How do you interpret Systemic Lupus Erythematosus (SLE) lab results in a young to middle-aged female patient with a history of joint pain, skin rashes, and kidney problems?

SLE Laboratory Interpretation

Initial Screening: ANA Testing is Mandatory

All patients with suspected SLE must have a positive ANA test as the entry criterion for diagnosis, as this is now a required component of the EULAR/ACR 2019 classification criteria. 1, 2

• If ANA is negative, SLE diagnosis is essentially ruled out unless there is exceptionally high clinical suspicion (e.g., strong renal involvement, cytopenias, or characteristic rash patterns). 1
• ANA testing should be performed using indirect immunofluorescence (IIF) as the reference method. 1

Comprehensive Autoantibody Panel (When ANA is Positive)

Once ANA is positive, immediately order the following autoantibodies to establish the diagnosis and assess organ involvement: 2

Essential Autoantibodies:

• Anti-dsDNA antibodies: Use a double-screening strategy with a solid-phase assay (FEIA, CLIA, or ELISA) first, followed by Crithidia luciliae immunofluorescence test (CLIFT) for confirmation. 1

  • If both tests are positive: Strong evidence for SLE
  • If solid-phase assay is positive but CLIFT is negative: Consider anti-nucleosome testing and antiphospholipid antibodies; repeat testing in 6 months. 1
  • If solid-phase assay is negative but CLIFT is positive (rare): Repeat testing and maintain clinical follow-up. 1

• Anti-Sm antibodies: Highly specific for SLE (though less sensitive). 2, 3

• Anti-Ro (SSA) and Anti-La (SSB): Essential before pregnancy due to neonatal lupus risk; also associated with subacute cutaneous lupus. 2, 4

• Anti-RNP antibodies: Part of the standard panel. 2

• Antiphospholipid antibodies (anticardiolipin, anti-β2GP1, lupus anticoagulant): Present in 30-40% of SLE patients; test using dilute Russell viper venom time (dRVVT) and sensitive aPTT with mixing studies. 1

  • Repeat positive tests after >12 weeks to confirm persistence. 1

Complement Levels and Inflammatory Markers

Low complement levels (C3, C4) strongly support active SLE and correlate with disease activity, particularly in lupus nephritis. 2, 3

• Measure C3 and C4 at baseline and during follow-up. 2
• Hypocomplementemia is more common in younger patients and those with active disease. 5, 6

ESR and CRP pattern: Elevated ESR with normal or minimally elevated CRP is characteristic of SLE (unlike bacterial infections). 7

Hematologic Assessment

Perform complete blood count to identify cytopenias: 2, 3

• Leukopenia (particularly lymphopenia)
• Thrombocytopenia
• Hemolytic anemia (check direct Coombs test if anemia present)

Renal Involvement Screening

All SLE patients require systematic kidney monitoring, as 40% develop lupus nephritis: 1, 3

Initial Assessment:

• Urinalysis with microscopy: Look for proteinuria (dipstick ≥2+), acanthocytes (≥5%), RBC casts, or WBC casts. 1
• Urine protein-to-creatinine ratio (uPCR): Threshold of 500 mg/day warrants further investigation. 1
• Serum creatinine and eGFR: Assess for decreased or decreasing GFR unexplained by other causes. 1

When to Pursue Kidney Biopsy:

• Persistent proteinuria >500 mg/day with abnormal sediment
• Unexplained decline in eGFR
• Clinical suspicion despite "insignificant" proteinuria (severity varies in active nephritis). 1

Biopsy should be classified using ISN/RPS criteria and read by an experienced renal pathologist. 1

Disease Activity Monitoring

For established SLE, monitor anti-dsDNA and complement levels (C3, C4) to assess disease activity and predict flares. 2

• Rising anti-dsDNA with falling complement suggests impending flare, particularly renal.
• However, anti-dsDNA testing is not FDA-approved for disease monitoring, so interpret changes in clinical context. 1

Special Population Considerations

Age-Related Differences:

• Younger patients (<50 years): Higher disease activity scores, more frequent hypocomplementemia, and higher anti-dsDNA positivity. 5, 6
• Older-onset patients (≥55 years): Milder presentation, less frequent hypocomplementemia, lower proportion of Black patients. 5, 6

High-Risk Populations:

• Asian, African/Caribbean, and Hispanic descent: Higher incidence and more severe disease. 1
• Childhood-onset SLE: Higher incidence of lupus nephritis and more severe disease than adult-onset. 1

Pre-Pregnancy and Pregnancy:

• Test anti-Ro and anti-La before pregnancy (neonatal lupus risk). 2
• Re-evaluate antiphospholipid antibodies before pregnancy, surgery, or estrogen-containing treatments. 2

Common Pitfalls to Avoid

• Do not order anti-dsDNA if ANA is negative (except with very high clinical suspicion). 1
• Do not rely on a single positive antiphospholipid antibody test; confirmation at >12 weeks is mandatory. 1
• Do not dismiss low-level proteinuria in the setting of other SLE features; severity varies in active nephritis. 1
• Do not perform generalized screening in asymptomatic populations; false positives are common. 1