Pitfalls of autoimmune serologic testing Save

Misuse of laboratory testing may lead to misdiagnoses and mismanagement; this is particulary prevalent when clinicians consider the use of the diagnostic use of  serological autoimmune markers. 

A current review focuses commonly used serologies and autoimmune tests to identify common pitfalls and a diagnostic workflow when suspecting systemic autoimmune diseases.

Practical points from this review: 

• Laboratory markers should be used to support a clinical diagnosis, rather than be the sole method of establishing a diagnosis
• The value of a diagnostic test is strongly dependent on the reasons for ordering that test.  Value is best with a high probability based on history and examination.
• Mass screening for autoimmune disease or connective tissue disease(s) is not recommended
• Approximately 10–20% of healthy individuals may test positive for ANA depending on the titer [[8], [9], [10]]. It remains unclear whether these individuals will subsequently develop an autoimmune disease.
• ANA positivity appears to have a heritability of roughly 25% (without a future risk of lupus)
• ACPA: Present also before disease onset. Specific for RA; they may be present even when the patient does not meet yet the criteria for RA
• Positive ENA antibodies do not represent always the presence of an autoimmune disease, as these commercially available ENA assays  have variable sensitivity and specificity
• ENA testing should not be done in the presence of ANA negativity
• IIF is essential (preferred) to verify the true presence of anti-dsDNA antibodies; ELISA may be more suitable for monitoring dsDNA changes
• ANA and anti-ENA titers tend to remain stable, but anti-dsDNA levels may fluctuate according to disease activity
• anti-thyroid peroxidase and anti-thyroglobulin antibodies are often the sole explanation for ANA positivity (typically with a speckled or homogeneous pattern)
• SPEP: patients presenting with polyclonal gammopathy should be evaluated for chronic infections or autoimmune diseases. The gamma region reflects indeed the immunoglobulin production, including autoantibodies
• C3 & C4 may be low in SLE but also in cryoglobulinemia and hereditary angioedema