Can AChR Antibodies Be False Positive in SLE Patients?
Yes, false positive acetylcholine receptor (AChR) antibody tests can occur in patients with SLE, though this is uncommon, and the clinical context must guide interpretation rather than relying solely on antibody results.
Understanding False Positive AChR Antibodies
The risk of false positive AChR antibody results exists even with the gold standard radioimmunoprecipitation assay (RIPA), which has a specificity of approximately 98.9% in clinical practice 1. This means that approximately 1-2% of positive results may not represent true myasthenia gravis (MG).
Key Factors Associated with False Positivity
Low antibody titers are the strongest predictor of false positivity:
- Titers between 0.5-0.9 nmol/L carry significantly higher risk of false positivity 1
- When titers are ≥1 nmol/L, the positive predictive value increases to 96.6% 1
- Patients with false positive results have median titers of 0.7 nmol/L compared to 6 nmol/L in true MG 1
Patient demographics matter:
- False positive patients tend to be younger (median age 38 vs 65 years in true MG) 1
- Female patients show higher rates of false positivity (74% vs 49.8%) 1
SLE-Specific Considerations
While SLE patients can have positive AChR antibodies, this typically represents one of two scenarios:
True coexistence of SLE and MG - documented cases exist where patients have both conditions with distinct, non-cross-reactive antibody populations 2
False positive results in the context of autoimmune disease - rheumatic diseases are among the documented causes of false positive AChR antibodies 1
Documented False Positivity in Autoimmune Conditions
False positive AChR antibodies have been reported in several autoimmune conditions beyond SLE 3:
- Primary biliary cirrhosis
- Eaton-Lambert syndrome
- Graves' ophthalmopathy
Diagnostic Algorithm for AChR Positivity in SLE Patients
Step 1: Assess the clinical phenotype
- Does the patient have fluctuating weakness, fatigable ptosis, or diplopia consistent with MG? 1
- Are symptoms better explained by SLE manifestations (arthritis, serositis, nephritis)? 1
Step 2: Evaluate the antibody titer
- Titers <1 nmol/L warrant extreme caution and consideration of false positivity 1
- Titers ≥1 nmol/L are more likely to represent true MG 1
Step 3: Consider confirmatory testing
- Repeat testing may show seronegativity in false positive cases (55% become negative vs only 8% in true MG) 1
- Fixed cell-based assay (CBA) can help clarify equivocal cases, as false positives often test negative on CBA 1
- Selective positivity against fetal AChR isoform on CBA suggests false positivity 1
Step 4: Perform electrophysiological testing
- Repetitive nerve stimulation or single-fiber EMG should be performed if clinical suspicion for MG exists 4
- Normal electrophysiology in the context of low-titer AChR antibodies strongly suggests false positivity
Critical Pitfalls to Avoid
Do not diagnose MG based solely on positive AChR antibodies in SLE patients, especially with:
- Low titers (0.5-0.9 nmol/L) 1
- Absence of typical myasthenic symptoms 1
- Clinical features fully explained by SLE 1
Recognize that ELISA methods have lower specificity than RIA:
- RIPA (radioimmunoprecipitation assay) is superior to ELISA for AChR antibody detection 3
- If ELISA was used initially and results are questionable, retest with RIA 3
Avoid inappropriate immunosuppressive treatment:
- Misdiagnosis based on false positive antibodies can lead to unnecessary MG-specific treatments 1
- SLE patients already receive immunosuppression, but MG-specific therapies (pyridostigmine, thymectomy consideration) should not be initiated without clinical confirmation 3
When to Suspect False Positivity
High suspicion for false positive when:
- Young female patient with established SLE 1
- AChR antibody titer <1 nmol/L 1
- No clinical features of MG (no fatigable weakness, normal ocular examination, no bulbar symptoms) 1
- Symptoms fully explained by active SLE 1
Consider true MG coexistence when: