Performance of a Commercial Tissue-Based Assay for Neuronal Surface Antibody Detection
Claudia Papi1, Chiara Milano2, Lionel Arlettaz3, Pietro Businaro4, Laura Naranjo5, Raquel Ruiz García5, Matteo Gastaldi4, Raffaele Iorio6, Lidia Sabater7, Josep Dalmau7, Francesc Graus8, Marianna Spatola7
1Neuroimmunology Program, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomédiques August Pi i Sunyer (FRCB-IDIBAPS), University of Barcelona, Spain; Caixa Research Institute (CRI), Barcelona, Spain; Department of Neuroscience, Catholic University of the Sacred Heart, Rome, Italy, 2Neuroimmunology Program, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomédiques August Pi i Sunyer (FRCB-IDIBAPS), University of Barcelona, Spain; Caixa Research Institute (CRI), Barcelona, Spain; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, 3Service d’Immunologie et Allergologie, Institut Central des Hôpitaux, Hôpital du Valais, Sion, Switzerland, 4University of Pavia and Neuroimmunology research unit, IRCCS Mondino Foundation, Pavia, Italy, 5Immunology Service, Biomedical Diagnostic Center, Hospital Clínic, Barcelona, Spain, 6Department of Neuroscience, Catholic University of the Sacred Heart, Rome, Italy, 7Neuroimmunology Program, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomédiques August Pi i Sunyer (FRCB-IDIBAPS), University of Barcelona, Spain; Caixa Research Institute (CRI), Barcelona, Spain, 8Neuroimmunology Program, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomédiques August Pi i Sunyer (FRCB-IDIBAPS), University of Barcelona, Spain
Objective:
To assess the performance of a commercial tissue-based assay (TBA) in detecting neuronal surface antibodies (NSAbs).
Background:
Detection of NSAbs is critical to diagnose autoimmune encephalitis (AE). The recommended diagnostic strategy includes TBAs and cell-based assays (CBAs). This two-step approach is mainly used in reference/specialized centers employing in-house TBAs. However, many clinical laboratories rely on commercial TBAs, the accuracy of which has not been properly determined.
Design/Methods:
We selected 92 CSF and 99 sera from patients with AE and NSAbs (20 samples with each of these Abs: AMPAR, GABAAR, GABABR, IgLON5, LGI1, NMDAR, Caspr2; 19 mGluR5, 17 DPPX, 15 mGluR1), and 50 CSF and 50 sera from individuals without NSAbs to assess the performance of a commercial TBA (Euroimmun). NSAbs were confirmed using highly sensitive and specific in-house TBA (Dalmau et al., Physiol Rev 2017) and CBA. Slides were assessed as “positive” or “negative” by two experienced investigators (FG,JD) and, if discordant, an interrater discussion was performed.
Results:
The two raters were concordant in classifying 94% (133/142) of CSF and 88% (131/149) of sera. Among CSF samples, 75% (106/142) were correctly identified, while 19% (27/142) were misclassified: 13 false positive (FP), 14 false negative (FN). As for sera, 66% (98/149) were correctly identified and 22% (33/149) misclassified: 11 FP, 22 FN. The worst performance was observed for NMDAR, GABAAR, and mGluR5 Abs (not identified in 5/10, 6/10, 5/9 sera and in 4/10, 5/10, 5/10 CSF, respectively). The overall sensitivity of the commercial TBA was 83,7% for CSF and 75,8% for serum, while the specificity was 72,3% for CSF and 72,5% for serum.
Conclusions:
The diagnostic performance of a TBA (Euroimmun) for NSAbs is suboptimal. NMDAR antibodies, one of the most frequent NSAbs, can be missed in 50% of patients. Our findings suggest that this TBA should not be used as initial screening for NSAbs.
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