Antibodies in Paraneoplastic Myasthenia Gravis
In paraneoplastic myasthenia gravis, the primary antibodies found are anti-acetylcholine receptor (AChR) antibodies, along with antibodies against titin and ryanodine receptor (RyR). 1
Primary Antibodies in Paraneoplastic Myasthenia Gravis
Anti-AChR Antibodies
- Present in approximately 86% of myasthenia gravis patients 2
- Primarily IgG1 subclass antibodies that can activate complement 3
- These antibodies target the acetylcholine receptors at the neuromuscular junction
- Can be detected through:
- Radioimmunoprecipitation assay (standard diagnostic test)
- Cell-based assays with clustered AChRs (for detecting low-affinity antibodies in "seronegative" cases) 3
Striational Antibodies
- Anti-titin antibodies - high prevalence in paraneoplastic MG 1
- Anti-ryanodine receptor (RyR) antibodies - high prevalence in paraneoplastic MG 1
- These antibodies are important predictors of clinical outcome in paraneoplastic MG
Clinical Correlation with Antibody Profile
Paraneoplastic MG shares a similar immunological profile with late-onset MG (age ≥50 years), characterized by:
- High prevalence of anti-titin antibodies
- High prevalence of anti-RyR antibodies
- This immunological profile is the most important predictor of clinical outcome 1
The presence of these antibodies correlates with:
- Distinctive non-limb symptom profile at disease onset
- Bulbar, ocular, neck, and respiratory symptoms predominate 1
- More severe disease course compared to non-paraneoplastic MG
Association with Thymoma
- Paraneoplastic MG is most commonly associated with thymoma 1
- In patients with thymoma and specific genetic makeup, the paraneoplastic immune response develops in thymic remnant or peripheral lymphatic tissue
- Rarely, anti-Hu antibodies may also be present in thymoma-associated MG, which can lead to additional paraneoplastic syndromes including autonomic neuropathy 4
Diagnostic Considerations
When evaluating for paraneoplastic MG:
- Test for anti-AChR antibodies (standard radioimmunoprecipitation assay)
- Consider testing for anti-titin and anti-RyR antibodies, especially in older patients
- If standard testing is negative but clinical suspicion remains high, consider cell-based assays that can detect low-affinity AChR antibodies 3
- Monitor antibody levels as changes in anti-AChR antibody levels correlate with clinical improvement 5
Clinical Implications
The antibody profile in paraneoplastic MG has important treatment implications:
- Surgical removal of the thymoma is essential
- Pre-thymectomy plasmapheresis or IV immunoglobulin should be considered to minimize post-thymectomy MG exacerbation risk
- Tacrolimus may be particularly effective in RyR antibody-positive patients 1
- Regular monitoring of anti-AChR antibody levels may help assess treatment response 5
It's important to note that the severity of paraneoplastic MG is linked to the patient's immunological profile rather than the presence of thymoma itself 1.