Anti-ssDNA Is Not a Useful Diagnostic Test



Anti-ssDNA Is Not a Useful Diagnostic Test

Testing for antibodies against nuclear antigens can be helpful in the diagnosis of diseases such as systemic lupus erythematosus and scleroderma. The National Consensus Conference on Guidelines for ANA testing was published by Kavanaugh et al. in January, 2000.1 Those Guidelines stress that improper use of ANA testing can lead to misinformation, incorrect diagnoses, and a waste of limited revenue for testing.

Although kits are available for anti-ssDNA and some laboratories offer this testing, it is not useful in the diagnosis of specific autoimmune diseases and is not mentioned as being part of the testing that should be done as a follow-up to a positive ANA in the new Guidelines. Although this testing is offered by some clinical laboratories, it is not useful in the diagnosis of SLE or other conditions due to its nonspecificity.2

The problem with anti-ssDNA testing is not new. Several years go, Koffler et al. noted that biochemically the ssDNA molecule itself has a tendency to react nonspecifically with proteins.3 Further, antibodies to dsDNA may cross-react with ssDNA making the interpretation of a positive anti-ssDNA problematic at best. Attempts to remove anti-dsDNA by solid-phase DNA may not remove the anti-dsDNA antibodies that cross-react with the ssDNA backbone determinants.3

Clinically the presence of anti-ssDNA is highly nonspecific. Yes, they occur in patients with systemic lupus erythematosus (SLE). However, they are also found in controls, nonrheumatic diseases, and many other rheumatic diseases.2,4 Clinically the presence or absence of these antibodies can rule nothing in and nothing out.

The new Guidelines for ANA testing suggested use of some tests for specific autoantibodies when working up patients suspected of having an autoimmune disease. As mentioned above, they do not recommend the use of anti-ssDNA. They recommend using tests to detect antibodies to dsDNA, Sm, nRNP, Ro (SS-A), La (SS-B), Scl-70, and Jo-1 as follow-ups to a positive ANA screening test in the appropriate clinical setting. Use of one or two specific autoantigen tests is preferred to the “shotgun” approach where all of these autoantibodies are sought in a large panel. The Guidelines point out that large panel testing has the problems of increased costs and erroneous diagnosis. The latter results from the false positive rates of the various tests that are not needed. For instance, if one wished to obtain supportive laboratory information for a diagnosis of systemic lupus erythematosus, one may wish to perform anti-dsDNA, anti-Sm and possibly anti-Ro (SS-A). There would be no use in performing Scl-70, nRNP, La (SS-B) or Jo-1 in such a patient. Anti-ssDNA is positive in about 70% of these patients, but it does not add any specificity to the diagnosis. Further, if the anti-ssDNA were positive and the other assays were negative, it would not add substantially to the evidence that the patient has SLE because anti-ssDNA is found in so many other conditions.

Therefore, the Diagnostic Immunology Resource Committee (DIRC) considers the use of anti-ssDNA assays to be of research interest only and not of practical utility for clinical diagnosis. Inclusion of this test on our diagnostic panel provides a misimpression that the CAP DIRC supports the use of the test for clinical diagnosis. We do not. Therefore, it will no longer be offered beginning in year 2001 for the Immunology (Special) Survey S2.

David F. Keren, MD

Diagnostic Immunology Resource Committee

References

1. Kavanaugh A, et al. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. Arch Pathol Lab Med. 2000;124:71.

2. Hahn BH. Antibodies to DNA. N Engl J Med. 1998;338:1359-1368.

3. Koffler D, Miller TE, Faiferman I. Antipolynucleotide antibodies: the rheumatic connection. Human Pathol. 1983;14:406-418.

4. Bradley J, McCluskey J. Clinical Immunology. Oxford, England: Oxford University Press; 1997:339-341.

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download