What are the diagnostic tests for Systemic Lupus Erythematosus (SLE)?

From the Guidelines

The diagnosis of Systemic Lupus Erythematosus (SLE) relies on a combination of laboratory tests and clinical findings, with antinuclear antibody (ANA) testing as the initial screening test, followed by more specific antibody tests such as anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies, as recommended by recent expert panels 1. The initial screening test for SLE is the ANA test, which has a high sensitivity but low specificity, as noted in recent studies 1. If the ANA test is positive, more specific antibody tests are performed, including anti-dsDNA and anti-Sm antibodies, which are highly specific for SLE, as highlighted in recent research 1. Other useful tests include anti-Ro/SSA, anti-La/SSB, and anti-RNP antibodies, which can help establish the diagnosis and assess disease activity, as discussed in recent expert recommendations 1. Complement levels (C3 and C4) are often decreased during active disease due to consumption in immune complex formation, and complete blood count may reveal cytopenias like leukopenia, lymphopenia, anemia, or thrombocytopenia, as observed in recent clinical studies 1. Urinalysis can detect proteinuria or hematuria indicating lupus nephritis, and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) assess inflammation, with ESR typically elevated while CRP remains normal unless there's infection or serositis, as noted in recent research 1. Kidney function tests, liver function tests, and muscle enzymes may be ordered depending on organ involvement, and imaging studies like chest X-rays or echocardiograms may be needed for specific organ assessment, as recommended by recent expert panels 1. Skin or kidney biopsies can confirm tissue involvement, and anti-dsDNA testing should follow a double-screening strategy using a last-generation SPA in the first place, and subsequently, the CLIFT as the confirmation test, as suggested by recent studies 1. In the event of a negative anti-dsDNA SPA result, a confirmatory CLIFT should be done only when other signs of clinical suspicion are present, as recommended by recent expert recommendations 1. These tests collectively help establish diagnosis, assess disease activity, and monitor treatment response in SLE patients, as discussed in recent clinical studies 1. The use of anti-dsDNA autoantibodies in the diagnosis and follow-up of SLE is recommended by recent expert panels, with a focus on improving diagnosis and monitoring of SLE, as highlighted in recent research 1. The guidelines recommend testing the presence of anti-dsDNA in all ANA-positive cases with clinical suspicion of SLE, and anti-dsDNA testing should be used to monitor disease activity, as suggested by recent studies 1. A quantitative assay should be used, preferably with the same method used in the diagnosis and performed by the same laboratory, as recommended by recent expert recommendations 1. The CLIFT assay may be used for confirmation purposes and to ascertain a potential clinical correlation, as noted in recent research 1. In summary, the diagnosis and management of SLE require a comprehensive approach that includes laboratory tests, clinical findings, and expert recommendations, as discussed in recent clinical studies 1. The use of anti-dsDNA autoantibodies is a crucial component of this approach, and recent expert panels have provided recommendations for their use in the diagnosis and follow-up of SLE, as highlighted in recent research 1. By following these recommendations and using a combination of laboratory tests and clinical findings, healthcare providers can improve the diagnosis, treatment, and management of SLE, as suggested by recent studies 1. Ultimately, the goal of SLE management is to reduce morbidity, mortality, and improve quality of life for patients with this complex and multifaceted disease, as emphasized by recent expert recommendations 1.

From the Research

Laboratory Tests for SLE

• The assessment of SLE involves accurate physical and laboratory diagnosis, monitoring of disease activity, and recording of accumulated organ morbidity 2.
• Laboratory tests for SLE include anti-Sm antibodies, anti-dsDNA antibodies, and complement (C3) assays 3.
• Anti-Sm antibodies are essential for diagnosis of SLE, especially in anti-dsDNA-negative patients, and are associated with age, number of ACR criteria, and disease activity 3.
• Antinuclear antibodies (ANAs) are a hallmark of SLE, and levels of anti-DNA antibodies can fluctuate widely, whereas anti-RBP antibodies tend to be stable 4.
• Repeat testing of anti-DNA antibodies is common, as levels can reflect disease activity, whereas a single anti-RBP antibody determination is thought to suffice for clinical purposes 4.

Diagnostic Tools and Approaches

• The classification criteria for SLE include standard and emerging diagnostic tools, such as autoantibody tests and complement activation 5.
• Autoantibody tests, including ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, and anti-La, are used to diagnose and monitor SLE 6.
• The behavior of autoantibodies over time can vary, with some antibodies, such as ANA, remaining positive, while others, such as complement, may have less agreement due to response to treatment 6.
• Emerging diagnostic approaches include the use of novel therapeutics, nonpharmacologic interventions, and comorbidity management 5.

Clinical Significance of Autoantibodies

• Anti-Sm antibodies are associated with lupus nephritis and can be used to monitor disease activity in patients with active lupus nephritis 3.
• Anti-dsDNA antibodies are associated with disease activity and can be used to monitor treatment response 3, 4.
• ANAs are a sensitive marker for SLE, but may not be specific, and can be negative in some patients with SLE 4, 6.
• The clinical significance of autoantibodies in SLE is complex and depends on the specific antibody and the clinical context 3, 4, 6.