Files and links (2)
Published (Version of Record)CC BY V4.0, Open Access
Journal article
Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination
Acta neuropathologica communications, Vol.7(1), 145
2019
PMCID: PMC6724269
PMID: 31481127
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.
Details
- Title
- Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination
- Authors/Creators
- Fiona Tea - Childrens Hosp Westmead, Kids Res, Kids Neurosci Ctr, Brain Autoimmun Grp, Locked Bag 4001, Sydney, NSW 2145, AustraliaJoseph A. Lopez - Childrens Hosp Westmead, Kids Res, Kids Neurosci Ctr, Brain Autoimmun Grp, Locked Bag 4001, Sydney, NSW 2145, AustraliaSudarshini Ramanathan - The University of SydneyVera Merheb - The University of SydneyFiona X. Z. Lee - Children's Hospital at WestmeadAlicia Zou - Children's Hospital at WestmeadDeepti Pilli - The University of SydneyEllis Patrick - The University of SydneyAnneke van der Walt - The University of SydneyMastura Monif - Monash UniversityEsther M. Tantsis - Monash UniversityEppie M. Yiu - The University of SydneySteve Vucic - The University of MelbourneAndrew P. D. Henderson - Westmead Hosp, Dept Neurol, Sydney, NSW, AustraliaAnthony Fok - Westmead HospitalClare L. Fraser - Monash HealthJeanette Lechner-Scott - College Station Medical CenterStephen W. Reddel - Hunter Medical Research InstituteSimon Broadley - The University of SydneyMichael H. Barnett - Gold Coast HospitalDavid A. Brown - The University of SydneyJan D. Lunemann - Westmead Institute for Medical ResearchRussell C. Dale - University of MünsterFabienne Brilot - The University of Sydney
- Contributors
- Allan G Kermode (Author) - Murdoch University, Institute for Immunology and Infectious DiseasesThe Australasian and New Zealand MOG Study Group (Institution)
- Publication Details
- Acta neuropathologica communications, Vol.7(1), 145
- Publisher
- Springer Nature
- Number of pages
- 22
- Grant note
- National Health and Medical Research Council (Australia); National Health and Medical Research Council (NHMRC) of Australia Ian Potter Foundation Multiple Sclerosis Research Australia Cancer Institute New South Wales Sydney Research Excellence Initiative 2020 (The University of Sydney, Australia) National Health and Medical Research Council; National Health and Medical Research Council (NHMRC) of Australia
- Identifiers
- 991005624466807891
- Copyright
- © The Author(s).
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Metrics
30 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Neurosciences
- ESI research areas
- Biology & Biochemistry