Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination
Abstract Over 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 beco...
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BMC
2019-09-01
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Series: | Acta Neuropathologica Communications |
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Online Access: | http://link.springer.com/article/10.1186/s40478-019-0786-3 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fiona Tea Joseph A. Lopez Sudarshini Ramanathan Vera Merheb Fiona X. Z. Lee Alicia Zou Deepti Pilli Ellis Patrick Anneke van der Walt Mastura Monif Esther M. Tantsis Eppie M. Yiu Steve Vucic Andrew P. D. Henderson Anthony Fok Clare L. Fraser Jeanette Lechner-Scott Stephen W. Reddel Simon Broadley Michael H. Barnett David A. Brown Jan D. Lunemann Russell C. Dale Fabienne Brilot the Australasian and New Zealand MOG Study Group |
spellingShingle |
Fiona Tea Joseph A. Lopez Sudarshini Ramanathan Vera Merheb Fiona X. Z. Lee Alicia Zou Deepti Pilli Ellis Patrick Anneke van der Walt Mastura Monif Esther M. Tantsis Eppie M. Yiu Steve Vucic Andrew P. D. Henderson Anthony Fok Clare L. Fraser Jeanette Lechner-Scott Stephen W. Reddel Simon Broadley Michael H. Barnett David A. Brown Jan D. Lunemann Russell C. Dale Fabienne Brilot the Australasian and New Zealand MOG Study Group Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination Acta Neuropathologica Communications Myelin oligodendrocyte glycoprotein Antibody Epitope, antigen conformation Optic neuritis Multiple sclerosis Diagnosis |
author_facet |
Fiona Tea Joseph A. Lopez Sudarshini Ramanathan Vera Merheb Fiona X. Z. Lee Alicia Zou Deepti Pilli Ellis Patrick Anneke van der Walt Mastura Monif Esther M. Tantsis Eppie M. Yiu Steve Vucic Andrew P. D. Henderson Anthony Fok Clare L. Fraser Jeanette Lechner-Scott Stephen W. Reddel Simon Broadley Michael H. Barnett David A. Brown Jan D. Lunemann Russell C. Dale Fabienne Brilot the Australasian and New Zealand MOG Study Group |
author_sort |
Fiona Tea |
title |
Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination |
title_short |
Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination |
title_full |
Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination |
title_fullStr |
Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination |
title_full_unstemmed |
Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination |
title_sort |
characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2019-09-01 |
description |
Abstract Over 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. |
topic |
Myelin oligodendrocyte glycoprotein Antibody Epitope, antigen conformation Optic neuritis Multiple sclerosis Diagnosis |
url |
http://link.springer.com/article/10.1186/s40478-019-0786-3 |
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doaj-607b345479a846fb9c66797c81d8bfbb2020-11-25T02:52:59ZengBMCActa Neuropathologica Communications2051-59602019-09-017112210.1186/s40478-019-0786-3Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelinationFiona Tea0Joseph A. Lopez1Sudarshini Ramanathan2Vera Merheb3Fiona X. Z. Lee4Alicia Zou5Deepti Pilli6Ellis Patrick7Anneke van der Walt8Mastura Monif9Esther M. Tantsis10Eppie M. Yiu11Steve Vucic12Andrew P. D. Henderson13Anthony Fok14Clare L. Fraser15Jeanette Lechner-Scott16Stephen W. Reddel17Simon Broadley18Michael H. Barnett19David A. Brown20Jan D. Lunemann21Russell C. Dale22Fabienne Brilot23the Australasian and New Zealand MOG Study GroupBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadDiscipline of Applied Medical Science, The University of SydneyDepartment of Neurosciences, Central Clinical School, Monash UniversityDepartment of Neurosciences, Central Clinical School, Monash UniversityBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadDepartment of Neurology, Royal Children’s Hospital and Neurosciences Research, Murdoch Children’s Research InstituteDepartment of Neurology, Westmead HospitalDepartment of Neurology, Westmead HospitalDepartment of Neurology, Monash HealthSave Sight Institute, Faculty of Medicine and Health, The University of SydneyHunter Medical Research InstituteBrain and Mind Centre, The University of SydneyDepartment of Neurology, School of Medicine, Gold Coast University Hospital, Griffith UniversityBrain and Mind Centre, The University of SydneyNew South Wales Health Pathology, Institute of Clinical Pathology and Medical Research, and Westmead Institute for Medical Research, The University of SydneyDepartment of Neurology, University of MünsterBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadBrain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at WestmeadAbstract Over 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.http://link.springer.com/article/10.1186/s40478-019-0786-3Myelin oligodendrocyte glycoproteinAntibodyEpitope, antigen conformationOptic neuritisMultiple sclerosisDiagnosis |