PoM No 5, 2014

Publication of the Month


May 05/14: Usefulness of ANA results from different clinical request levels


Key messages:

  • The prevalence of positive ANA test results increases from primary to secondary to tertiary care patient groupsPositive
  • ANA IIF results are more prone to false interpretation in clinical settings with low pre-test probabilities for Systemic Autoimmune Rheumatic Diseases


Avery TY, van de Cruys M, Austen J, Stals F, Damoiseaux JCMC
Anti-Nuclear Antibodies in Daily Clinical Practice: Prevalence in Primary, Secondary, and Tertiary Care
J Immunol Research 2014, Article ID 401739,http://dx.doi.org/10.1155/2014/401739


Background: For the diagnosis of systemic autoimmune rheumatic diseases (SARD), autoantibodies – particularly anti—nuclear antibodies (ANA) directed against various cellular components including dsDNA and extractable nuclear antigens (ENA) are fundamental. ANA have been traditionally detected by indirect immunofluorescence (IIF) and the American College of Rheumatology recently stated that IIF is still considered the gold standard. However, the specificity of the test is relatively poor with 25-30% of healthy individuals testing positive for ANA at a 1:40 serum dilution and this increases with age. A positive ANA test must therefore always be interpreted cautiously and with a high regard for the clinical context of the patient.

Summary: This study determined the prevalence of ANA in primary (general practice) (6.2% positive ANA in tested cohort), secondary (regional hospital) (10.8% positive in cohort) and tertiary care (university hospital) (16.0% positive in cohort). It also looked at ANA titres and anti-ENA and anti-dsDNA antibodies by further testing all samples positive for ANA by initial IIF screening at 1:80 dilution. The study found that ANA prevalence and titre increase from primary to tertiary care and the prevalence of anti-ENA and anti-dsDNA was significantly higher in both secondary and tertiary care (4.2% and 3.4% of total cohorts respectively) when compared to the primary care cohort (1.3%).

Conclusions: “..in primary care the usage of traditional ANA screening tests is more prone to false interpretation of positive ANA results.” “An alternative testing algorithm for detection of patients with SARD might be more appropriate.”

Comment: A positive ANA result may help the clinician to identify a patient with SARD, but especially in situations with low pre-test probabilities of such diseases, the risk of false interpretations of such a result is high. Of the only 6.2% positive samples from the primary requests, the vast majority (70%) were of low titre (1:80) or were negative for specific antibodies to ENAs and dsDNA (78.9%). The authors suggest some different approaches to reduce the number of positive ANA results lacking clinical significance and their findings support moves to improve the usefulness of ANA testing.


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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.