What is the most sensitive test for Systemic Lupus Erythematosus (SLE)?

From the Guidelines

The most sensitive test for Systemic Lupus Erythematosus (SLE) is the antinuclear antibody (ANA) test, which has a sensitivity of approximately 95-99%. This means that nearly all patients with SLE will have a positive ANA result, as noted in the study by 1. The test works by detecting antibodies that bind to components within the cell nucleus, which are commonly produced in autoimmune conditions like SLE. A positive ANA is typically reported as a titer (such as 1:80,1:160, etc.) with higher titers generally suggesting a stronger autoimmune response.

Key Points to Consider

• The ANA test is highly sensitive but lacks specificity, as positive results can occur in other autoimmune diseases, certain infections, medications, and even in approximately 5-15% of healthy individuals, as discussed in 1 and 1.
• Therefore, a positive ANA alone is not sufficient for diagnosing SLE and must be considered alongside other clinical features and more specific antibody tests like anti-dsDNA and anti-Smith antibodies, which have higher specificity for SLE.
• For proper diagnosis, physicians typically follow the American College of Rheumatology or SLICC classification criteria, which incorporate laboratory findings with clinical manifestations, as mentioned in 1 and 1.
• The use of a double-screening strategy using a last-generation solid-phase assay (SPA) in the first place and, subsequently, the Crithidia luciliae immunofluorescence test (CLIFT) as the confirmation test for anti-dsDNA antibodies is recommended, as outlined in 1.

Clinical Application

• The ANA test should be used as an initial screening tool due to its high sensitivity, but clinicians must be cautious of its low specificity.
• When a positive ANA result is obtained, further testing with more specific antibodies such as anti-dsDNA should be considered, especially in the context of high clinical suspicion for SLE, as suggested by 1 and 1.
• The choice of assay for anti-dsDNA detection should consider the clinical context, with the Farr assay and CLIFT offering high clinical specificity, as noted in 1.

From the Research

Most Sensitive Test for SLE

• The antinuclear antibody (ANA) test is considered the most sensitive test for SLE, with a sensitivity of 91.75% 2 and 98% 3.
• The sensitivity of ANA in diagnosing SLE was also reported to be 95.36% when combined with anti-ds-DNA antibody 2.
• Another study reported that the ANA test is the most sensitive test for SLE and is therefore the best screening assay for ruling out its presence 4.

Comparison of Sensitivity and Specificity

• The sensitivity and specificity of ANA, anti-ds-DNA antibody, complement C3, and complement C4 were analyzed in one study, with results showing:
  • ANA: 91.75% sensitivity and 79.65% specificity
  • Anti-ds-DNA antibody: 67.01% sensitivity and 98.23% specificity
  • Complement C3: 87.11% sensitivity and 82.74% specificity
  • Complement C4: 88.66% sensitivity and 77.43% specificity 2
• Another study reported the sensitivity and specificity of ANA and anti-ds-DNA in the diagnosis of SLE, using control sera obtained from healthy individuals and patients with multiple medical problems, with results showing:
  • ANA: 98% sensitivity and 92% specificity (using healthy controls)
  • ANA: 90% sensitivity and 96% specificity (using a titer of ≥ 1:160)
  • Anti-ds-DNA: 100% specificity (using healthy controls) and 97% specificity (using patients with multiple medical problems) 3

Clinical Significance of Anti-Sm Antibodies

• Anti-Sm antibodies are essential for the diagnosis of SLE, especially in anti-ds-DNA-negative patients 5.
• The sensitivity of anti-Sm antibodies was reported to be 25.9% at a specificity of 99% 5.
• Anti-Sm antibodies were associated with age, the number of ACR criteria, and cross-sectional disease activity 5.