Smith Antibody

Serologic tests for autoantibodies, including antinuclear antibodies (ANAs) and antibodies to specific nuclear antigens such as double-stranded DNA (dsDNA), play an important role in the diagnosis of systemic rheumatic diseases. However, test results for autoantibodies alone are insufficient to establish the diagnosis of a systemic rheumatic disease. No tests for autoantibodies should be performed without a clinical evaluation that leads to a presumptive diagnosis.  

The original discovery of ANA was based on indirect immunofluorescence. Immunofluorescent antibody (IFA) is still the most commonly utilized method for detection of antinuclear antibodies. In this method, diluted patient serum is incubated on a slide containing a monolayer of human epithelial cells. If antibody is present, it binds to cell nuclei. After washing, bound antibody is detected by adding fluorescent anti-human IgG. Positive cells demonstrate bright green nuclear fluorescence with a distinct staining pattern.  Patient samples are initially tested at a dilution of 1:40 to 1:160. Positive samples are then diluted and both the fluorescent pattern and titer are reported. The titer is the highest dilution of serum that still shows immunofluorescent nuclear staining.    

Hep-2 cells are the preferred cell line due to their human origin, high mitotic activity, and the ability to induce expression of clinically important antigens. HEp-2 cells have an estimated 100 to 150 antigens, the most of any method, allowing for detection of the greatest number of antibody specificities. 

Specific follow-up tests for antibodies to the following antigens are available: dsDNA, Sm, RNP, SS-A (Ro), SS-B (La,) Scl-70, histones, and Jo-1. With rare exceptions, these tests should not be ordered if the ANA was negative or weakly positive, because less than 5% of patients with ANA titers <1:160 will have positive follow-up tests.

The Sm and nuclear ribonucleoprotein (RNP) antigens are a particulate complex composed of small nuclear RNAs (U-RNAs) and proteins. They are present in subcellular organelles called spliceosomes that are composed of peptide containing small RNAs. This complex has also been referred to as extractable nuclear antigens (ENA), since it is soluble in saline. 

The Sm (Smith) and related nuclear ribonucleoproteins (nRNPs) are targets for autoantibodies in systemic lupus erythematosis (SLE).  Anti-Sm antibodies are only present in 15 to 30% of the patients with SLE, but they are highly specific for SLE. They occur more frequently (60%) in young black females with SLE. They almost never occur in healthy individuals.

Anti-RNP antibodies, which are commonly tested for in conjunction with anti-Sm, are present in 30 to 40% of SLE patients. Sm antibodies may disappear with treatment, while RNP antibodies persist. 

Anti-Sm antibodies may occur together anti-RNP antibodies in some other ANA-associated connective tissue diseases such as mixed connective tissue disease, systemic sclerosis,  and idiopathic inflammatory myopathies.

Anti-Sm antibodies should not be confused with anti-smooth muscle antibodies detected in autoimmune liver disease.

With rare exceptions, these tests should not be ordered if the ANA was negative or weakly positive, because less than 5% of patients with ANA titers <1:160 will have positive follow-up tests.  Sm titers should not be measured as a marker of disease activity or to establish prognosis.

Smith antibodies can be measured by enzyme-linked immunoassay or multiplex flow immunoassay (Bioplex). Results are reported as positive or negative. The reference value is less than 1.0 U, which is a negative result.

Specimen requirement is one plain red top tube of blood.

References

Tan EM, Kunkel HG. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol. 1966;96(3):464-471.

Zieve GW, Khusial PR. The anti-Sm immune response in autoimmunity and cell biology. Autoimmun Rev. 2003;2(5):235-240.

Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019;71(9):1400-1412.

van Beers JJBC, Schreurs MWJ. Anti-Sm antibodies in the classification criteria of systemic lupus erythematosus. J Transl Autoimmun. 2022;5:100155.

Migliorini P, Baldini C, Rocchi V, Bombardieri S. Anti-Sm and anti-RNP antibodies. Autoimmunity. 2005;38(1):47-54