Anti-Smith Antibodies Are an Important Part of Systemic Lupus Erythematosus Classification Criteria

Antibodies attacking Antigen
Antibodies attacking Antigen
Study authors discussed the characteristics of the Smith antigen, its role in SLE classification, and the test methods available to detect them.

Anti-Smith (Sm) antibodies are an important component of previous and current systemic lupus erythematosus (SLE) classification criteria, according to review findings published in Journal of Translational Autoimmunity.

Anti-Sm antibodies are found in 5% to 30% of individuals, depending on the test method used and ethnicity. Anti-Sm antibodies are very specific to patients with SLE and are often present before diagnosis. However, the processes behind the formation of anti-Sm antibodies and their clinical significance remains unclear.

Despite their recognized importance in classification criteria, there is no defined test prescribed for screening anti-Sm reactivity in patients with SLE. Widely-used tests in daily practice include both indirect immunofluorescence tests (IIFT) and antigen-specific immunoassays, such as enzyme-linked immunosorbent assays, addressable laser bead immunoassays, line immunoassays, chemiluminescent immunoassays, and fluorescent enzyme immunoassays.

According to the review authors, any positive antinuclear antibody test should be followed-up to confirm the presence of anti-Sm antibodies using an IIFT or connective tissue disease screen. The gold standard technique for anti-Sm antibody detection is radioactive immunoassay.

However, the specificity, sensitivity, and accuracy of immunoassays is dependent on the source of antigen used and how it is coated to the solid surface used in the test. Therefore, comparing test results from different laboratories is challenging as each test manufacturer specifies their own cutoff values. The authors of the review recommended using test result-specific likelihood ratios to overcome some of these differences.

The authors concluded, “For optimal interpretation of anti-Sm test results, that currently lack harmonization, it is important that both laboratory specialists and clinicians communicate and are both aware of the impact of the choice of anti-Sm assay and the way results are reported.”


van Beers JJBC, Schreurs MWJ. Anti-Sm antibodies in the classification criteria of systemic lupus erythematosus. J Transl Autoimmun. Published online April 13, 2022. doi:10.1016/j.jtauto.2022.100155