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Updated: Jan 18, 2026
A Simple Cell-based Immunofluorescence Assay to Detect Autoantibody Against the N-Methyl-D-Aspartate NMDA Receptor in Blood
Published on: January 9, 2018
Testing for N-methyl-d-aspartate Receptor Autoantibodies in Clinical Practice
John Brooks1, Melanie L Yarbrough2, Robert C Bucelli3
1Department of Medicine, Division of Neurology, University of Ottawa, Ottawa, Ontario, Canada.
Background:
The diagnosis of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis relies on the detection of NMDAR IgG autoantibodies in the serum or cerebrospinal fluid (CSF) of symptomatic patients. Commercial kits are available that allow NMDAR IgG autoantibodies to be measured in local laboratories. However, the performance of these tests outside of reference laboratories is unknown.
Objectives:
To report an unexpectedly low rate of NMDAR autoantibody detection in serum from patients with anti-NMDAR encephalitis tested using a commercially available diagnostic kit in an exemplar clinical laboratory.
Methods:
Paired CSF and serum samples from seven patients with definite anti-NMDAR encephalitis were tested for NMDAR IgG autoantibodies using commercially available cell-based assays run according to manufacturer's recommendations. Rates of autoantibody detection in serum tested at our center were compared with those derived from systematic review and meta-analyses incorporating studies published during or before March 2019.
Results:
NMDAR IgG autoantibodies were detected in the CSF of all patients tested at our clinical laboratory but not in paired serum samples. Rates of the detection were lower than those previously reported. A similar association was recognized through meta-analyses, with lower odds of NMDAR IgG autoantibody detection associated with serum testing performed in nonreference laboratories.
Conclusions:
Commercial kits may yield lower-than-expected rates of NMDAR IgG autoantibody detection in serum when run in exemplar clinical (nonreference) laboratories. Additional studies are needed to decipher the factors that contribute to lower-than-expected rates of serum positivity. CSF testing is recommended in patients with suspected anti-NMDAR encephalitis.
Insights
Commercial diagnostic kits may underdetect anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis autoantibodies in patient serum. Cerebrospinal fluid (CSF) testing is recommended for suspected NMDAR encephalitis due to lower serum detection rates in non-reference labs.
Area of Science:
- Neuroimmunology
- Diagnostic test performance
- Autoimmune encephalitis
Background:
- Diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis relies on detecting NMDAR IgG autoantibodies in serum or CSF.
- Commercial kits are available for NMDAR IgG autoantibody testing in local laboratories.
- The performance of these commercial kits in non-reference laboratories is not well-established.
Purpose of the Study:
- To report an unexpectedly low rate of NMDAR autoantibody detection in serum samples.
- To compare commercial kit performance in an exemplar clinical laboratory versus reference laboratory data.
Main Methods:
- Paired CSF and serum samples from seven patients with confirmed anti-NMDAR encephalitis were analyzed.
- Commercially available cell-based assays were used for NMDAR IgG autoantibody detection.
- Serum detection rates were compared to systematic review and meta-analysis data from March 2019.
Main Results:
- NMDAR IgG autoantibodies were detected in CSF of all tested patients.
- No NMDAR IgG autoantibodies were detected in paired serum samples.
- Meta-analyses indicated lower odds of serum autoantibody detection in non-reference laboratories.
Conclusions:
- Commercial kits may exhibit lower-than-expected serum NMDAR IgG autoantibody detection rates in non-reference labs.
- Further research is needed to identify factors contributing to reduced serum positivity rates.
- Cerebrospinal fluid (CSF) testing is recommended for suspected anti-NMDAR encephalitis.
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