnosis requires a combination of clinical, radiological, and histological findings, as recommended by the international consensus guidelines 1. When evaluating a patient for IgG4-related disease, it is essential to consider a range of laboratory tests to support the diagnosis and assess disease activity. Key tests include:
- Complete blood count
- Comprehensive metabolic panel
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein (CRP)
- Total IgG and IgG subclasses (IgG1, IgG2, IgG3, IgG4)
- Complement levels (C3, C4)
- Rheumatoid factor
- Antinuclear antibodies (ANA) Additionally, organ-specific tests may be necessary depending on the systems involved, such as:
- Pancreatic enzymes (amylase, lipase) for pancreatic involvement
- Liver function tests for hepatobiliary disease
- Kidney function tests (BUN, creatinine) for renal involvement
- Urinalysis with protein measurement if kidney involvement is suspected These tests help establish the diagnosis, assess disease activity, and monitor treatment response, as outlined in the British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis 1. It is crucial to note that while serum IgG4 elevation supports the diagnosis, it is not always present, and a definitive diagnosis typically requires a tissue biopsy showing characteristic histopathological features, including lymphoplasmacytic infiltration, storiform fibrosis, and IgG4-positive plasma cells, as recommended by the international consensus guidelines 1.
From the Research
Laboratory Tests for IgG4 Disease
To diagnose IgG4-related disease, several laboratory tests can be used, including:
- Serum protein electrophoresis to measure IgG subclasses 2
- IgG4 measurement using ELISA or nephelometric assay 3, 4
- Measurement of serum IgG4 concentration to assess disease activity and response to treatment 5, 4
Interpretation of Serum IgG4 Levels
Serum IgG4 levels can be elevated in IgG4-related disease, but also in other conditions such as:
- Eosinophilic granulomatosis with polyangiitis (EGPA) 6
- Lymphoma 2, 6
- Multicentric Castleman disease (MCD) 2, 6
- Carcinomas 3
- Other autoimmune diseases 3
Diagnostic Criteria
A serum IgG4 cutoff of 1.4 g/L can be used to diagnose IgG4-related disease, with a sensitivity of 82.8% and specificity of 84.7% 4. However, a higher cutoff of 2.8 g/L can increase specificity to 96.2% and negative predictive value to 97.7%, but with a lower sensitivity of 56.9% and positive predictive value of 44.5% 4.
Clinical Utility of Serum IgG4 Measurement
Serum IgG4 measurement can be useful in:
- Diagnosing IgG4-related disease 5, 4
- Assessing disease activity and response to treatment 5, 4
- Predicting multi-organ involvement and risk of relapse 4 However, it is essential to consider the limitations of serum IgG4 measurement, including its lack of specificity and potential for false positives 6.