Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Probst, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Komorowski, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED de Graaff, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED van Coevorden-Hameete, Marleen UNSPECIFIED UNSPECIFIED UNSPECIFIED Rogemond, Veronique UNSPECIFIED orcid.org/0000-0003-2098-920X UNSPECIFIED Honnorat, Jerome UNSPECIFIED UNSPECIFIED UNSPECIFIED Sabeter, Lidia UNSPECIFIED UNSPECIFIED UNSPECIFIED Graus, Francesc UNSPECIFIED orcid.org/0000-0002-8924-8322 UNSPECIFIED Jarius, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Voltz, Raymond UNSPECIFIED UNSPECIFIED UNSPECIFIED Wildemann, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Franciotta, Diego UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloecker, Inga M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Smitt, Peter A. E. Sillevis UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language FACTOR-RELATED RECEPTOR; TR ANTIBODIES; DISEASE; PROTEIN Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40441