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Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG-Associated Disorders.
JAMA Neurol. 2018 11 01; 75(11):1355-1363.JN

Abstract

Importance

Recent studies have reported a higher relapse rate following an initial inflammatory demyelinating disorder in pediatric patients with persistent seropositivity of antibodies targeting myelin oligodendrocyte glycoprotein (MOG-IgG1). To date, the clinical implications of longitudinal MOG-IgG1 seropositivity using live cell assays with IgG1 secondary antibodies in adults after acute disseminated encephalomyelitis (ADEM) are unknown.

Objective

To determine whether MOG-IgG1 serostatus (transient vs persistent) and titer change over time provide clinical utility in predicting the likelihood of relapse after ADEM.

Design, Setting, and Participants

This cohort study identified patients with an initial diagnosis of ADEM evaluated at a single referral center between January 1, 1990, and October 1, 2017. Fifty-one patients were included, including 31 children and 20 adults. Longitudinal serologic testing was performed detecting autoantibodies targeting aquaporin 4 (AQP4-IgG) and MOG-IgG1 with clinically validated fluorescence-activated cell sorting assays. Patients were divided into 3 cohorts: persistent seropositivity, transient seropositivity, and seronegativity.

Main Outcomes and Measures

Clinical demographic characteristics, longitudinal AQP4-IgG and MOG-IgG1 serostatus, titers, relapses, use of immunotherapy, and Expanded Disability Status Scale score at follow-up.

Results

Of 51 patients presenting with an initial diagnosis of ADEM, 20 (39%) were adult, 24 (47%) were female, and ages ranged from 12 months to 57 years. Seventeen patients fulfilled criteria for persistent seropositivity; of those, 8 of 9 children (89%) and 7 of 8 adults (88%) had at least 1 relapse after median (range) follow-up periods of 75 (15-236) months and 39 (9-161) months, respectively. Eight patients (16%), including 4 adults, fulfilled criteria for transient seropositivity; of those, no children and 1 of 4 adults (25%) relapsed after median (range) follow-up periods of 32 (24-114) months and 16 (13-27) months, respectively. Of 24 patients with AQP4-IgG and MOG-IgG seronegativity, 6 of 17 children (35%) and 2 of 7 adults (29%) had at least 1 relapse after median (range) follow-up periods of 36 (3-203) months and 34 (15-217) months, respectively. There were only 2 patients, including 1 adult, with AQP4-IgG seropositivity, and both relapsed. The hazard ratio for relapses in those with persistent MOG-IgG1 positivity compared with AQP4-IgG and MOG-IgG1 seronegativity was 3.1 (95% CI, 1.1-8.9; P = .04) in children and 5.5 (95% CI, 1.4-22.5; P = .02) in adults. Immunotherapy was used in 5 of 9 children (56%) and 6 of 8 adults (75%) with persistent seropositivity and in 3 of 17 children (18%) and 1 of 7 adults (14%) with AQP4-IgG and MOG-IgG seronegativity.

Conclusions and Relevance

Relapse occurred in 15 of 17 patients (88%) with persistent MOG-IgG1 seropositivity after ADEM; only 1 patient with transient seropositivity experienced relapse. Our data extend the clinical utility of MOG-IgG1 serological testing to adult patients and highlights that longitudinal serologic evaluation of MOG-IgG1 could help predict disease course and consideration of immunotherapy.

Authors+Show Affiliations

Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Department of Neurology, Mayo Clinic, Scottsdale, Arizona.Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota. Department of Immunology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30014148

