TY - JOUR
T1 - Epitope specificity of anti-synapsin autoantibodies
T2 - Differential targeting of synapsin i domains
AU - Mertens, Robert
AU - Melchert, Sarah
AU - Gitler, Daniel
AU - Schou, Morten Brix
AU - Saether, Sverre Georg
AU - Vaaler, Arne
AU - Piepgras, Johannes
AU - Kochova, Elena
AU - Benfenati, Fabio
AU - Ahnert-Hilger, Gudrun
AU - Ruprecht, Klemens
AU - Höltje, Markus
N1 - Publisher Copyright:
© 2018 Mertens et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Objective To identify the specific domains of the presynaptic protein synapsin targeted by recently described autoantibodies to synapsin. Methods Sera of 20 and CSF of two patients with different psychiatric and neurological disorders previously tested positive for immunoglobulin (Ig)G antibodies to full-length synapsin were screened for IgG against synapsin I domains using HEK293 cells transfected with constructs encoding different domains of rat synapsin Ia. Additionally, IgG subclasses were determined using full-length synapsin Ia. Serum and CSF from one patient were also screened for IgA autoantibodies to synapsin I domains. Sera from nine and CSF from two healthy subjects were analyzed as controls. Results IgG in serum from 12 of 20 IgG synapsin full-length positive patients, but from none of the healthy controls, bound to synapsin domains. Of these 12 sera, six bound to the A domain, five to the D domain, and one to the B- (and possibly A-), D-, and E-domains of synapsin I. IgG antibodies to the D-domain were also detected in one of the CSF samples. Determination of IgG subclasses detected IgG1 in two sera and one CSF, IgG2 in none of the samples, IgG3 in two sera, and IgG4 in eight sera. One patient known to be positive for IgA antibodies to full-length synapsin had IgA antibodies to the D-domain in serum and CSF. Conclusions Anti-synapsin autoantibodies preferentially bind to either the A- or the D-domain of synapsin I.
AB - Objective To identify the specific domains of the presynaptic protein synapsin targeted by recently described autoantibodies to synapsin. Methods Sera of 20 and CSF of two patients with different psychiatric and neurological disorders previously tested positive for immunoglobulin (Ig)G antibodies to full-length synapsin were screened for IgG against synapsin I domains using HEK293 cells transfected with constructs encoding different domains of rat synapsin Ia. Additionally, IgG subclasses were determined using full-length synapsin Ia. Serum and CSF from one patient were also screened for IgA autoantibodies to synapsin I domains. Sera from nine and CSF from two healthy subjects were analyzed as controls. Results IgG in serum from 12 of 20 IgG synapsin full-length positive patients, but from none of the healthy controls, bound to synapsin domains. Of these 12 sera, six bound to the A domain, five to the D domain, and one to the B- (and possibly A-), D-, and E-domains of synapsin I. IgG antibodies to the D-domain were also detected in one of the CSF samples. Determination of IgG subclasses detected IgG1 in two sera and one CSF, IgG2 in none of the samples, IgG3 in two sera, and IgG4 in eight sera. One patient known to be positive for IgA antibodies to full-length synapsin had IgA antibodies to the D-domain in serum and CSF. Conclusions Anti-synapsin autoantibodies preferentially bind to either the A- or the D-domain of synapsin I.
UR - http://www.scopus.com/inward/record.url?scp=85058413832&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0208636
DO - 10.1371/journal.pone.0208636
M3 - Article
C2 - 30543686
AN - SCOPUS:85058413832
SN - 1932-6203
VL - 13
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e0208636
ER -