What is ANA and How to Interpret It
Definition and Modern Understanding
ANA (Antinuclear Antibody) is a historical term that now encompasses autoantibodies directed against various cellular compartments—not just the nucleus—including nuclear constituents, cytoplasmic organelles, mitotic apparatus, and cell membranes. 1 The term is technically outdated, as these antibodies may target both nuclear and non-nuclear elements, and international experts now prefer the term "anticellular antibodies." 1
Clinical Significance in Transverse Myelitis
In an older adult patient with transverse myelitis, a positive ANA warrants immediate and aggressive investigation for systemic lupus erythematosus (SLE), as this combination can be life-threatening without prompt treatment. 2
Critical Disease Associations
- All patients with lupus transverse myelopathy have positive ANA, making this a mandatory screening test when transverse myelitis is diagnosed. 2
- Longitudinally extensive transverse myelitis in older adults with positive ANA strongly suggests SLE, particularly when anti-aquaporin 4 antibodies are also present. 3
- Recurrent transverse myelitis with positive ANA and anti-DNA antibodies indicates an autoimmune etiology requiring immunosuppressive therapy. 4
Interpretation Framework
Titer-Based Clinical Significance
- At 1:160 or higher: 86.2% specificity and 95.8% sensitivity for systemic autoimmune diseases—this titer demands comprehensive workup regardless of symptoms. 1, 5
- At 1:80: Only 74.7% specificity, with 13.3% of healthy individuals testing positive—interpret with extreme caution. 1, 5
- At 1:40: Positive in 31.7% of healthy individuals, considered "low antibody level" with minimal clinical significance without supporting symptoms. 6, 5
Pattern Recognition and Next Steps
- Homogeneous pattern: Order anti-dsDNA antibodies immediately, as this pattern strongly suggests SLE and correlates with the transverse myelitis presentation. 6, 5
- Fine speckled pattern: Order anti-SSA/Ro, anti-SSB/La, and anti-Topoisomerase-1, associated with SLE, Sjögren's syndrome, and systemic sclerosis. 6
- Coarse speckled pattern: Order anti-U1-SnRNP and anti-Sm antibodies, seen in mixed connective tissue disease and SLE. 6
Mandatory Follow-Up Testing Algorithm
Immediate Testing (Within 24-48 Hours for Transverse Myelitis)
- Anti-dsDNA antibodies using Crithidia luciliae immunofluorescence test (CLIFT) for high specificity, followed by solid phase assay for sensitivity. 1, 6
- Anti-aquaporin 4 antibodies are paramount in transverse myelitis to distinguish neuromyelitis optica spectrum disorder from lupus myelitis. 3
- Complete blood count to assess for cytopenias characteristic of autoimmune disease. 6
- Comprehensive metabolic panel for renal and hepatic function. 6
- Urinalysis for proteinuria and hematuria suggesting lupus nephritis. 6
- Complement levels (C3, C4) as low levels correlate with active SLE. 6
Secondary Testing Based on Initial Results
- Extractable nuclear antigen (ENA) panel including anti-Sm, anti-RNP, anti-SSA/Ro, anti-SSB/La, anti-Scl-70, and anti-Jo-1. 1, 5
- Anti-phospholipid antibodies, as these were present in the reported case of lupus transverse myelitis. 3
- Anti-C1q antibodies if lupus nephritis is suspected (present in almost 100% of active lupus nephritis). 6
Critical Management Principles for Transverse Myelitis
Time-Sensitive Treatment Considerations
- Early diagnosis and treatment with high-dose IV pulse steroids within 1 week of transverse myelitis onset dramatically improves outcomes, with delayed treatment resulting in death or permanent wheelchair dependence. 2
- Four of seven patients with lupus transverse myelopathy died when diagnosis and treatment were delayed, while only the two patients treated within 1 week achieved full ambulation. 2
Common Pitfalls to Avoid
- Never use ANA for disease monitoring—it is intended solely for diagnostic purposes, and repeating ANA after diagnosis is neither appropriate nor cost-effective. 1, 5
- Do not dismiss negative ANA with high clinical suspicion, as some specific autoantibodies (anti-Jo-1, anti-ribosomal P, anti-SSA/Ro) may be present in ANA-negative patients. 1, 6
- Indirect immunofluorescence assay (IIFA) on HEp-2 cells remains the gold standard—alternative automated methods may produce false negatives, and IIFA must be performed if clinical suspicion is high despite negative automated testing. 1
- In elderly patients, specificity and positive predictive value are lower than in younger patients, requiring more cautious interpretation. 7
Age-Specific Considerations
In older adults (≥65 years), positive ANA results are more common but have lower specificity for autoimmune disease. 7 However, in the context of transverse myelitis, age should not delay aggressive investigation, as lupus transverse myelopathy has been documented in an 80-year-old patient with excellent response to appropriate treatment. 3
Reporting Requirements
Laboratories must report both the titer (highest dilution showing reactivity) and the specific immunofluorescence pattern, as both are clinically significant for determining follow-up testing and disease associations. 1, 6 The testing method (IIFA versus automated platforms) must also be specified, as different methods have different performance characteristics. 1, 5