From the Guidelines
Anti-double-stranded DNA (anti-dsDNA) antibodies have a sensitivity of 70-80% and specificity of 95-98% for systemic lupus erythematosus (SLE), as reported in the most recent study 1. These antibodies are particularly associated with lupus nephritis and disease activity. The sensitivity and specificity of anti-dsDNA antibodies can vary depending on the testing method used, with Crithidia luciliae immunofluorescence and ELISA being common methods 1. Anti-centromere antibodies (ACA) have a sensitivity of 60-80% and specificity of 96-98% for limited cutaneous systemic sclerosis (formerly CREST syndrome), but lower sensitivity (20-30%) for diffuse systemic sclerosis 1. When both antibodies are positive in a patient, this suggests an overlap syndrome, most commonly between SLE and systemic sclerosis. The presence of anti-dsDNA antibodies typically indicates active SLE requiring immunosuppressive therapy, while anti-centromere antibodies suggest a better prognosis compared to other systemic sclerosis-associated antibodies but higher risk for pulmonary hypertension. Some key points to consider when interpreting anti-dsDNA and anti-centromere antibody results include:
- The reference method for anti-dsDNA detection is considered the Farr assay, but this assay is not commonly used in clinical practice due to its limitations 1.
- A double-screening strategy using a last-generation SPA in the first place and, subsequently, the CLIFT as the confirmation test is recommended for anti-dsDNA testing 1.
- Results obtained with each method should be reported explaining their significance and clinical relevance 1. It is essential to consider the clinical context and other laboratory results when interpreting anti-dsDNA and anti-centromere antibody results, as the presence of these antibodies can have significant implications for diagnosis and treatment 1.
From the Research
Sensitivity and Specificity of Positive Double Stranded DNA and Centromere Antibody
- The sensitivity and specificity of anti-double stranded DNA (anti-dsDNA) antibodies in the diagnosis of systemic lupus erythematosus (SLE) have been evaluated in several studies 2, 3, 4, 5, 6.
- A study published in 2025 found that a magnetic bead-based immunofluorescence assay (IFA) using human-derived double-stranded DNA antigen exhibited improved sensitivity and specificity over chemiluminescent immunoassay (CIA) using the WHO reference reagent 2.
- Another study published in 2015 found that the combination of two quantitative methods and the ANA pattern was the most efficient strategy for detecting anti-dsDNA in SLE patients, with a specificity of 100% in patients whose results were positive by all three anti-dsDNA assay methods 3.
- A study published in 2013 found that the specificity of anti-dsDNA was 100% and 97% when using sera from healthy controls and patients with multiple medical problems, respectively 4.
- A review published in 2022 found that anti-dsDNA testing shows considerable variation in test specificity, with potential impact on the management of SLE patients, and that some tests such as the Crithidia luciliae indirect immunofluorescence test (CLIFT) and fluorescence enzyme immunoassay methods are likely to be ≥ 90% specific 6.
- The sensitivity and specificity of centromere antibody were not directly evaluated in the provided studies, but it is known that centromere antibodies are often associated with limited systemic sclerosis and can be used as a diagnostic marker for this condition.
- The studies suggest that the sensitivity and specificity of anti-dsDNA antibodies can vary depending on the test method and population being studied, and that a combination of tests and clinical evaluation may be necessary for accurate diagnosis and management of SLE patients 2, 3, 4, 5, 6.