Clinical Information

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by circulating autoantibodies to many intracellular targets. Of these autoantibodies, the anti-Smith (Sm) antibody associated with a positivity for antinuclear antibodies (ANA) is one of the earliest to be described.(1) The Sm antigen is a complex molecule consisting of a group of core proteins with molecular weights ranging from 9 to 29.5 kDa [B (B1, 28 kDa), B’ (B2, 29 kDa), N (B3, 29.5 kDa), D1 (16 kDa), D2 (16.5 kDa), D3 (18 kDa), E (12 kDa), F (11 kDa), and G (9 kDa)].(2) Of these core proteins, the B and D polypeptides are frequently targeted by the Sm autoimmune response.(3) The Sm proteins, together with ribonucleoproteins and small nuclear RNA form a RNA-protein complex or small nuclear ribonucleoprotein, which is involved in precursor messenger RNA (mRNA) splicing, a process which ultimately leads to mature mRNA generation.(4)

The presence of antibodies to Sm is specific for SLE with a sensitivity of 5% to 30%.(1) Based on the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for SLE, patients positive for anti-Sm antibodies already fulfil 60% of the criteria required for SLE classification.(5,6) However, anti-Sm antibodies may occur together ribonucleoprotein antibodies in certain ANA-associated connective tissue disease such as mixed connective tissue disease, systemic sclerosis and idiopathic inflammatory myopathies.(7) In a recent study,  patients double-positive for anti-dsDNA and anti-Sm antibodies at the time of the diagnosis of SLE were reported to be at higher risk of flares and may benefit from stringent monitoring and early preventive treatment.(8) In addition, some studies have suggested that positivity for anti-Sm antibody may be dependent on patient’s ethnicity.(8)

In routine clinical practice, antigen-specific (solid-phase) immunoassays such as enzyme-linked immunosorbent assays, addressable laser bead immunoassays, line immunoassays, chemiluminescent immunoassays, BioPlex immunoassay and fluorescent enzyme immunoassays are widely used in determination of anti-Sm antibodies.(6,9) These immunoassays use, either a mixture of (native) Sm antigens or a specific (recombinant) Sm antigen, usually obtained by purification of nuclear extract or produced by in vitro translation, respectively, coated to a solid phase (e.g. plate/well, membrane, bead).(6)  In the past, anti-Sm tests used a mixture of all Sm proteins purified from a native source. These mixtures often also contained other proteins, such as U1-RNP, which must be taken into consideration when interpreting results. Based on the analytical differences in immunoassays for detecting anti-Sm antibodies, the method used for their detection is likely to impact the diagnostic performance characteristics.

For more information see:

Connective Tissue Disease Cascade

First-Line Screening for Autoimmune Liver Disease Algorithm