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LETTERS TO THE EDITOR
Year : 2022  |  Volume : 25  |  Issue : 6  |  Page : 1227-1230
 

MOG antibody disease with non-neurological involvement: A chance coincidence or a relevant association


1 Department of Neurology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Radiodiagnosis, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

Date of Submission12-Jun-2022
Date of Decision17-Jul-2022
Date of Acceptance30-Jul-2022
Date of Web Publication3-Dec-2022

Correspondence Address:
Sanjeev K Bhoi
Additional Professor, Department of Neurology, All India Institute of Medical Sciences, Bhubaneswar, Odisha - 751 019
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aian.aian_520_22

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How to cite this article:
Porey C, Bhoi SK, Jha M, Naik S. MOG antibody disease with non-neurological involvement: A chance coincidence or a relevant association. Ann Indian Acad Neurol 2022;25:1227-30

How to cite this URL:
Porey C, Bhoi SK, Jha M, Naik S. MOG antibody disease with non-neurological involvement: A chance coincidence or a relevant association. Ann Indian Acad Neurol [serial online] 2022 [cited 2023 Jan 29];25:1227-30. Available from: https://www.annalsofian.org/text.asp?2022/25/6/1227/361562




Dear Sir,

Myelin oligodendrocyte glycoprotein (MOG) is a minor component of the myelin sheath and is thought to act as a cellular adhesive molecule, as a regulator of oligodendrocyte microtubule stability and a mediator of complement activation cascade.[1] The extracellular immunoglobulin variable domain and peripheral location in the sheath structure make MOG prone to antibody-mediated damage resulting in demyelination. The majority of MOG-IgG-seropositive cases have one or more features of optic neuritis, encephalitis with brain demyelinating lesions, or myelitis. MOG antibody disease (MOGAD) though considered to be exclusively a CNS disease, here we report two unique cases of MOGAD with associated non-neurological manifestations and review on whether they are more than a mere chance association.

CASE 1: A 43-year-old non-diabetic non-hypertensive gentleman with recurrent attacks of optic neuritis, hemiparesis and incoordination over a span of 6 years with good recovery every time in between episodes. Details of the attacks with corresponding MRI changes and relevant investigations are given in [Table 1] and [Figure 1]. A striking feature about this case was noted on routine urine analysis that showed evidence of asymptomatic proteinuria with 24-h urine protein level of around 1.6 gm without evidence of hematuria. Urine microalbumin was 576 mg/dl (0.2–1.9 mg/dl) and ACR was 2883 mg/gm creatinine (macroalbuminuria >300 mg/gm creatinine), and serum albumin levels were normal. On further evaluation, kidney core biopsy revealed podocytopathy with preservation of other glomerular, tubular, and vascular elements. Direct Immunofluorescence (IF) showed glomerular deposition of IgA tract with 1+ IgM and Kappa and negative for any complement deposition. Urine protein electrophoresis did not reveal any specific protein spike [Supplementary Table 1].
Table 1: Description of the individual attacks with corresponding imaging findings and investigations

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Figure 1: MR Imaging of Case 1; (a) In 1st attack oval T2 hyperintense lesion in right dorsal pons. (b) During 2nd attack, axial FLAIR image showing hyperintensity in dorsal pons. (c) In same attack showing axial DWI showing diffusion restriction in the bilateral corticospinal tract. (d and e) During 3rd attack axial T2WI showing persistent hyperintensity in the periaqueductal area (d) and new lesions in the left middle cerebellar peduncles (e). (f and g) Sagittal T2WI of spine showing hyperintense skip lesions in dorsal pons, opposite C4 to C6 cervical cord (f) opposite D2 and D7 to D11 vertebrae (g)

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CASE 2: A 28-year-old right-handed gentleman was diagnosed with a case of beta thalassemia major at 1.5 years of age and was transfusion dependent. Seven years back, he was started on chelation therapy with deferasirox and thalidomide. He experienced two attacks of the neurological deficit over a period of 1.5 years with incomplete recovery in between the episodes. Details of the clinical events with imaging and investigations are given in [Table 1] and [Figure 2]. The patient was diagnosed as a case of tumefactive MOGAD in a case of beta thalassemia major is an entity not described previously [Supplementary Table 1].
Figure 2: MRI of CASE 2 (a) During 1st attack T2WI showing hyperintensity in the right thalamoganglionic and posterior limb of internal capsule. (b) and (f and g) After 2nd attack, MRI spine showing diffuse and hypointense marrow signals in the vertebral body and posterior elements. Intramedullary cord signal hyperintensities opposite C2 C3 (g) and D2 to D5, (b) vertebral bodies with predominantly central and left hemicord involvement (f). (c-e) FLAIR, DWI, and T1C images, respectively, after the second attack showing hyperintensity and expansion of the right capsulo-ganglionic, thalamic region with extension into the right insula, operculum, inferior extension into the right cerebral peduncle, right side of midbrain, pons, right superior and middle cerebellar peduncles laterally extending to the adjoining frontotemporal lobes, optic tract and optic radiation, with peripheral areas of restricted diffusion, surrounding edema, and significant mass effect. Patchy peripheral contrast enhancement. (h-j) 6 months post immunosuppression shows regression of all the lesions with residual atrophic changes

