Laboratory Work to Investigate for Lupus
When investigating for systemic lupus erythematosus (SLE), order a comprehensive autoantibody panel at baseline including ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid antibodies, along with complement levels (C3, C4), complete blood count, serum creatinine, urinalysis with protein/creatinine ratio, ESR, CRP, and serum albumin. 1
Core Autoantibody Panel
The European League Against Rheumatism (EULAR) provides clear guidance on baseline immunological testing:
ANA (antinuclear antibody): This is the primary screening test for SLE 2. An ANA titer ≥1:40 with characteristic multiorgan involvement supports the diagnosis, though testing should only be performed in patients with unexplained involvement of two or more organ systems to avoid false positives in low-prevalence populations 2
Anti-dsDNA antibodies: These correlate with disease activity and active renal disease, though elevated levels alone without clinical activity do not warrant treatment 1. Changes in anti-dsDNA titres can be useful for monitoring disease progression 1
Anti-Sm antibodies: Part of the baseline panel with prognostic value 1
Anti-Ro (SSA) and anti-La (SSB) antibodies: These have prognostic value and are associated with neonatal lupus risk, making them essential before pregnancy 1
Anti-RNP antibodies: May provide prognostic information 1
Anti-phospholipid antibodies: Associated with thrombotic manifestations, damage development, and pregnancy complications 1. Should be re-evaluated before pregnancy, surgery, transplant, estrogen-containing treatments, or with new neurological/vascular events 1
Complement Levels
- C3 and C4: Baseline measurement is essential 1. Low complement levels (particularly C3) predict flares with an odds ratio of 2 3. Complement levels sometimes correlate with active disease, especially in renal involvement 1
Routine Laboratory Tests
Hematologic Assessment
- Complete blood count (CBC): Essential for detecting cytopenias 1
Inflammatory Markers
ESR (erythrocyte sedimentation rate): Recommended at baseline and for monitoring 1
CRP (C-reactive protein): While controversial in SLE, it has important clinical utility 1. A critical caveat: patients with SLE rarely have elevated CRP during disease flares 1. However, significantly elevated CRP (>5-6 mg/dL) suggests superimposed infection with 80-84% specificity, particularly when >50 mg/L 1, 4. This distinction is crucial for clinical decision-making between treating infection versus lupus flare 4
Renal Function Assessment
Serum creatinine (or eGFR): Provides prognostic information about renal involvement 1
Serum albumin: Low levels indicate renal involvement and poor prognosis 1
Urinalysis with urine protein/creatinine ratio: Essential for detecting and monitoring nephritis 1. Patients with persistently abnormal urinalysis or elevated creatinine should have urine microscopy and be considered for renal biopsy 1
Clinical Context and Pitfalls
Common pitfall: Ordering ANA in patients without multiorgan involvement leads to false positives due to low disease prevalence in primary care 2. Only order when at least two organ systems are involved with unexplained symptoms 2.
Important nuance: If ANA is positive at 1:40 with characteristic multisystem involvement, the diagnosis can be established without additional testing 2. However, if clinical criteria are incomplete, proceed with anti-dsDNA and anti-Sm testing 2.
Monitoring consideration: In established SLE, anti-dsDNA and C3/C4 levels predict flares in asymptomatic patients (OR=3 for high dsDNA, OR=2 for low C3) 3, making them valuable for surveillance even without active symptoms.
Infection versus flare: The hsCRP threshold of >5-6 mg/dL distinguishes infection from lupus flare with high specificity, while ESR elevates in both conditions and cannot differentiate 4. This is clinically critical when deciding between immunosuppression and antimicrobial therapy.