Probst, Christian, Komorowski, Lars, de Graaff, Esther, van Coevorden-Hameete, Marleen, Rogemond, Veronique ORCID: 0000-0003-2098-920X, Honnorat, Jerome, Sabeter, Lidia, Graus, Francesc ORCID: 0000-0002-8924-8322, Jarius, Sven, Voltz, Raymond, Wildemann, Brigitte, Franciotta, Diego, Bloecker, Inga M. and Smitt, Peter A. E. Sillevis (2015). Standardized test for anti-Tr/DNER in patients with paraneoplastic cerebellar degeneration. Neurol.-Neuroimmunol. Neuroinflammation, 2 (2). PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 2332-7812

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Abstract

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. Classification of evidence: This study provides Class II evidence that RC-IFA accurately detects anti-Tr as compared to conventional IFA.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Probst, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Komorowski, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Graaff, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Coevorden-Hameete, MarleenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rogemond, VeroniqueUNSPECIFIEDorcid.org/0000-0003-2098-920XUNSPECIFIED
Honnorat, JeromeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabeter, LidiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Graus, FrancescUNSPECIFIEDorcid.org/0000-0002-8924-8322UNSPECIFIED
Jarius, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voltz, RaymondUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wildemann, BrigitteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franciotta, DiegoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloecker, Inga M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smitt, Peter A. E. SillevisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-404416
DOI: 10.1212/NXI.0000000000000068
Journal or Publication Title: Neurol.-Neuroimmunol. Neuroinflammation
Volume: 2
Number: 2
Date: 2015
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Place of Publication: PHILADELPHIA
ISSN: 2332-7812
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FACTOR-RELATED RECEPTOR; TR ANTIBODIES; DISEASE; PROTEINMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/40441

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