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We have described here two unique cases of systemic involvement in MOGAD. MOG is a minor component of the CNS myelin sheath, comprising less than 0.5% but many of its epitopes have been demonstrated to be highly immunogenic.[2] MOG Ab titers with a high sensitivity and specificity in serum live cell-based assays, may exert additional properties outside of the CNS, supported early on by the predominance of Ab against MOG in the serum. At the same time, their intrathecal production appears to be rare.[3] In Case 1, there was asymptomatic proteinuria with kidney biopsy showing podocyte abnormality and immunoglobulin deposits. We can postulate that apart from CNS involvement, MOG antibodies are polyreactive and have implications for systemic autoimmunity. Peterson et al.[4] 2007 demonstrated that, in animal models, after inoculation of MOG 92–106 antibodies producing hybridoma cell lines, there was significant binding in different organs depending on the variant of antibody and route of administration. Antibody deposition was detected in the glomeruli of the kidney and in the liver of injected mice. Further study by Peterson et al.[5] in 2008 demonstrated that adoptive transfer of hybridoma cells producing MOG 92-106 reactive antibodies into immunocompetent mice also resulted in renal pathology consisting of Ig deposition in the kidney and proteinuria. There was a linear pattern of IgM deposition in the glomeruli suggesting that the antibodies are recognizing intrinsic fixed antigens but no significant cellular proliferation. Proteinuria was detected in mice at 5 weeks post-injection, and by 6 weeks had significantly more protein in their urine compared to the control. In our patient also similar linear patterns were demonstrated without any complement deposition, any glomerular or tubular injury apart from the affection of the podocytes which when combined with the absence of hematuria clinically rules out other possibilities of classical IgA nephropathy. On the other hand, an association between SLE or primary Sjogren's disease and coexisting MOG seropositivity has been demonstrated in a few case reports.[6],[7] It may result in either tubulointerstitial nephritis or an immune complex-mediated glomerulopathy.[8]

Currently, various reports with increasing evidence associate β-thalassemia trait with autoimmune conditions, nephritis, diabetes, arthritis, fibromyalgia, and asthma are reported. TRIM21, STIM1, and Orai proteins, CD 151 encoding membrane tetraspanin PETA 3, TC 21, IL1R-related proteins, and many others have chromosome 11p locus in proximity to β globin gene and may contribute to the autoimmune association.[9] Especially genetic association between SLE and Sjogren's syndrome is a well-postulated hypothesis.[10] Association of multiple sclerosis in β thalassemia has been demonstrated in few studies. Nomovi et al.[11] studied 863 MS patients among whom 147 (17%) had minor β thalassemia which is higher than the normal population occurrence. Coexistence of β thalassemia and MOG ab disease like in our case is the first of its kind to the best of our knowledge. Whether the two occurrences in the same patient are coincidental or MOG and thalassemia genetically predispose each other remains still to be elucidated. In view of the previously discussed immunoregulatory genes, sharing a common chromosomal locus with the β globin chain may be a gateway for establishing further association between the two.

Both our patients had atypical systemic features associated with the recurrent relapsing course of the MOGAD. There is immense scope for further large-scale research as well as careful evaluation of the affected patients to further strengthen our postulations for future development.

Informed consent

Informed consent was obtained from the patient included in the study.

No personal or medical information about identifiable individual is included in the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Denève M, Biotti D, Patsoura S, Ferrier M, Meluchova Z, Mahieu L, et al. MRI features of demyelinating disease associated with anti-MOG antibodies in adults. J Neuroradiol 2019;46:312–8.  Back to cited text no. 1
    
2.
Dos Passos GR, Oliveira LM, da Costa BK, Apostolos-Pereira SL, Callegaro D, Fujihara K, et al. MOG-IgG-associated optic neuritis, encephalitis, and myelitis: Lessons learned from neuromyelitis optica spectrum disorder. Front Neurol 2018;9:217.  Back to cited text no. 2
    
3.
Soiza RL, Donaldson AIC, Myint PK. Vaccine against arteriosclerosis: An update. Ther Adv Vaccines 2018;9:259–61.  Back to cited text no. 3
    
4.
Peterson LK, Tsunoda I, Masaki T, Fujinami RS. Polyreactive myelin oligodendrocyte glycoprotein antibodies: Implications for systemic autoimmunity in progressive experimental autoimmune encephalomyelitis. J Neuroimmunol 2007;183:69–80.  Back to cited text no. 4
    
5.
Peterson LK, Masaki T, Wheelwright SR, Tsunoda I, Fujinami RS. Cross-reactive myelin antibody induces renal pathology. Autoimmunity 2008;41:526–36.  Back to cited text no. 5
    
6.
Jobling K, Ledingham D, Ng W-F, Guadagno J. Positive anti-MOG antibodies in a patient with Sjögren's syndrome and transverse myelitis. Eur J Rheumatol 2019;6:100–2.  Back to cited text no. 6
    
7.
Caroline Breis L, Antônio Machado Schlindwein M, Pastor Bandeira I, Machiavelli Fontana T, Fiuza Parolin L, Weingrill P, et al. MOG-IgG-associated disorder and systemic lupus erythematosus disease: Systematic review. Lupus 2021;30:385–92.  Back to cited text no. 7
    
8.
Evans R, Zdebik A, Ciurtin C, Walsh SB. Renal involvement in primary Sjögren's syndrome. Rheumatology (Oxford)2015;54:1541–8.  Back to cited text no. 8
    
9.
Altinoz MA, Gedikoglu G, Deniz G. β-Thalassemia trait association with autoimmune diseases: β-globin locus proximity to the immunity genes or role of hemorphins? Immunopharmacol Immunotoxicol 2012;34:181–90.  Back to cited text no. 9
    
10.
Castellino G, Govoni M, Padovan M, Rizzo N, Trotta F. Beta thalassaemic trait and systemic lupus erythematosus. Ann Rheum Dis 2005;64:653–4.  Back to cited text no. 10
    
11.
Nomovi M, Dorche MS, Nikseresht A. Prevalence of minor beta thalassemia (MBT) in patients with multiple sclerosis (MS) in Southern Iran. Mult Scler Relat Disord 2020;37:101528.  Back to cited text no. 11
    


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