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Testing for N-methyl-d-aspartate Receptor Autoantibodies in Clinical Practice

  • John Brooks (a1), Melanie L. Yarbrough (a2), Robert C. Bucelli (a3) and Gregory S. Day (a3)

Abstract:

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.

Effectuer en pratique clinique des tests visant à mesurer les anticorps anti-récepteurs NMDA. Contexte: Le diagnostic de l’encéphalite limbique avec anticorps anti-récepteurs NMDA repose sur la détection d’autoanticorps de classe IgG dans le sérum ou le liquide céphalo-rachidien des patients symptomatiques. Il existe certes des trousses commerciales qui permettent de mesurer ces autoanticorps dans des laboratoires locaux. Cependant, l’efficacité de ces tests en dehors de laboratoires homologués demeure inconnue. Objectif: Signaler un taux d’autoanticorps étonnamment faible dans le sérum de patients atteints d’encéphalite limbique avec anticorps anti-récepteurs NMDA, et ce, au moyen d’une trousse diagnostique commerciale utilisée dans un laboratoire clinique de haut niveau. Méthodes: En suivant les recommandations d’un fabricant, nous avons testé les échantillons appariés de liquide céphalo-rachidien et de sérum de sept patients atteints d’encéphalite limbique avec anticorps anti-récepteurs NMDA. À l’aide d’un bio-essai cellulaire, l’objectif était alors de détecter dans notre centre des autoanticorps de classe IgG et de comparer nos résultats à ceux obtenus à la suite d’une synthèse systématique et de méta-analyses incluant des études publiées au cours du mois de mars 2019 ou avant cette période. Résultats:Des autoanticorps de classe IgG en lien avec des anticorps anti-récepteurs NMDA ont été détectés dans le liquide céphalo-rachidien de tous les patients qui ont fait l’objet d’un test dans notre laboratoire clinique mais non pas dans les échantillons de sérum appariés. Les taux de détection se sont révélés plus faibles que ceux signalés précédemment. Nous avons observé une association similaire lors de méta-analyses, la probabilité de détecter des autoanticorps de classe IgG en lien avec des anticorps anti-récepteurs NMDA étant plus faible lorsqu’associée à des tests de sérum réalisés dans des laboratoires non homologués. Conclusions: Il est donc possible que les trousses commerciales ne débouchent sur des taux de détection d’autoanticorps de classe IgG plus faibles dans les sérums lorsqu’elles sont utilisées dans des laboratoires cliniques de haut niveau qui ne sont pas homologués. Des études complémentaires sont nécessaires pour mieux comprendre les facteurs qui contribuent à ces taux de positivité sérique plus bas que prévus. Enfin, des tests du liquide céphalo-rachidien sont recommandés chez des patients dont on soupçonne qu’ils sont atteints d’encéphalite limbique avec anticorps anti-récepteurs NMDA.

Copyright

Corresponding author

Correspondence to: Gregory S. Day, Department of Neurology, Washington University School of Medicine, Knight Alzheimer Disease Research Center, 4488 Forest Park Ave, St. Louis, MO 63108, USA. Email: gday@wustl.edu

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Testing for N-methyl-d-aspartate Receptor Autoantibodies in Clinical Practice

  • John Brooks (a1), Melanie L. Yarbrough (a2), Robert C. Bucelli (a3) and Gregory S. Day (a3)

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