Document Type : Original Article
- Durgadevi Parthasarathy 1
- Kulandai Lily Therese 1
- Selvakumar Ambika 2
- Selvi Krishnan 1
- Durga Priyadarshini Santhakumar 2
1 L&T Microbiology Research Centre, Kamal Nayan Bajaj Building for Research in Vision and Opthalmology, Vision Research Foundation, Chennai, India
2 Department of Neuro-ophthalmology, Sankara Nethralaya Hospital, Medical Research Foundation, Chennai, India
Background: This study was aimed to test simultaneous detection of antibodies to myelin oligodendrocyte glycoprotein (MOG)/aquaporin‑4 (AQP4) in serum samples of patients with clinically-diagnosed optic neuritis (ON), by fixed cell-based immunofluorescence assay (CBIFA).
Methods: The study involved 237 serum samples of patients with ON which were tested for MOG and AQP4 antibodies using fixed CBIFA kit which utilizes AQP4 or MOG protein transfected cells as a substrate.
Results: Of 237 serum samples, 22 (9%) were positive for AQP4, 66 (28%) were positive for MOG, and 138 (58%) were negative for both AQP4 and MOG antibodies. 11 (5%) patients with clinically-diagnosed multiple sclerosis (MS) were negative for both antibodies. None of the samples were positive for both AQP4 and MOG. Among 237, 132 women [18 (13.6%) and 37 (28%)] and 105 men [4 (3.8%) and 29 (27.6%)] were positive for AQP4/MOG antibodies and remaining percentage belonged to double negative and MS. Seropositivity rate was higher in women than men. Antibodies to MOG were significantly higher than AQP4 antibodies and evenly found in all age groups. There was no ambiguous result encountered in the study.
Conclusion: In this study, the seropositivity for antibodies to MOG is more than AQP4 antibody in patients with ON. Fixed CBIFA is a useful tool for laboratory diagnosis of ON in the clinical setting of neuro-ophthalmology to plan the next line of treatment management effectively.
- Rodriguez M, Siva A, Cross SA, O'Brien PC, Kurland LT. Optic neuritis: A population-based study in Olmsted County, Minnesota. Neurology 1995; 45(2): 244-50.
- Takano R, Misu T, Takahashi T, Sato S, Fujihara K, Itoyama Y. Astrocytic damage is far more severe than demyelination in NMO: A clinical CSF biomarker study. Neurology 2010; 75(3): 208-16.
- Pandit L, Asgari N, Apiwattanakul M, Palace J, Paul F, Leite MI, et al. Demographic and clinical features of neuromyelitis optica: A review. Mult Scler 2015; 21(7): 845-53.
- Popescu BF, Lennon VA, Parisi JE, Howe CL, Weigand SD, Cabrera-Gomez JA, et al. Neuromyelitis optica unique area postrema lesions: Nausea, vomiting, and pathogenic implications. Neurology 2011; 76(14): 1229-37.
- Magana SM, Pittock SJ, Lennon VA, Keegan BM, Weinshenker BG, Lucchinetti CF. Neuromyelitis optica IgG serostatus in fulminant central nervous system inflammatory demyelinating disease. Arch Neurol 2009; 66(8): 964-6.
- Kitley J, Woodhall M, Waters P, Leite MI, Devenney E, Craig J, et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 2012; 79(12): 1273-7.
- Kitley J, Waters P, Woodhall M, Leite MI, Murchison A, George J, et al. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: A comparative study. JAMA Neurol 2014; 71(3): 276-83.
- Sato DK, Callegaro D, Lana-Peixoto MA, Waters PJ, de Haidar Jorge FM, Takahashi T, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014; 82(6): 474-81.
- Hoftberger R, Sepulveda M, Armangue T, Blanco Y, Rostasy K, Calvo AC, et al. Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease. Mult Scler 2015; 21(7): 866-74.
- Chang T, Waters P, Woodhall M, Vincent A. Recurrent optic neuritis associated with MOG antibody seropositivity. Neurologist 2017; 22(3): 101-2.
- Brilot F. Inflammation and autoimmunity: A nervous system perspective. In: Dale RC, Vincent A, editors. Inflammatory and autoimmune disorders of the nervous system in children. Hoboken, NJ: Wiley; 2010.
- Diamond B, Honig G, Mader S, Brimberg L, Volpe BT. Brain-reactive antibodies and disease. Annu Rev Immunol 2013; 31: 345-85.
- Constantinescu CS, Farooqi N, O'Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 2011; 164(4): 1079-106.
- Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85(2): 177-89.
- Prain K, Woodhall M, Vincent A, Ramanathan S, Barnett MH, Bundell CS, et al. AQP4 Antibody assay sensitivity comparison in the era of the 2015 diagnostic criteria for NMOSD. Front Neurol 2019; 10: 1028.
