Review

Using the Antinuclear Antibody Test to Diagnose Rheumatic Diseases: When Does a Positive Test Warrant Further Investigation?

Authors: Elizabeth R. Volkmann, MD, Mihaela Taylor, MD, Ami Ben-Artzi, MD

Abstract

The anti-nuclear antibody (ANA) test is ordered commonly as a screening test for rheumatic diseases. Although ANA positivity is highly sensitive for certain rheumatic diseases, the presence of ANA is nonspecific and can be associated with numerous nonrheumatic factors, including environmental exposures, malignancies, drugs, and infections. This article describes a practical approach for physicians when evaluating patients using a positive ANA test. In the absence of connective tissue disease symptoms, the ANA test has minimal clinical significance in diagnosing rheumatic diseases. Understanding how to use ANA test results appropriately may reduce unnecessary referrals and costly workups.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Holborow EJ, Asherson GL, Johnson GD, et al. Antinuclear factor and other antibodies in blood and liver diseases. Br Med J 1963; 9: 656–658.
 
2. Moore AE, Sabachewsky L, Toolan HW. Culture characteristics of four permanent lines of human cancer cells. Cancer Res 1955; 15: 598–602.
 
3. Gniewek RA, Stites DP, McHugh TM, et al. Comparison of antinuclear antibody testing methods: immunofluorescence assay versus enzyme immunoassay. Clin Diagn Lab Immunol 1997; 4: 185–188.
 
4. Fritzler MJ, Wiik A, Tan EM, et al. A critical evaluation of enzyme immunoassay kits for detection of antinuclear autoantibodies of defined specificities. III. Comparative performance characteristics of academic and manufacturers’ laboratories. J Rheumatol 2003; 30: 2374–2381.
 
5. Meroni PL, Schur PH. ANA screening: an old test with new recommendations. Ann Rheum Dis 2010; 69: 1420–1422.
 
6. Tan EM, Feltkamp TE, Smolen JS, et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 1997; 40: 1601–1611.
 
7. Li QZ, Karp DR, Quan J, et al. Risk factors for ANA positivity in healthy persons [published online ahead of print]. Arthritis Res Ther 2011; 13: R38.
 
8. Lahita RG, Chiorazzi N, Gibofsky A, et al. Familial systemic lupus erythematosus in males. Arthritis Rheum 1983; 26: 39–44.
 
9. Farnam J, Lavastida MT, Grant JA, et al. Antinuclear antibodies in the serum of normal pregnant women: a prospective study. J Allergy Clin Immunol 1984; 73: 596–599.
 
10. Alves MF, Fraiji NA, Barbosa AC, et al. Fish consumption, mercury exposure and serum antinuclear antibody in Amazonians. Int J Environ Health Res 2006; 16: 255–262.
 
11. Covini G, von Muhlen CA, Pacchetti S, et al. Diversity of antinuclear antibody responses in hepatocellular carcinoma. J Hepatol 1997; 26: 1255–1265.
 
12. Timuragaoglu A, Duman A, Ongut G, et al. The significance of autoantibodies in non-Hodgkin’s lymphoma. Leuk Lymphoma 2000; 40: 119–122.
 
13. Thomas PJ, Kaur JS. Antinuclear, antinucleolar and anticytoplasmic antibodies in patients with malignant melanoma. Cancer Res 1983; 43: 1372–1382.
 
14. Berlin T, Zandman-Goddard G, Blank M, et al. Autoantibodies in nonautoimmune individuals during infections. Ann N Y Acad Sci 2007; 1108: 584–593.
 
15. Katz U, Zandman-Goddard G. Drug-induced lupus: an update. Autoimmun Rev 2010; 10: 46–50.
 
16. Bossuyt X, Hendrickx A, Frans J. Antinuclear antibody titer and antibodies to extractable nuclear antigens. Arthritis Rheum 2005; 53: 987–988.
 
17. Khan S, Alvi A, Holding S, et al. The clinical significance of antinucleolar antibodies. J Clin Pathol 2008; 61: 283–286.
 
18. Solomon DH, Kavanaugh AJ, Schur PH. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. American College of Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines. Arthritis Rheum 2002; 47: 434–444.
 
19. Baturone R, Soto MJ, Márquez M, et al. Health-related quality of life in patients with primary Sjögren’s syndrome: relationship with serum levels of proinflammatory cytokines. Scand J Rheumatol 2009; 38: 386–389.
 
20. Wigley FM. Raynaud’s phenomenon. N Engl J Med 2002; 347: 1001–1008.
 
21. Spencer-Green G. Outcomes in primary Raynaud phenomenon: a meta-analysis of the frequency, rates, and predictors of transition to secondary disease. Arch Intern Med 1998; 158: 595–600.
 
22. Maricq HR, LeRoy EC. Patterns of finger capillary abnormalities in connective tissue disease by “wide-field” microscopy. Arthritis Rheum 1973; 16: 619–628.
 
23. Wijeyesinghe U, Russell AS. Outcome of high titer antinuclear antibody positivity in individuals without connective tissue disease: a 10-year follow-up. Clin Rheumatol 2008; 27: 1399–1402.
 
24. Peene I, Meheus L, Veys EM, et al. Detection and identification of antinuclear antibodies (ANA) in a large and consecutive cohort of serum samples referred for ANA testing. Ann Rheum Dis 2001; 60: 1131–1136.
 
25. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349: 1526–1533.