ANA-The Misunderstood Lab Test

Free Test Summary provided by Quest Diagnostics

Rheumatic autoimmune diseases are conditions in which the immune system attacks the joints and certain organ systems. They are often difficult to diagnose, as their symptoms can be vague, vary from patient to patient, and often overlap.

Diagnosis is most often based on a compilation of symptoms and signs, including clinical information and laboratory test results. Testing for antinuclear antibodies (ANAs) using an immunofluorescence assay (IFA) is a good first approach for laboratory evaluation of patients suspected of having certain autoimmune rheumatic diseases. This clinical education bulletin describes the clinical benefits of a new comprehensive diagnostic test panel offered by Quest Diagnostics. This comprehensive panel, the ANA Screen, IFA, Reflex to Titer/Pattern, and Reflex to the 11 Antibody Cascade including IdentRA® (test code 94954 from Quest), provides differential diagnosis of the 8 most common rheumatic diseases. It starts with the first-line screen test for autoimmune diseases, ANA testing by IFA. Although various platforms can be used to detect ANAs, an IFA with HEp-2 cells remains the gold standard endorsed by the ACR because of its high sensitivity for several of the autoimmune rheumatic diseases. The high sensitivity stems from the large number of autoantigens, up to 150, in HEp-2 cells. Following a positive ANA IFA screen, the patient sample is tested by 3 tiers of specific autoantibody testing as illustrated in the algorithm.

Given the range of conditions associated with positive ANA IFA results, positive results are not highly specific for any single condition. However, tests for individual rheumatic antibodies may offer greater specificity and are often needed to help establish the diagnosis. The combination of the highly sensitive ANA IFA screen, followed by specific autoantibody testing when the IFA is positive, can help maximize sensitivity as well as specificity—all in a cost-effective manner with one blood draw for the patient. A convenient table summarizes the sensitivity of individual antibodies across disorders.

The ACR guideline for patient testing to screen for RA is just one joint with definitive synovitis over 6 weeks not explained by any other disease. The “IdentRA” components of the test include widely used laboratory markers for rheumatoid arthritis (RA)—rheumatoid factor (RF), cyclic citrullinated peptide (CCP) antibodies11—as well as new serum 14-3-3 eta protein, a biomarker for diagnosis of early RA. Used in conjunction with RF and CCP antibody testing, 14-3-3 eta improves sensitivity for diagnosis of early and established RA by 6%. It is important to know that RF and CCP may be seronegative in 28-44% of RA patients. In 21% to 67% of seronegative RA patients, 14-3-3 eta was found to be positive. Since a positive result for any of these RA markers facilitates timelier diagnosis of RA, concurrent testing can enable prompt initiation of disease-modifying therapy before significant joint erosion develops. RA can be present as a comorbid condition in patients with other autoimmune rheumatic diseases, and also in patients with suspected rheumatic diseases who test negative for ANAs.

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