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Standardized test for anti-Tr/DNER in patients with paraneoplastic cerebellar degeneration

Objective: To determine sensitivity and specificity of a standardized recombinant cell-based indirect immunofluorescence assay (RC-IFA) for anti-Tr antibodies in comparison to a reference procedure. - Methods: Delta/Notch-like epidermal growth factor-related receptor (DNER) was expressed in HEK293 a...

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Main Authors: Probst, Christian (Author) , Komorowski, Lars (Author) , de Graaff, Esther (Author) , van Coevorden-Hameete, Marleen (Author) , Rogemond, Veronique (Author) , Honnorat, Jerome (Author) , Sabeter, Lidia (Author) , Graus, Francesc (Author) , Jarius, Sven (Author) , Voltz, Raymond (Author) , Wildemann, Brigitte (Author) , Franciotta, Diego (Author) , Blöcker, Inga M. (Author) , Schlumberger, Wolfgang (Author) , Stöcker, Winfried (Author) , Sillevis Smitt, Peter A.E. (Author)
Format: Article (Journal)
Language:English
Published: February 26, 2015
In: Neurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology
Year: 2015, Volume: 2, Issue: 2
ISSN:2332-7812
DOI:10.1212/NXI.0000000000000068
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1212/NXI.0000000000000068
Verlag, lizenzpflichtig, Volltext: http://nn.neurology.org/lookup/doi/10.1212/NXI.0000000000000068
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Author Notes:Christian Probst, PhD, Lars Komorowski, PhD, Esther de Graaff, PhD, Marleen van Coevorden-Hameete, MD, Veronique Rogemond, PhD, Jerome Honnorat, MD, Lidia Sabeter, MD, Francesc Graus, MD, Sven Jarius, MD, Raymond Voltz, MD, Brigitte Wildemann, MD, Diego Franciotta, MD, Inga M. Blöcker, PhD, Wolfgang Schlumberger, PhD, Winfried Stöcker, MD, Peter A.E. Sillevis Smitt, MD
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Summary:Objective: To determine sensitivity and specificity of a standardized recombinant cell-based indirect immunofluorescence assay (RC-IFA) for anti-Tr antibodies in comparison to a reference procedure. - Methods: Delta/Notch-like epidermal growth factor-related receptor (DNER) was expressed in HEK293 and used as a substrate for RC-IFA. HEK293 control cells expressing CDR2/Yo and CDR2L as well as mock-transfected HEK293 cells were used as controls. Serum samples from 38 patients with anti-Tr antibodies (33 with paraneoplastic cerebellar degeneration [PCD] and Hodgkin lymphoma), 66 patients with anti-Tr-negative PCD, 53 patients with Hodgkin lymphoma without neurologic symptoms, 40 patients with rheumatic diseases, and 42 healthy blood donors were tested for anti-DNER reactivity in the RC-IFA. In addition, RC-IFA results were compared to those from a commercial tissue-based IFA using monkey cerebellum. - Results: Using the RC-IFA, anti-DNER was detected in all anti-Tr-positive patients but in none of the controls (sensitivity 100%, 95% confidence interval [CI] 92.8%-100%; specificity 100%, 95% CI 98.7%-100%). In comparison, anti-Tr was not detected in 4 samples with low-titer autoantibodies using the commercial tissue-based assay. Preadsorption of sera with either recombinant full-length DNER or its extracellular domain selectively abolished anti-Tr reactivity. - Conclusion: Anti-Tr antibodies bind to the extracellular domain of DNER and can be detected by RC-IFA using HEK293 cells expressing the recombinant receptor. The new method performs better than a frequently used commercial tissue-based indirect immunofluorescence assay (IFA) in samples with low-titer antibodies.
Item Description:Gesehen am 22.07.2020
Physical Description:Online Resource
ISSN:2332-7812
DOI:10.1212/NXI.0000000000000068

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