Show simple item record

dc.contributor.authorTea, Fiona
dc.contributor.authorLopez, Joseph A
dc.contributor.authorRamanathan, Sudarshini
dc.contributor.authorMerheb, Vera
dc.contributor.authorLee, Fiona XZ
dc.contributor.authorZou, Alicia
dc.contributor.authorPilli, Deepti
dc.contributor.authorPatrick, Ellis
dc.contributor.authorvan der Walt, Anneke
dc.contributor.authorMonif, Mastura
dc.contributor.authorTantsis, Esther M
dc.contributor.authorYiu, Eppie M
dc.contributor.authorVucic, Steve
dc.contributor.authorHenderson, Andrew PD
dc.contributor.authorFok, Anthony
dc.contributor.authorFraser, Clare L
dc.contributor.authorLechner-Scott, Jeanette
dc.contributor.authorReddel, Stephen W
dc.contributor.authorBroadley, Simon
dc.contributor.authorBarnett, Michael H
dc.contributor.authorBrown, David A
dc.contributor.authorLunemann, Jan D
dc.contributor.authorDale, Russell C
dc.contributor.authorBrilot, Fabienne
dc.contributor.authorAustralasian and New Zealand MOG Study Group
dc.date.accessioned2019-09-13T01:39:23Z
dc.date.available2019-09-13T01:39:23Z
dc.date.issued2019
dc.identifier.issn2051-5960
dc.identifier.doi10.1186/s40478-019-0786-3
dc.identifier.urihttp://hdl.handle.net/10072/387297
dc.description.abstractOver recent years, human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have been associated with monophasic and relapsing central nervous system demyelination involving the optic nerves, spinal cord, and brain. While the clinical relevance of MOG Ab detection is becoming increasingly clear as therapeutic and prognostic differences from multiple sclerosis are acknowledged, an in-depth characterization of human MOG Ab is required to answer key challenges in patient diagnosis, treatment, and prognosis. Herein, we investigated the epitope, binding sensitivity, and affinity of MOG Ab in a cohort of 139 and 148 MOG antibody-seropositive children and adults (n = 287 patients at baseline, 130 longitudinal samples, and 22 cerebrospinal fluid samples). MOG extracellular domain was also immobilized to determine the affinity of MOG Ab. MOG Ab response was of immunoglobulin G1 isotype, and was of peripheral rather than intrathecal origin. High affinity MOG Ab were detected in 15% paediatric and 18% adult sera. More than 75% of paediatric and adult MOG Ab targeted a dominant extracellular antigenic region around Proline42. MOG Ab titers fluctuated over the progression of disease, but affinity and reactivity to Proline42 remained stable. Adults with a relapsing course intrinsically presented with a reduced immunoreactivity to Proline42 and had a more diverse MOG Ab response, a feature that may be harnessed for predicting relapse. Higher titers of MOG Ab were observed in more severe phenotypes and during active disease, supporting the pathogenic role of MOG Ab. Loss of MOG Ab seropositivity was observed upon conformational changes to MOG, and this greatly impacted the sensitivity of the detection of relapsing disorders, largely considered as more severe. Careful consideration of the binding characteristics of autoantigens should be taken into account when detecting disease-relevant autoantibodies.
dc.description.peerreviewedYes
dc.description.sponsorshipMultiple Sclerosis Australia
dc.description.sponsorshipMultiple Sclerosis Research Australia
dc.description.sponsorshipMultiple Sclerosis Research Australia
dc.description.sponsorshipBrain Foundation
dc.description.sponsorshipGriffith University
dc.description.sponsorshipGriffith University
dc.description.sponsorshipGriffith University
dc.description.sponsorshipMerck Serono Australia Pty Ltd
dc.languageEnglish
dc.language.isoeng
dc.publisherBioMed Central
dc.publisher.placeUnited Kingdom
dc.relation.ispartofpagefrom145:1
dc.relation.ispartofpageto145:22
dc.relation.ispartofissue1
dc.relation.ispartofjournalActa Neuropathologica Communications
dc.relation.ispartofvolume7
dc.relation.urihttp://purl.org/au-research/grants/NHMRC/LP0776744
dc.relation.urihttp://purl.org/au-research/grants/NHMRC/DP180100089
dc.relation.urihttp://purl.org/au-research/grants/NHMRC/APP1047180
dc.relation.urihttp://purl.org/au-research/grants/NHMRC/APP1127819�
dc.relation.urihttp://purl.org/au-research/grants/ARC/LP0776744
dc.relation.urihttp://purl.org/au-research/grants/ARC/DP180100089
dc.relation.urihttp://purl.org/au-research/grants/ARC/APP1047180
dc.relation.urihttp://purl.org/au-research/grants/ARC/APP1127819�
dc.relation.grantIDLP0776744
dc.relation.grantIDDP180100089
dc.relation.grantIDAPP1047180
dc.relation.grantIDAPP1127819�
dc.relation.fundersNHMRC
dc.relation.fundersARC
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchNeurosciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode3209
dc.subject.keywordsAntibody
dc.subject.keywordsDiagnosis
dc.subject.keywordsEpitope, antigen conformation
dc.subject.keywordsMultiple sclerosis
dc.subject.keywordsMyelin oligodendrocyte glycoprotein
dc.titleCharacterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationTea, F; Lopez, JA; Ramanathan, S; Merheb, V; Lee, FXZ; Zou, A; Pilli, D; Patrick, E; van der Walt, A; Monif, M; Tantsis, EM; Yiu, EM; Vucic, S; Henderson, APD; Fok, A; Fraser, CL; Lechner-Scott, J; Reddel, SW; Broadley, S; Barnett, MH; Brown, DA; Lunemann, JD; Dale, RC; Brilot, F; Australasian and New Zealand MOG Study Group, Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination, Acta Neuropathologica Communications, 2019, 7 (1), pp. 145:1-145:22
dcterms.dateAccepted2019-08-09
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2019-09-12T23:50:52Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s). 2019 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.
gro.hasfulltextFull Text
gro.griffith.authorBroadley, Simon
gro.griffith.authorO'Gorman, Cullen


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record