Concise Review for Primary-Care Physicians
Use and Interpretation of Rheumatologic Tests: A Guide for Clinicians

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In recent years, several new autoantibody tests have been developed and are being used in the field of rheumatology, including the antineutrophil cytoplasmic antibody (ANCA) and myositis-specific antibodies such as anti-Jo1. Positive test results for ANCAs reveal one of two basic staining patterns: cytoplasmic (c-ANCA) or perinuclear (p-ANCA). The Jol anti-body test is often helpful at the time of diagnosis of a new case of idiopathic inflammatory myopathy. Herein this article reviews the clinical utility of the new tests in conjunction with the established autoantibody tests including antinuclear antibodies and extractable nuclear antibodies. Both the antinuclear antibody and extractable nuclear antibody tests are helpful in diagnosing connective tissue diseases. Before the results of any of these tests can be interpreted, the physician must consider the sensitivity, specificity, and negative and positive predictive values. Positive results must be analyzed in the clinical context and in relationship to other autoantibody test results.

Section snippets

Antinuclear Antibodies

One of the hallmarks of autoimmune disorders, including systemic lupus erythematosus (SLE) and many other connective tissue diseases (CTDs), is the formation of autoanti&x00AD;bodies.2 The antinuclear antibody (ANA) test is widely available and uses an indirect immunofluorescence technique that detects antibodies that bind to various nuclear antigens.

The ANA test is very sensitive for SLE; more than 95&x0025; of patients with SLE have positive results (Table 1). It is not specific, however, for

Anti-Dsdna Antibodies

A much more specific but less sensitive testing strategy for SLE is the finding of anti-dsDNA antibodies. The test can be performed by using several methods including the enzyme-linked immunosorbent assay technique. Increased levels of anti-dsDNA antibodies are evident in up to 70&x0025; of patients with SLE. The presence of anti-dsDNA antibodies tends to correlate with renal disease. Additionally, the level of anti-dsDNA antibodies tends to correlate with disease activity in some patients with

Other Autoantibodies

Antibodies to single-stranded DNA are nonspecific and have limited clinical utility. Anti-histone antibodies occur in up to 95&x0025; of cases of drug-induced SLE but may occur in more than 50&x0025; of cases of idiopathic SLE; thus, the presence of this antibody is occasionally less helpful than its absence. The appropriate clinical setting for drug-induced SLE involves a patient exposed to an agent known to cause drug-induced SLE, usually with a high-titer positive ANA, ab&x00AD;sence of

Scleroderma Antibodies

An anti-centromere staining pattern can be found on an ANA test in about 80&x0025; of patients with the limited variant of scleroderma, the so-called CREST (calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) syndrome. The test result is usually reported as positive or negative without a titer. This antibody can also be detected in up to 25&x0025; of patients with idiopathic Raynaud's phenomenon. Whether the presence of this antibody in a patient

Extractable Nuclear Antibodies

Extractable nuclear antibodies (ENAs) may also be identified in patients with a CTD. Four autoantibodies, directed against ribonuclear proteins (RNA), can be detected with commonly available laboratory kits that often use an immunoblot technique. These antibodies are directed against several small nuclear ribonucleoproteins involved in RNA processing. In general, results of these tests are reported as either positive or negative without titers. These antibodies are helpful in diagnosis but are

Rheumatoid Factor

Serum rheumatoid factors (RFs) are detected in about 80&x0025; of patients with rheumatoid arthritis (RA). They are frequently present in patients with Sjogren's syndrome and less commonly in patients with other CTDs.7 Occasionally, they occur in patients without CTD, including those with chronic infections, especially subacute bacterial endocarditis and gammopathies.

Most RFs are IgM autoantibodies directed against the “FC” portion of IgG immunoglobulins. Several methods are used for their

Antineutrophil Cytoplasmic Antibodies

Antineutrophil cytoplasmic antibodies (ANCAs) are recently discovered antibodies directed against several neutrophil cytoplasmic components.8,9 These antibodies are detected by using an immunofluorescence technique. Positive test results for ANCAs reveal one of two basic patterns of staining: cytoplasmic (c-ANCA) or perinuclear (p-ANCA).

The c-ANCA indicates the presence of antibodies directed against proteinase 3. A positive c-ANCA test result is specific and sensitive for the presence of

Jo1

Recently, a new group of antibodies referred to as myositisspecific antibodies have been discovered that occur in up to 50&x0025; of patients with idiopathic inflammatory myopathy (IIM), including polymyositis and dermatomyositis.&x00A0;These antibodies allow better classification of patients in terms of both clinical features and prognosis (Table 2). Currently, the only clinically available antibody is the anti-Jo1. This antisynthetase antibody is directed against transfer-RNA histydyl

Conclusion

Selecting the appropriate autoantibody test in patients with suspected rheumatologic disorders should be guided by the clinical setting. Before ordering the test, the physician should have a clear indication of and anticipated response to the test result. Usually, the best approach is to begin with sensitive tests, and if the results are positive, tests that are specific may be obtained to help confirm the diagnosis. For example, if SLE is suspected on the basis of clinical features such as

Questions About Rheumatologic Testing

(See article, pages 391 to 396)

  • 1.

    Which one of the following statements is true about autoantibody testing in patients with systemic lupus erythematosus (SLE)?

    • a.

      The double-stranded DNA level may fluctuate with disease activity

    • b.

      A positive antinuclear antibody (ANA) test result is very specific for SLE

    • c.

      The ANA is not sensitive for SLE

    • d.

      Anti-Sm antibodies are present in most patients with SLE

    • e.

      A positive test result for UIRNP antibody seldom occurs in patients with SLE

  • 2.

    Which one of the

Correct answers

1. a, 2. b, 3. C, 4. d, 5. e

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