Most Specific Serum Test for MOG
The most specific serum test for MOG is a cell-based assay (CBA) using full-length human MOG as the target antigen with Fc-specific (or IgG1-specific) secondary antibodies, which represents the current gold standard for MOG-IgG detection. 1
Recommended Assay Methodology
Cell-based assays are the only recommended approach for MOG antibody testing, with specific technical requirements: 1
- Must employ full-length human MOG as the target antigen (not peptides or denatured protein)
- Fc-specific or IgG1-specific secondary antibodies are highly recommended to avoid cross-reactivity with IgM and IgA antibodies
- Available formats include indirect fluorescence test (IFT) or fluorescence-activated cell sorting (FACS)
Obsolete/Not Recommended Tests
The following assays are insufficiently specific and should NOT be used: 1
- Peptide-based ELISA
- Western blot
- Immunohistochemistry (less sensitive than CBAs, limited specificity data)
Specimen Selection
Serum is the specimen of choice for MOG-IgG testing: 1
- MOG-IgG is produced mostly extrathecally, resulting in higher serum titers than CSF
- Shipment at 4°C or on dry ice is advisable if samples don't arrive within 1-2 days
- CSF testing is not usually required and has very low sensitivity (2.63%) and positive predictive value (1.97%) when serum is negative 2
When CSF May Be Considered
CSF testing is potentially helpful only in rare, selected cases with strong background due to co-existing high-titer non-MOG serum antibodies 1. However, CSF-restricted MOG-IgG should be interpreted with extreme caution as most such cases have alternate diagnoses (multiple sclerosis, CNS vasculitis) 2.
Immunoglobulin Class Testing
Test for MOG-IgG only: 1
- MOG-IgG testing is recommended
- MOG-IgM and MOG-IgA testing is currently NOT recommended - clinical relevance of isolated MOG-IgM or -IgA results is unknown
- Testing for IgM requires removal of total IgG to avoid false results
Assay Performance Considerations
Live cell-based assays with IgG1-specific antibodies show the highest specificity (100%) but may miss some MOG-IgG2 reactivities: 3
- Live-CBA with anti-heavy-and-light chain: 89.1% sensitivity, 93.3% specificity
- Live-CBA for IgG1: 74.6% sensitivity, 100% specificity
- Live-CBA with anti-Fcγ: 92.3% sensitivity, 97.0% specificity
- Fixed-CBA with anti-Fcγ: 87.2% sensitivity, 97.0% specificity (risk of false-negatives)
Critical Interpretation Points
Antibody titers matter significantly for diagnostic accuracy: 1, 3
- High-titer MOG-IgG (≥1:640) has greater diagnostic significance
- Low-titer results (1:160-1:320) require careful clinical correlation
- All positive results must be interpreted in clinical context - false positives occur, especially with indiscriminate testing of large unselected populations 4, 5
Timing Considerations
MOG-IgG concentrations are disease-activity dependent: 1
- Higher concentrations during acute attacks than remission
- Lower concentrations while on immunosuppression
- May transiently vanish after plasma exchange
- If negative but MOGAD suspected: retest during acute attacks, treatment-free intervals, or 1-3 months after plasma exchange/IVIG
Common Pitfalls to Avoid
Red flags requiring confirmatory testing: 1
- If clinical presentation is atypical for MOGAD, retest the positive serum sample
- Use a second (or third) methodologically different cell-based assay if results are discrepant
- IVIG pretreatment may cause false-negative or false-positive results 1
- Progressive disease course is very atypical for MOGAD and should prompt reconsideration 6
Documentation requirements: All results should document immunoglobulin class detected, assay type, antigenic substrate, biomaterial used, titer/concentration, assay-specific cut-offs, and performing laboratory 1