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Prevalence of Myelin Oligodendrocyte Glycoprotein and Aquaporin-4-IgG in Patients in the Optic Neuritis Treatment Trial.
JAMA Ophthalmol. 2018 04 01; 136(4):419-422.JO

Abstract

Importance

Autoantibodies to aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) are recently established biomarkers of autoimmune optic neuritis whose frequency and accompanying phenotype, especially for MOG-IgG, are still being characterized. The Optic Neuritis Treatment Trial (ONTT) was a well-known randomized clinical trial in optic neuritis; therefore, knowledge of the serostatus and accompanying phenotype of these patients would be useful to determine the frequency of these antibodies in patients presenting with typical monocular optic neuritis and their outcomes.

Objectives

To determine the AQP4-IgG and MOG-IgG serostatus of patients within the ONTT and describe the clinical features of seropositive patients.

Design, Setting, and Participants

In this follow-up study of the randomized clinical trial, ONTT, conducted between July 1, 1988, and June 30, 1991, analysis of serum for AQP4-IgG and MOG-IgG was performed from January 1 to April 30, 2017. A total of 177 patients from the ONTT with acute optic neuritis and serum available for analysis were enrolled from 13 academic referral centers.

Interventions

Analysis of serum for AQP4-IgG and MOG-IgG was performed at Mayo Clinic Neuroimmunology Laboratory in 2017 with a flow cytometry, live cell, AQP4- and MOG-transfected cell-based assay.

Main Outcomes and Measures

Aquaporin-4-IgG and MOG-IgG serostatus.

Results

Of the 177 patients in the study (135 women and 42 men; mean [SD] age, 32.8 [6.9] years), 3 were positive for MOG-IgG (1.7%) and none were positive for AQP4-IgG. All 3 patients positive for MOG-IgG had disc edema at presentation. Two patients later had a single episode of recurrent optic neuritis. All 3 patients had complete recovery of visual acuity, and none were corticosteroid dependent, although peripheral visual field loss persisted in 1 patient. None of the 3 patients positive for MOG-IgG had demyelinating lesions on magnetic resonance imaging scans, and none had developed multiple sclerosis at the 15-year follow-up.

Conclusions and Relevance

Frequency of MOG-IgG was rare in the ONTT, and AQP4-IgG was not found in patients in the ONTT. Characteristics of patients positive for MOG-IgG in the ONTT support the previously described phenotype of MOG-IgG optic neuritis. Myelin oligodendrocyte glycoprotein-related disease appears to be a different entity than multiple sclerosis. Overall, AQP4-IgG and MOG-IgG may be less common in isolated optic neuritis than previously reported.

Authors+Show Affiliations

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. Department of Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota.Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29470571

Citation

Chen, John J., et al. "Prevalence of Myelin Oligodendrocyte Glycoprotein and Aquaporin-4-IgG in Patients in the Optic Neuritis Treatment Trial." JAMA Ophthalmology, vol. 136, no. 4, 2018, pp. 419-422.
Chen JJ, Tobin WO, Majed M, et al. Prevalence of Myelin Oligodendrocyte Glycoprotein and Aquaporin-4-IgG in Patients in the Optic Neuritis Treatment Trial. JAMA Ophthalmol. 2018;136(4):419-422.
Chen, J. J., Tobin, W. O., Majed, M., Jitprapaikulsan, J., Fryer, J. P., Leavitt, J. A., Flanagan, E. P., McKeon, A., & Pittock, S. J. (2018). Prevalence of Myelin Oligodendrocyte Glycoprotein and Aquaporin-4-IgG in Patients in the Optic Neuritis Treatment Trial. JAMA Ophthalmology, 136(4), 419-422. https://doi.org/10.1001/jamaophthalmol.2017.6757
Chen JJ, et al. Prevalence of Myelin Oligodendrocyte Glycoprotein and Aquaporin-4-IgG in Patients in the Optic Neuritis Treatment Trial. JAMA Ophthalmol. 2018 04 1;136(4):419-422. PubMed PMID: 29470571.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevalence of Myelin Oligodendrocyte Glycoprotein and Aquaporin-4-IgG in Patients in the Optic Neuritis Treatment Trial. AU - Chen,John J, AU - Tobin,W Oliver, AU - Majed,Masoud, AU - Jitprapaikulsan,Jiraporn, AU - Fryer,James P, AU - Leavitt,Jacqueline A, AU - Flanagan,Eoin P, AU - McKeon,Andrew, AU - Pittock,Sean J, PY - 2018/2/23/pubmed PY - 2019/9/13/medline PY - 2018/2/23/entrez SP - 419 EP - 422 JF - JAMA ophthalmology JO - JAMA Ophthalmol VL - 136 IS - 4 N2 - Importance: Autoantibodies to aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) are recently established biomarkers of autoimmune optic neuritis whose frequency and accompanying phenotype, especially for MOG-IgG, are still being characterized. The Optic Neuritis Treatment Trial (ONTT) was a well-known randomized clinical trial in optic neuritis; therefore, knowledge of the serostatus and accompanying phenotype of these patients would be useful to determine the frequency of these antibodies in patients presenting with typical monocular optic neuritis and their outcomes. Objectives: To determine the AQP4-IgG and MOG-IgG serostatus of patients within the ONTT and describe the clinical features of seropositive patients. Design, Setting, and Participants: In this follow-up study of the randomized clinical trial, ONTT, conducted between July 1, 1988, and June 30, 1991, analysis of serum for AQP4-IgG and MOG-IgG was performed from January 1 to April 30, 2017. A total of 177 patients from the ONTT with acute optic neuritis and serum available for analysis were enrolled from 13 academic referral centers. Interventions: Analysis of serum for AQP4-IgG and MOG-IgG was performed at Mayo Clinic Neuroimmunology Laboratory in 2017 with a flow cytometry, live cell, AQP4- and MOG-transfected cell-based assay. Main Outcomes and Measures: Aquaporin-4-IgG and MOG-IgG serostatus. Results: Of the 177 patients in the study (135 women and 42 men; mean [SD] age, 32.8 [6.9] years), 3 were positive for MOG-IgG (1.7%) and none were positive for AQP4-IgG. All 3 patients positive for MOG-IgG had disc edema at presentation. Two patients later had a single episode of recurrent optic neuritis. All 3 patients had complete recovery of visual acuity, and none were corticosteroid dependent, although peripheral visual field loss persisted in 1 patient. None of the 3 patients positive for MOG-IgG had demyelinating lesions on magnetic resonance imaging scans, and none had developed multiple sclerosis at the 15-year follow-up. Conclusions and Relevance: Frequency of MOG-IgG was rare in the ONTT, and AQP4-IgG was not found in patients in the ONTT. Characteristics of patients positive for MOG-IgG in the ONTT support the previously described phenotype of MOG-IgG optic neuritis. Myelin oligodendrocyte glycoprotein-related disease appears to be a different entity than multiple sclerosis. Overall, AQP4-IgG and MOG-IgG may be less common in isolated optic neuritis than previously reported. SN - 2168-6173 UR - https://www.unboundmedicine.com/medline/citation/29470571/Prevalence_of_Myelin_Oligodendrocyte_Glycoprotein_and_Aquaporin_4_IgG_in_Patients_in_the_Optic_Neuritis_Treatment_Trial_ L2 - https://jamanetwork.com/journals/jamaophthalmology/fullarticle/10.1001/jamaophthalmol.2017.6757 DB - PRIME DP - Unbound Medicine ER -