What laboratory tests are used for the diagnosis and monitoring of systemic lupus erythematosus (SLE)?

Laboratory Tests for Diagnosis and Monitoring of Systemic Lupus Erythematosus (SLE)

For diagnosis and monitoring of SLE, comprehensive autoantibody testing including ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid antibodies, and complement levels (C3, C4) should be performed at baseline, with regular monitoring of specific markers based on disease activity and organ involvement. 1

Initial Diagnostic Laboratory Evaluation

Core Immunological Tests

• Antinuclear antibody (ANA): First-line screening test
• Anti-double-stranded DNA (anti-dsDNA): Highly specific for SLE
• Anti-extractable nuclear antigens:
  • Anti-Ro (SSA)
  • Anti-La (SSB)
  • Anti-RNP
  • Anti-Sm (highly specific for SLE)
• Anti-phospholipid antibodies:
  • Anticardiolipin antibodies
  • Lupus anticoagulant
  • Anti-β2 glycoprotein I
• Complement components: C3 and C4 levels

General Laboratory Tests

• Complete blood count (CBC)
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
• Serum albumin
• Serum creatinine (or eGFR)
• Urinalysis and urine protein/creatinine ratio

Monitoring Algorithm Based on Disease Activity and Organ Involvement

For Patients with Inactive Disease

Monitor every 6-12 months 1:

• Complete blood count
• ESR
• CRP
• Serum albumin
• Serum creatinine (or eGFR)
• Urinalysis and urine protein/creatinine ratio

For Patients with Active Disease

More frequent monitoring (every 1-3 months) with tests tailored to specific organ involvement:

Renal Involvement

• Urine protein/creatinine ratio (or 24h proteinuria)
• Urine microscopy
• C3, C4, anti-dsDNA (every 3 months for first 2-3 years) 1
• Serum creatinine and eGFR

For patients with persistently abnormal urinalysis or raised serum creatinine 1:

1. Obtain urine protein/creatinine ratio
2. Perform urine microscopy
3. Order renal ultrasound
4. Consider referral for kidney biopsy

Hematological Involvement

• Complete blood count with differential
• Reticulocyte count
• Direct Coombs test (if hemolytic anemia suspected)

Neuropsychiatric Involvement

Laboratory testing should accompany focused neurological assessment 1

Re-evaluation of Previously Negative Autoantibodies

Specific clinical scenarios warrant retesting of previously negative autoantibodies 1:

1. Anti-phospholipid antibodies: Retest prior to:

   • Pregnancy
   • Surgery
   • Transplant
   • Use of estrogen-containing treatments
   • New neurological or vascular event

2. Anti-Ro and Anti-La antibodies: Retest before pregnancy

3. Anti-dsDNA/C3/C4: Monitor to assess disease activity/remission

Predictive Value of Laboratory Tests

Anti-C1q antibodies, when combined with C3 and C4 levels, provide the best performance for predicting lupus nephritis flares 2. In patients with normal values of anti-C1q, C3, C4, and anti-dsDNA, active lupus nephritis is unlikely (high negative predictive value) 2.

Important Caveats and Pitfalls

1. Antibody profile variations: Not all SLE patients will have the same antibody profile. Some patients may have negative anti-dsDNA despite active disease.

2. Membranous vs. proliferative lupus nephritis: Anti-C1q antibodies are more reliable in proliferative lupus nephritis than in membranous lupus nephritis, where 46% of flares may occur with normal anti-C1q levels 2.

3. Antiphospholipid antibody interference: In patients with antiphospholipid antibodies, 33% of renal flares may occur with normal anti-C1q levels, reducing its reliability 2.

4. Discoid lupus monitoring: Patients with discoid lesions confined to the head and neck show fewer laboratory abnormalities than those with disseminated lesions. Persistent multiple abnormal laboratory findings may indicate progression to systemic disease 3.

5. Drug-specific monitoring: Additional laboratory tests may be required based on specific medications (e.g., antimalarials, immunosuppressants) 1.