From the Guidelines
The most specific antibody for Systemic Lupus Erythematosus (SLE) is anti-double-stranded DNA (anti-dsDNA) antibody. This antibody is highly specific for SLE, with specificity rates of 95% or higher, making it one of the most valuable diagnostic markers for the disease 1. Anti-dsDNA antibodies are included in the classification criteria for SLE and are particularly useful because they are rarely found in other autoimmune conditions or in healthy individuals. These antibodies not only help establish the diagnosis of SLE but also correlate with disease activity, especially lupus nephritis. Anti-dsDNA antibody levels often rise during disease flares and may decrease with effective treatment, making them useful for monitoring disease activity and treatment response 1. The presence of these antibodies reflects the fundamental autoimmune pathology of SLE, where the immune system inappropriately targets nuclear components, leading to immune complex formation, deposition in tissues, and subsequent inflammation and organ damage. While other antibodies like anti-Smith (anti-Sm) are also highly specific for SLE, anti-dsDNA remains the most clinically useful specific marker for the disease.
Some key points to consider when using anti-dsDNA antibodies for SLE diagnosis and monitoring include:
- The use of a double-screening strategy with a sensitive assay (such as a last-generation SPA) followed by a confirmatory test (such as CLIFT) to minimize false positive results 1.
- The importance of standardization in anti-dsDNA testing, as different assays may have varying sensitivity and specificity 1.
- The need for clinicians to understand the limitations and potential pitfalls of anti-dsDNA testing, including the possibility of false positive or false negative results 1.
Overall, anti-dsDNA antibodies remain a crucial tool in the diagnosis and management of SLE, and their use should be guided by a thorough understanding of their strengths and limitations, as well as the clinical context in which they are being used 1.
From the Research
Specific Antibodies for Systemic Lupus Erythematosus (SLE)
The most specific antibody for SLE is the anti-Sm (Smith) antibody, which is highly specific for this disease 2, 3, 4.
Characteristics of Anti-Sm Antibodies
- Anti-Sm antibodies are directed against components of U2-U6 small nuclear ribonucleoproteins (snRNPs) known as Smith (Sm) antigen 2.
- The Sm-antigen is composed of at least nine different polypeptides with molecular weights ranging from 9 to 29.5 kDa 2.
- The most SLE-specific Sm-antigen is SmD, which contains symmetrical dimethylarginine, constituting a major autoepitope within the C-terminus of SmD1 and SmD3 2.
Clinical Significance of Anti-Sm Antibodies
- Anti-Sm antibodies have been reported to occur later than other SLE-associated autoantibodies and, on average, around 1 year before the clinical onset of SLE 2.
- The presence of anti-Sm antibodies is associated with disease activity in patients with new-onset SLE 5.
- Monitoring of anti-Sm antibody titer may help assess the disease activity in SLE 5.
Assays for Anti-Sm Antibodies
- Double immunodiffusion (ID) is the most specific of the assays for anti-Sm antibodies 6.
- Counterimmunoelectrophoresis (CIE) can produce nonspecific precipitin lines, and care must be taken to avoid false identification of precipitin lines 6.
- Indirect immunofluorescence is recommended for ANA screening, ID for definitive antibody identification, and CIE for antibody quantification 6.