title: Identification of coronin-1a as a novel antibody target for clinically isolated syndrome and multiple sclerosis.
abstract: Recently, we identified the mimotope UH-CIS6 as a novel candidate antibody target for clinically isolated syndrome (CIS) and relapsing-remitting (RR) multiple sclerosis (MS). The purpose of this study was to further validate UH-CIS6 as an antibody target for CIS and MS and to identify the in vivo antibody target of UH-CIS6. First, a UH-CIS6 peptide ELISA was optimized. Next, we investigated the antibody response toward UH-CIS6 in cerebrospinal fluid (CSF) from patients with CIS (n = 20), MS (n = 43) and other neurological diseases (n = 42). Immunoprecipitation of anti-UH-CIS6 antibodies on a normal human brain lysate was performed to identify the in vivo antibody target of UH-CIS6. The cellular expression of an in vivo candidate target was investigated by immunohistochemistry using MS brain tissue sections. Antibody reactivity toward UH-CIS6 was detected in a significantly increased proportion of CSF samples from CIS and RR-MS patients as compared with neurological controls (p = 0.046). We identified and confirmed coronin-1a as the in vivo antibody target for UH-CIS6. Furthermore, coronin-1a was expressed by T cells and macrophages in an active MS lesion. Together, these results demonstrate that coronin-1a is a novel antibody target for CIS and MS.
authors.affiliation: Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium.
authors.forename: Myrthe
authors.initials: M
authors.lastname: Rouwette
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Noben
authors.forename: Jack
authors.initials: J
authors.lastname: Van Horssen
authors.forename: Bart
authors.initials: B
authors.lastname: Van Wijmeersch
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jongen
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
authors.forename: Piet
authors.initials: P
authors.lastname: Stinissen
authors.forename: Veerle
authors.initials: V
authors.lastname: Somers
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000134:cerebrospinal fluid / Q000276:immunology / Q000302:isolation & purification; D001667:Binding, Competitive / Q000276:immunology; D001921:Brain / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid / Q000276:immunology / Q000302:isolation & purification; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D008840:Microfilament Proteins; C072061:coronin proteins
keywords: antibody target; clinically isolated syndrome; coronin-1a; multiple sclerosis