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Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis.
Ophthalmology. 2018 10; 125(10):1628-1637.O

Abstract

PURPOSE

To determine the aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) serostatus and visual outcomes in patients with recurrent optic neuritis (rON) initially seeking treatment.

DESIGN

Cross-sectional cohort study.

PARTICIPANTS

The study identified patients by searching the Mayo Clinic computerized central diagnostic index (January 2000-March 2017). The 246 eligible patients fulfilled the following criteria: (1) initially seeking treatment for at least 2 consecutive episodes of optic neuritis (ON) and (2) serum available for testing.

METHODS

Serum was tested for aquaporin-4 IgG and MOG IgG1 using an in-house validated flow cytometric assay using live HEK293 cells transfected with M1 aquaporin-4 or full-length MOG.

MAIN OUTCOMES MEASURES

Aquaporin-4 IgG and MOG IgG1 serostatus, clinical characteristics, and visual outcomes.

RESULTS

Among 246 patients with rON at presentation, glial autoantibodies were detected in 32% (aquaporin-4 IgG, 19%; MOG IgG1, 13%); 186 patients had rON only and 60 patients had rON with subsequent additional inflammatory demyelinating attacks (rON-plus group). The rON-only cohort comprised the following: double seronegative (idiopathic), 110 patients (59%); MOG IgG1 positive, 27 patients (15%; 4 with chronic relapsing inflammatory optic neuropathy); multiple sclerosis (MS), 25 patients (13%); and aquaporin-4 IgG positive, 24 patients (13%). The rON-plus cohort comprised the following: aquaporin-4 IgG positive, 23 patients (38%); MS, 22 patients (37%); double seronegative, 11 patients (18%); and MOG IgG1 positive, 4 patients (7%). The annualized relapse rate for the rON-only group was 1.2 for MOG IgG1-positive patients, 0.7 for double-seronegative patients, 0.6 for aquaporin-4 IgG-positive patients, and 0.4 for MS patients (P = 0.005). The median visual acuity (VA) of patients with the worst rON-only attack at nadir were hand movements in aquaporin-4 IgG-positive patients, between counting fingers and hand movements in MOG IgG1-positive patients, 20/800 in idiopathic patients, and 20/100 in MS patients (P = 0.02). The median VA at last follow-up for affected eyes of the rON-only cohort were counting fingers for aquaporin-4 IgG-positive patients, 20/40 for idiopathic patients, 20/25 for MS patients and MOG IgG1-positive patients (P = 0.006). At 5 years after ON onset, 59% of aquaporin-4 IgG-positive patients, 22% of idiopathic patients, 12% of MOG IgG1-positive patients, and 8% of MS patients were estimated to have severe visual loss.

CONCLUSIONS

Glial autoantibodies (MOG IgG1 or aquaporin-4 IgG) are found in one third of all patients with rON. Aquaporin-4 IgG seropositivity predicts a worse visual outcome than MOG IgG1 seropositivity, double seronegativity, or MS diagnosis. Myelin oligodendrocyte glycoprotein IgG1 is associated with a greater relapse rate but better visual outcomes.

Authors+Show Affiliations

Department of Neurology, Mayo Clinic, Rochester, Minnesota; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota; Department of Immunology, Mayo Clinic, Rochester, Minnesota.Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.Department of Neurology, Mayo Clinic, Rochester, Minnesota; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Center for MS and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. Electronic address: pittock.sean@mayo.edu.

Pub Type(s)