- Waters P, Woodhall M, O'Connor KC, Reindl M, Lang B, Sato DK, et al. MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflamm 2015; 2(3): e89.
- Reindl M, Schanda K, Woodhall M, Tea F, Ramanathan S, Sagen J, et al. International multicenter examination of MOG antibody assays. Neurol Neuroimmunol Neuroinflamm 2020; 7(2): e674.
- Waters PJ, Komorowski L, Woodhall M, Lederer S, Majed M, Fryer J, et al. A multicenter comparison of MOG-IgG
cell-based assays. Neurology 2019; 92(11): e1250-e1255.
- Kunchok A, Malpas C, Nytrova P, Havrdova EK, Alroughani R, Terzi M, et al. Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 2020; 38: 101868.
- Kim SM, Woodhall MR, Kim JS, Kim SJ, Park KS, Vincent A, et al. Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS. Neurol Neuroimmunol Neuroinflamm 2015; 2(6): e163.
- Weber MS, Derfuss T, Metz I, Bruck W. Defining distinct features of anti-MOG antibody associated central nervous system demyelination. Ther Adv Neurol Disord 2018; 11: 1756286418762083.
- Sellner J, Boggild M, Clanet M, Hintzen RQ, Illes Z, Montalban X, et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol 2010; 17(8): 1019-32.
- Etemadifar M, Abbasi M, Salari M, Etemadifar F, Tavakoli H. Comparing myelin oligodendrocyte glycoprotein antibody (MOG-Ab) and non MOG-Ab associated optic neuritis: Clinical course and treatment outcome. Mult Scler Relat Disord 2019; 27: 127-30.
- Ramanathan S, Mohammad S, Tantsis E, Nguyen TK, Merheb V, Fung VSC, et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry 2018; 89(2): 127-37.
- Zamvil SS, Slavin AJ. Does MOG Ig-positive AQP4-seronegative opticospinal inflammatory disease justify a diagnosis of NMO spectrum disorder? Neurol Neuroimmunol Neuroinflamm 2015; 2(1): e62.
- Deschamps R, Lecler A, Lamirel C, Aboab J, Gueguen A, Bensa C, et al. Etiologies of acute demyelinating optic neuritis: An observational study of 110 patients. Eur J Neurol 2017; 24(6): 875-9.
- Kim SH, Kim W, Li XF, Jung IJ, Kim HJ. Clinical spectrum of CNS aquaporin-4 autoimmunity. Neurology 2012; 78(15): 1179-85.
- Hennes EM, Baumann M, Lechner C, Rostasy K. MOG spectrum disorders and role of MOG-antibodies in clinical practice. Neuropediatrics 2018; 49(1): 3-11.
- Reindl M, Jarius S, Rostasy K, Berger T. Myelin oligodendrocyte glycoprotein antibodies: How clinically useful are they? Curr Opin Neurol 2017; 30(3): 295-301.
- Hacohen Y, Banwell B. Treatment approaches for MOG-Ab-Associated demyelination in children. Curr Treat Options Neurol 2019; 21(1): 2.
- Pfeuffer S, Strippel C, Wiendl H. NMO spectrum disorders. Neurology International Open 2017; 1(1): E36-E47.
- Zhao Y, Tan S, Chan TCY, Xu Q, Zhao J, Teng D, et al. Clinical features of demyelinating optic neuritis with seropositive myelin oligodendrocyte glycoprotein antibody in Chinese patients. Br J Ophthalmol 2018; 102(10): 1372-7.
- Zhao G, Chen Q, Huang Y, Li Z, Sun X, Lu P, et al. Clinical characteristics of myelin oligodendrocyte glycoprotein seropositive optic neuritis: A cohort study in Shanghai, China. J Neurol 2018; 265(1): 33-40.
- Soelberg K, Jarius S, Skejoe H, Engberg H, Mehlsen JJ, Nilsson AC, et al. A population-based prospective study of optic neuritis. Mult Scler 2017; 23(14): 1893-901.
- Hassan MB, Stern C, Flanagan EP, Pittock SJ, Kunchok A, Foster RC, et al. Population-based incidence of optic neuritis in the era of aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies. Am J Ophthalmol 2020; 220: 110-4.
- de Mol CL, Wong Y, van Pelt ED, Wokke B, Siepman T, Neuteboom RF, et al. The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults. Mult Scler 2020; 26(7): 806-14.
- Senanayake B, Jitprapaikulsan J, Aravinthan M, Wijesekera JC, Ranawaka UK, Riffsy MT, et al. Seroprevalence and clinical phenotype of MOG-IgG-associated disorders in Sri Lanka. J Neurol Neurosurg Psychiatry 2019; 90(12): 1381-3.