What is the AVISE laboratory test?

AVISE Laboratory Test

AVISE is a proprietary multi-biomarker laboratory test panel developed to aid in the diagnosis and management of systemic lupus erythematosus (SLE) and other autoimmune rheumatic diseases by measuring multiple autoantibodies and cell-bound complement activation products simultaneously.

What AVISE Measures

The AVISE test is not a single assay but rather a comprehensive panel that typically includes:

• Traditional autoantibody testing including ANA by immunofluorescence, anti-dsDNA antibodies, anti-Smith antibodies, and extractable nuclear antigen (ENA) panel (anti-SSA/Ro, anti-SSB/La, anti-RNP, anti-Scl-70, anti-Jo-1), which are the standard disease-specific antibodies recommended by the American College of Rheumatology for evaluating suspected autoimmune disease 1, 2

• Cell-bound complement activation products (CB-CAPs) measuring C4d and C3d bound to erythrocytes and platelets, which represent a novel biomarker approach beyond traditional serologic testing 1

• Additional autoantibodies that may include antiphospholipid antibodies, anti-histone antibodies, and other disease-specific markers depending on the specific AVISE panel ordered 2, 3

Clinical Context and Appropriate Use

AVISE should only be ordered when there is genuine clinical suspicion of systemic autoimmune rheumatic disease based on compatible symptoms and physical findings, not as a screening test in asymptomatic individuals. The test is most appropriately used in the following scenarios:

• Patients with clinical features suggesting SLE (malar rash, photosensitivity, oral ulcers, serositis, arthritis, renal disease, neurologic symptoms, cytopenias) who require comprehensive autoantibody profiling 1, 2

• Patients with positive ANA screening at titers ≥1:160 who need specific autoantibody identification to determine which autoimmune disease is present, as the ANA alone has only 86.2% specificity at this titer 1, 3

• Monitoring disease activity in established SLE, though traditional ANA testing should not be repeated for monitoring—instead, quantitative anti-dsDNA and complement levels (C3, C4) are more appropriate 2, 3

Interpretation Algorithm

When AVISE results return, interpret systematically:

• If anti-dsDNA or anti-Sm positive: Strongly suggests SLE; evaluate for malar rash, photosensitivity, oral ulcers, serositis, renal disease (urinalysis for proteinuria/hematuria), neurologic symptoms, cytopenias (CBC), and check complement levels (C3, C4) which correlate with disease activity 1, 2

• If anti-SSA/Ro positive: Found in 40-60% of primary Sjögren's syndrome and 30-40% of SLE patients, particularly those with photosensitivity, subacute cutaneous lupus, and neonatal lupus risk 1

• If antiphospholipid antibodies positive: Present in 30-40% of SLE patients and may indicate autoimmune inner ear disease in patients with rapidly progressive bilateral sensorineural hearing loss, vestibular symptoms, or tinnitus 4

• If CB-CAPs elevated: May indicate active complement-mediated tissue damage even when traditional serologies are equivocal, though this biomarker's clinical utility is still being established in routine practice 1

Critical Pitfalls to Avoid

• Never diagnose autoimmune disease based solely on positive AVISE results without compatible clinical symptoms, laboratory abnormalities, and appropriate histological findings when indicated, as the specificity of screening tests is insufficient—only 74.7% at 1:80 titer and 86.2% at 1:160 titer 1, 3

• Recognize that 31.7% of healthy individuals test positive for ANA at 1:40 dilution, 13.3% at 1:80, and 5.0% at 1:160, making positive results common in the absence of disease 1, 3

• Approximately 30-40% of SLE patients never develop anti-dsDNA antibodies, and anti-Smith antibodies are present in only a minority, so negative results do not exclude SLE when clinical suspicion is high 2

• Different laboratories use different methods and cutoffs for the same antibodies, which significantly affects result interpretation—always use the same testing method for serial monitoring if disease is diagnosed 2, 3

• Significant inter-method variability exists in anti-dsDNA detection, with different assays detecting different antibody specificities based on the antigenic material used 2

When to Refer to Rheumatology

• Immediate referral is warranted for ANA titer ≥1:160 with any disease-specific autoantibodies (anti-dsDNA, anti-Sm, anti-SSA/Ro, anti-Scl-70, anti-Jo-1) regardless of symptoms, as specific autoantibodies may present years before overt disease manifestation, and early intervention can prevent organ damage 1

• Even asymptomatic patients with ANA ≥1:160 and positive disease-specific antibodies warrant rheumatology consultation to establish baseline assessment and monitoring plan 1

Special Considerations for Autoimmune Inner Ear Disease

If AVISE is being ordered for suspected autoimmune inner ear disease (AIED):

• AIED is characterized by rapidly progressive, often fluctuating, bilateral sensorineural hearing loss over weeks to months, accounting for less than 1% of all hearing impairment cases 5

• Antiphospholipid antibodies show 29% prevalence in AIED patients, with lupus anticoagulant being most frequently detected, followed by anticardiolipin and anti-beta2 glycoprotein 4

• Limited serologic tests including ANA (high level with speckled pattern in 38% of patients) and rheumatoid factor (elevated in 9% of patients) are valuable in establishing AIED diagnosis, though the positive yield of other detailed tests is low 6

• Western blot identification of antibodies to 68-kD inner ear antigen appears promising for identifying immune-mediated inner ear disease, correlating with disease activity and predicting response to corticosteroid treatment 7