Citation

López-Chiriboga, A Sebastian, et al. "Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG-Associated Disorders." JAMA Neurology, vol. 75, no. 11, 2018, pp. 1355-1363.
López-Chiriboga AS, Majed M, Fryer J, et al. Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG-Associated Disorders. JAMA Neurol. 2018;75(11):1355-1363.
López-Chiriboga, A. S., Majed, M., Fryer, J., Dubey, D., McKeon, A., Flanagan, E. P., Jitprapaikulsan, J., Kothapalli, N., Tillema, J. M., Chen, J., Weinshenker, B., Wingerchuk, D., Sagen, J., Gadoth, A., Lennon, V. A., Keegan, B. M., Lucchinetti, C., & Pittock, S. J. (2018). Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG-Associated Disorders. JAMA Neurology, 75(11), 1355-1363. https://doi.org/10.1001/jamaneurol.2018.1814
López-Chiriboga AS, et al. Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG-Associated Disorders. JAMA Neurol. 2018 11 1;75(11):1355-1363. PubMed PMID: 30014148.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG-Associated Disorders. AU - López-Chiriboga,A Sebastian, AU - Majed,Masoud, AU - Fryer,James, AU - Dubey,Divyanshu, AU - McKeon,Andrew, AU - Flanagan,Eoin P, AU - Jitprapaikulsan,Jiraporn, AU - Kothapalli,Naga, AU - Tillema,Jan-Mendelt, AU - Chen,John, AU - Weinshenker,Brian, AU - Wingerchuk,Dean, AU - Sagen,Jessica, AU - Gadoth,Avi, AU - Lennon,Vanda A, AU - Keegan,B Mark, AU - Lucchinetti,Claudia, AU - Pittock,Sean J, PY - 2018/7/18/pubmed PY - 2019/10/11/medline PY - 2018/7/18/entrez SP - 1355 EP - 1363 JF - JAMA neurology JO - JAMA Neurol VL - 75 IS - 11 N2 - Importance: Recent studies have reported a higher relapse rate following an initial inflammatory demyelinating disorder in pediatric patients with persistent seropositivity of antibodies targeting myelin oligodendrocyte glycoprotein (MOG-IgG1). To date, the clinical implications of longitudinal MOG-IgG1 seropositivity using live cell assays with IgG1 secondary antibodies in adults after acute disseminated encephalomyelitis (ADEM) are unknown. Objective: To determine whether MOG-IgG1 serostatus (transient vs persistent) and titer change over time provide clinical utility in predicting the likelihood of relapse after ADEM. Design, Setting, and Participants: This cohort study identified patients with an initial diagnosis of ADEM evaluated at a single referral center between January 1, 1990, and October 1, 2017. Fifty-one patients were included, including 31 children and 20 adults. Longitudinal serologic testing was performed detecting autoantibodies targeting aquaporin 4 (AQP4-IgG) and MOG-IgG1 with clinically validated fluorescence-activated cell sorting assays. Patients were divided into 3 cohorts: persistent seropositivity, transient seropositivity, and seronegativity. Main Outcomes and Measures: Clinical demographic characteristics, longitudinal AQP4-IgG and MOG-IgG1 serostatus, titers, relapses, use of immunotherapy, and Expanded Disability Status Scale score at follow-up. Results: Of 51 patients presenting with an initial diagnosis of ADEM, 20 (39%) were adult, 24 (47%) were female, and ages ranged from 12 months to 57 years. Seventeen patients fulfilled criteria for persistent seropositivity; of those, 8 of 9 children (89%) and 7 of 8 adults (88%) had at least 1 relapse after median (range) follow-up periods of 75 (15-236) months and 39 (9-161) months, respectively. Eight patients (16%), including 4 adults, fulfilled criteria for transient seropositivity; of those, no children and 1 of 4 adults (25%) relapsed after median (range) follow-up periods of 32 (24-114) months and 16 (13-27) months, respectively. Of 24 patients with AQP4-IgG and MOG-IgG seronegativity, 6 of 17 children (35%) and 2 of 7 adults (29%) had at least 1 relapse after median (range) follow-up periods of 36 (3-203) months and 34 (15-217) months, respectively. There were only 2 patients, including 1 adult, with AQP4-IgG seropositivity, and both relapsed. The hazard ratio for relapses in those with persistent MOG-IgG1 positivity compared with AQP4-IgG and MOG-IgG1 seronegativity was 3.1 (95% CI, 1.1-8.9; P = .04) in children and 5.5 (95% CI, 1.4-22.5; P = .02) in adults. Immunotherapy was used in 5 of 9 children (56%) and 6 of 8 adults (75%) with persistent seropositivity and in 3 of 17 children (18%) and 1 of 7 adults (14%) with AQP4-IgG and MOG-IgG seronegativity. Conclusions and Relevance: Relapse occurred in 15 of 17 patients (88%) with persistent MOG-IgG1 seropositivity after ADEM; only 1 patient with transient seropositivity experienced relapse. Our data extend the clinical utility of MOG-IgG1 serological testing to adult patients and highlights that longitudinal serologic evaluation of MOG-IgG1 could help predict disease course and consideration of immunotherapy. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/30014148/Association_of_MOG_IgG_Serostatus_With_Relapse_After_Acute_Disseminated_Encephalomyelitis_and_Proposed_Diagnostic_Criteria_for_MOG_IgG_Associated_Disorders_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2018.1814 DB - PRIME DP - Unbound Medicine ER -