This is Part One of a two-part series. Part Two, on rheumatoid factor and anti-cyclic-citrullinated peptide, will appear in the April issue of The Rheumatologist.
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Explore This IssueFebruary 2009
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Laboratory testing is an essential element in the diagnosis and management of patients with rheumatic disease. This article focuses on a diverse array of serological markers that can provide unique information on the status of the patient’s immune system that is important in clinical evaluation as well as scientific inquiry. These tests help in the diagnosis of a particular disease and, importantly, they may help monitor disease activity. Indeed, immunological testing represents one of the bedrocks of rheumatology and is a distinguishing feature of our specialty.
While there are many available tests, the approach to serology follows the traditional approach of any laboratory study. Critical in the interpretation of any serological test is determining its sensitivity (e.g., that proportion of patients with the target disorder who have a positive test), specificity (e.g., that proportion of patients who are free of the target disorder and have negative or normal test results), and positive and negative predictive values, which calculate the likelihood that disease is present or absent based on test results using the test’s sensitivity, specificity, and the probability of disease before the test is performed (pretest probability). This review will cover data on antinuclear antibodies (ANAs).
ANAs are the signature autoantibodies of the rheumatic disease and are tested in many clinical scenarios.1-3 These antibodies are usually detected by immunofluorescent (IF) techniques, utilizing Hep-2 cell lines, and specific antinuclear antibodies are detected by solid-phase immunoassays—for instance, an ELISA. The IF ANA is generally screened at a dilution (e.g., titer) of 1:40, and, if positive, serial dilutions are carried out until a dilution is negative. Most labs titer to 1:1280, but some go higher. It is not clear whether titering higher is clinically useful, because the titer of an ANA usually does not correlate with clinical activity.
The IF ANA test is especially useful as an initial screen for patients suspected of having systemic lupus erythematosus (SLE). ANA testing is also useful for the evaluation of patients with other suspected rheumatic conditions including Sjögren’s syndrome, mixed connective tissue disease (MCTD), drug-induced lupus erythematosus, dermato/polymyositis, scleroderma, adult and juvenile arthritis, and autoimmune hepatitis. However, the presence of an ANA does not signify the presence of illness, because these antibodies may also be found in otherwise normal individuals. As shown in Table 1 (see p. 17), the sensitivity of the ANA for a particular autoimmune disease can vary widely.