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Title: | Antibody profiling identifies novel antigenic targets in spinal cord injury patients | Authors: | PALMERS, Ilse YDENS, Elke PUT, Eric Depreitere, Bart Bongers-Janssen, Helma Pickkers, Peter HENDRIX, Sven SOMERS, Veerle |
Issue Date: | 2016 | Publisher: | BIOMED CENTRAL LTD | Source: | JOURNAL OF NEUROINFLAMMATION, 13, p. 1-11 (Art N° 243) | Abstract: | Background: Recent evidence implicates antibody responses as pivotal damaging factors in spinal cord injury (SCI)-induced neuroinflammation. To date, only a limited number of the antibody targets have been uncovered, and the discovery of novel targets with pathologic and clinical relevance still represents a major challenge. Methods: In this study, we, therefore, applied an unbiased, innovative and powerful strategy, called serological antigen selection (SAS), to fully identify the complex information present within the antibody repertoire of SCI patients. Results: We constructed a high-quality cDNA phage display library derived from human spinal cord tissue to screen for antibody reactivity in pooled plasma samples from traumatic SCI patients (n = 10, identification cohort). By performing SAS, we identified a panel of 19 antigenic targets to which the individual samples of the plasma pool showed antibody reactivity. Sequence analysis to identify the selected antigenic targets uncovered 5 known proteins, to which antibody reactivity has not been associated with SCI before, as well as linear peptides. Immunoreactivity against 9 of the 19 novel identified targets was validated in 41 additional SCI patients and an equal number of age-and gender-matched healthy subjects. Overall, we found elevated antibody levels to at least 1 of the 9 targets in 51 % of our total SCI patient cohort (n = 51) with a specificity of 73 %. By combining 6 of these 9 targets into a panel, an overall reactivity of approximately half of the SCI patients could be maintained while increasing the specificity to 82 %. Conclusions: In conclusion, our innovative high-throughput approach resulted in the identification of previously unexplored antigenic targets with elevated immunoreactivity in more than 50 % of the SCI patients. Characterization of the validated antibody responses and their targets will not only provide new insight into the underlying disease processes of SCI pathology but also significantly contribute to uncovering potential antibody biomarkers for SCI patients. | Notes: | [Palmers, Ilse; Ydens, Elke; Hendrix, Sven; Somers, Veerle] Hasselt Univ, Biomed Res Inst, Martelarenlaan 42, Hasselt, Belgium. [Palmers, Ilse; Ydens, Elke; Hendrix, Sven; Somers, Veerle] Hasselt Univ, Sch Life Sci, Transnat Univ Limburg, Martelarenlaan 42, Hasselt, Belgium. [Put, Eric] Jessa Hosp, Dept Neurosurg, Stadsomvaart 11, Hasselt, Belgium. [Depreitere, Bart] Katholieke Univ Leuven, Div Expt Neurosurg & Neuroanat, Herestr 49, Leuven, Belgium. [Depreitere, Bart] Univ Hosp Leuven, Herestr 49, Leuven, Belgium. [Bongers-Janssen, Helma] Adelante Rehabil, Zandbergsweg 111, Hoensbroek, Netherlands. [Pickkers, Peter] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Intens Care Med, Geert Grootepl Zuid 10, Nijmegen, Netherlands. | Keywords: | antigenic targets; antibody repertoire; serological antigen selection; cDNA phage display library,; spinal cord injury;Antigenic targets; Antibody repertoire; Serological antigen selection; cDNA phage display library; Spinal cord injury | Document URI: | http://hdl.handle.net/1942/22714 | e-ISSN: | 1742-2094 | DOI: | 10.1186/s12974-016-0713-5 | ISI #: | 000384618300001 | Rights: | © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2017 |
Appears in Collections: | Research publications |
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