Blood Tests for Autoimmune Encephalitis Panel
Order serum neuronal autoantibodies (NAAs) panel along with targeted blood tests to exclude competing etiologies, with samples collected before any immunotherapy administration. 1
Core Autoimmune Testing
Serum neuronal autoantibodies panel is essential and should include testing for: 2
- Anti-NMDAR (N-methyl-D-aspartate receptor)
- Anti-LGI1 (Leucine-rich glioma inactivated)
- Anti-CASPR2 (Contactin-associated protein-like 2)
- Anti-VGKC (voltage-gated potassium channel complex)
- Anti-AMPAR (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor)
- Anti-GABA-B receptor
- Anti-GFAP (glial fibrillary acidic protein)
- Onconeuronal antibodies (paraneoplastic panel)
Critical Timing Consideration
Collect blood samples before administering intravenous immunoglobulins or plasmapheresis to avoid false positive or false negative results. 1
Essential Exclusionary Blood Tests
The following tests exclude competing etiologies and should be ordered based on clinical presentation: 1
Infectious workup:
- HIV testing
- Treponemal antibodies (syphilis)
Autoimmune/inflammatory markers:
- Antinuclear antibodies (ANA)
- Extractable nuclear antigen (ENA) antibodies
- Antiphospholipid antibodies
- Lupus anticoagulant
- Inflammatory markers (ESR, CRP)
Metabolic/nutritional:
- Vitamin B1 (thiamine) level
- Vitamin B12 level
- Ammonia level
- Metabolic panel (comprehensive)
- Hormonal panels when clinically indicated
Thyroid function:
- Antithyroid antibodies (anti-TPO, anti-thyroglobulin)
- TSH and free T4
Other essential tests:
- Toxicology screen
- Immunoglobulin levels (IgG, IgA, IgM)
- Sodium level (critical for monitoring, as hyponatremia is common with LGI-1 antibody encephalitis) 1
Important Testing Nuances
Serum vs CSF Sensitivity
Testing both serum AND CSF is recommended because sensitivity varies by antibody type: 1
- Serum is more sensitive for: LGI1, CASPR2, onconeuronal antibodies, and AQP4 antibodies
- CSF is more sensitive for: NMDAR and GFAP antibodies
Commercial Assay Limitations
Commercial immunofluorescence assays miss 9-18% of true positive cases, particularly for GABA-B receptor (39% false negative rate), LGI1 (17%), and AMPAR (11%) antibodies in CSF. 3 If clinical suspicion remains high despite negative commercial testing, request comprehensive antibody studies using both cell-based and tissue-based assays. 4, 5
MRI-Guided Testing Strategy
Tailor additional blood tests based on MRI anatomical patterns when present, though comprehensive testing is warranted even with negative MRI since routine studies may be normal in some AE patients. 1
Common Pitfalls to Avoid
- Do not delay antibody testing if CSF shows normal cell counts—AE can present with normal routine CSF studies 1
- Do not rely solely on commercial assays—false negatives occur frequently, especially in CSF samples (29% vs 10% in serum) 3
- Do not skip serum testing even when CSF is available—some antibodies are better detected in serum 1
- Do not forget cancer screening—order CT chest/abdomen/pelvis as paraneoplastic and non-paraneoplastic presentations are clinically indistinguishable 6