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

Language

eng

PubMed ID

29716788

Citation

Jitprapaikulsan, Jiraporn, et al. "Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis." Ophthalmology, vol. 125, no. 10, 2018, pp. 1628-1637.
Jitprapaikulsan J, Chen JJ, Flanagan EP, et al. Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis. Ophthalmology. 2018;125(10):1628-1637.
Jitprapaikulsan, J., Chen, J. J., Flanagan, E. P., Tobin, W. O., Fryer, J. P., Weinshenker, B. G., McKeon, A., Lennon, V. A., Leavitt, J. A., Tillema, J. M., Lucchinetti, C., Keegan, B. M., Kantarci, O., Khanna, C., Jenkins, S. M., Spears, G. M., Sagan, J., & Pittock, S. J. (2018). Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis. Ophthalmology, 125(10), 1628-1637. https://doi.org/10.1016/j.ophtha.2018.03.041
Jitprapaikulsan J, et al. Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis. Ophthalmology. 2018;125(10):1628-1637. PubMed PMID: 29716788.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis. AU - Jitprapaikulsan,Jiraporn, AU - Chen,John J, AU - Flanagan,Eoin P, AU - Tobin,W Oliver, AU - Fryer,Jim P, AU - Weinshenker,Brian G, AU - McKeon,Andrew, AU - Lennon,Vanda A, AU - Leavitt,Jacqueline A, AU - Tillema,Jan-Mendelt, AU - Lucchinetti,Claudia, AU - Keegan,B Mark, AU - Kantarci,Orhun, AU - Khanna,Cheryl, AU - Jenkins,Sarah M, AU - Spears,Grant M, AU - Sagan,Jessica, AU - Pittock,Sean J, Y1 - 2018/04/30/ PY - 2018/01/23/received PY - 2018/03/20/revised PY - 2018/03/21/accepted PY - 2018/5/3/pubmed PY - 2019/9/7/medline PY - 2018/5/3/entrez SP - 1628 EP - 1637 JF - Ophthalmology JO - Ophthalmology VL - 125 IS - 10 N2 - PURPOSE: To determine the aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) serostatus and visual outcomes in patients with recurrent optic neuritis (rON) initially seeking treatment. DESIGN: Cross-sectional cohort study. PARTICIPANTS: The study identified patients by searching the Mayo Clinic computerized central diagnostic index (January 2000-March 2017). The 246 eligible patients fulfilled the following criteria: (1) initially seeking treatment for at least 2 consecutive episodes of optic neuritis (ON) and (2) serum available for testing. METHODS: Serum was tested for aquaporin-4 IgG and MOG IgG1 using an in-house validated flow cytometric assay using live HEK293 cells transfected with M1 aquaporin-4 or full-length MOG. MAIN OUTCOMES MEASURES: Aquaporin-4 IgG and MOG IgG1 serostatus, clinical characteristics, and visual outcomes. RESULTS: Among 246 patients with rON at presentation, glial autoantibodies were detected in 32% (aquaporin-4 IgG, 19%; MOG IgG1, 13%); 186 patients had rON only and 60 patients had rON with subsequent additional inflammatory demyelinating attacks (rON-plus group). The rON-only cohort comprised the following: double seronegative (idiopathic), 110 patients (59%); MOG IgG1 positive, 27 patients (15%; 4 with chronic relapsing inflammatory optic neuropathy); multiple sclerosis (MS), 25 patients (13%); and aquaporin-4 IgG positive, 24 patients (13%). The rON-plus cohort comprised the following: aquaporin-4 IgG positive, 23 patients (38%); MS, 22 patients (37%); double seronegative, 11 patients (18%); and MOG IgG1 positive, 4 patients (7%). The annualized relapse rate for the rON-only group was 1.2 for MOG IgG1-positive patients, 0.7 for double-seronegative patients, 0.6 for aquaporin-4 IgG-positive patients, and 0.4 for MS patients (P = 0.005). The median visual acuity (VA) of patients with the worst rON-only attack at nadir were hand movements in aquaporin-4 IgG-positive patients, between counting fingers and hand movements in MOG IgG1-positive patients, 20/800 in idiopathic patients, and 20/100 in MS patients (P = 0.02). The median VA at last follow-up for affected eyes of the rON-only cohort were counting fingers for aquaporin-4 IgG-positive patients, 20/40 for idiopathic patients, 20/25 for MS patients and MOG IgG1-positive patients (P = 0.006). At 5 years after ON onset, 59% of aquaporin-4 IgG-positive patients, 22% of idiopathic patients, 12% of MOG IgG1-positive patients, and 8% of MS patients were estimated to have severe visual loss. CONCLUSIONS: Glial autoantibodies (MOG IgG1 or aquaporin-4 IgG) are found in one third of all patients with rON. Aquaporin-4 IgG seropositivity predicts a worse visual outcome than MOG IgG1 seropositivity, double seronegativity, or MS diagnosis. Myelin oligodendrocyte glycoprotein IgG1 is associated with a greater relapse rate but better visual outcomes. SN - 1549-4713 UR - https://www.unboundmedicine.com/medline/citation/29716788/Aquaporin_4_and_Myelin_Oligodendrocyte_Glycoprotein_Autoantibody_Status_Predict_Outcome_of_Recurrent_Optic_Neuritis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-6420(18)30240-9 DB - PRIME DP - Unbound Medicine ER -