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

From the Guidelines

Lupus testing should always begin with a positive antinuclear antibody (ANA) test, followed by more specific antibody tests, including anti-double-stranded DNA (anti-dsDNA), to confirm the diagnosis of systemic lupus erythematosus (SLE) 1. The diagnosis of SLE is a complex process that involves a combination of clinical evaluation, laboratory tests, and medical history.

• The ANA test is the most common initial test, which is positive in about 97% of lupus patients, though it can be positive in other conditions as well.
• If ANA is positive, more specific antibody tests are typically ordered, including anti-dsDNA, anti-Smith (anti-Sm), anti-SSA/Ro, anti-SSB/La, and anti-RNP antibodies.
• Complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein, and complement levels (C3 and C4) are also important to assess organ function and inflammation.
• Urinalysis helps detect kidney involvement.
• No single test can definitively diagnose lupus, so doctors use the American College of Rheumatology classification criteria, which requires meeting at least 4 of 11 clinical and laboratory criteria.
• 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. Key considerations in lupus testing include:
• The use of anti-ENA autoantibodies, such as anti-dsDNA, anti-Sm, anti-SSA/Ro, anti-SSB/La, and anti-RNP, to confirm the diagnosis of SLE 1.
• The importance of clinical suspicion in interpreting laboratory results, particularly in cases where ANA is positive but anti-dsDNA is negative 1.
• The need for regular follow-up testing to monitor disease activity and treatment effectiveness, as lupus symptoms can fluctuate over time 1.

From the Research

Lupus Testing Overview

• Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation and immune-mediated injury to multiple organ systems 2
• The 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria are estimated to be 96.1% sensitive and 93.4% specific for SLE 2
• These classification criteria include both clinical factors and immunologic measures, such as SLE-specific autoantibodies and low complement levels 2

Laboratory Tests for Lupus

• The antinuclear antibody (ANA) test is positive in nearly every case of SLE, but it is not specific for this disease and must be interpreted in the appropriate clinical context 3
• ANA staining patterns and more specific autoantibody testing may be helpful in diagnosis of suspected SLE or ANA-associated disease 3
• Complete blood count (CBC)-derived biomarkers, such as the systemic immune-inflammation index (SII) and the pan-immune-inflammation value (PIV), may play a role in SLE, but their clinical utility is limited 4

Diagnostic Challenges

• Prompt recognition of SLE in hospitalized patients presenting with severe disease is essential to initiate treatment 5
• Diagnostic delays can occur, particularly in patients with hematological manifestations 5
• The SLE Risk Probability Index (SLERPI) can be useful in diagnosing SLE, but a lower threshold may be needed in patients with certain clinical presentations, such as fever or thrombotic events 5

Key Findings

• Higher ANA titers can predict flares of SLE 4
• Improvement of SLE following treatment is associated with the absence of lymphopenia and ANA > 1:640 4
• The SLEDAI-2K significantly correlates with certain laboratory parameters, such as NLR, SII, CRP, lymphocytes, and monocytes, but only on univariable testing 4