Anti-dsDNA Antibodies

SARDs are a heterogeneous group of disorders characterized by dysregulation of the immune system, which begins to attack the body’s own tissues. Major SARDs include systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and Sjögren’s syndrome. These diseases can affect multiple organs and share common symptoms such as fatigue, fever, joint pain, and skin rashes. Diagnosis relies on a combination of clinical assessment and specific autoantibody tests. Early diagnosis is crucial to initiate appropriate therapy and slow disease progression.

Anti-dsDNA antibodies against double-stranded DNA are a highly specific marker for SLE. As a result, they were included in the 2019 ACR/EULAR classification criteria. In particular, biopsy-proven lupus nephritis with positive results for ANA or anti-dsDNA is sufficient to classify a patient as having SLE, even without any other criteria.

Anti-dsDNAs are pathogenic antibodies, directly implicated in immune-complex formation; titer changes may reflect disease activity, making them useful for longitudinal patient monitoring.

Among the available detection methods, indirect immunofluorescence (IIFT) on Crithidia luciliae is considered one of the most specific. Crithidia is a flagellated protozoan that contains a subcellular organelle called the kinetoplast, rich in circular double-stranded DNA and lacking histone proteins. The absence of other nuclear antigens reduces the risk of cross-reactions, conferring high analytical specificity for high-affinity anti-dsDNA.

As IIFT is less sensitive than solid-phase assays, it is particularly suitable as confirmation test when there is a clinically suspected positivity, or as part of integrated diagnostic algorithms. Major international guidelines recommend the combined use of multiple methods, since each test detects antibody subpopulations that differ in affinity, isotype and complement-binding capacity.