Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in ‘pattern II multiple sclerosis’ and brain biopsy findings in a MOG-IgG-positive case

First Published February 11, 2016 Research Article Find in PubMed

Authors

Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany
by this author
,
Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany
by this author
,
Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany
by this author
,
Department of Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany
by this author
,
Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
by this author
,
Department of Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany; NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Berlin, Germany
by this author
,
Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany
by this author
,
Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany
by this author
...
First Published Online: February 11, 2016

Histopathological studies have revealed four different immunopathological patterns of lesion pathology in early multiple sclerosis (MS). Pattern II MS is characterised by immunoglobulin and complement deposition in addition to T-cell and macrophage infiltration and is more likely to respond to plasma exchange therapy, suggesting a contribution of autoantibodies.

To assess the frequency of anti-myelin oligodendrocyte glycoprotein (MOG), anti-M1-aquaporin-4 (AQP4), anti-M23-AQP4, anti-N-methyl-d-aspartate-type glutamate receptors (NMDAR) and 25 other anti-neural antibodies in pattern II MS.

Thirty-nine serum samples from patients with MS who had undergone brain biopsy (n = 24; including 13 from patients with pattern II MS) and from histopathologically non-classified MS patients (n = 15) were tested for anti-MOG, anti-M1-AQP4, anti-M23-AQP4, anti-NMDAR, anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-type glutamate receptors (AMPAR), anti-gamma-aminobutyric acid receptors (GABABR), anti-leucine-rich, glioma-activated protein 1 (LGI1), anti-contactin-associated protein 2 (CASPR2), anti-dipeptidyl-peptidase-like protein-6 (DPPX), anti-Tr/Delta/notch-like epidermal growth factor–related receptor (DNER), anti-Hu, anti-Yo, anti-Ri, anti-Ma1/Ma2, anti-CV2/collapsin response mediator protein 5 (CRMP5), anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Ca/RhoGTPase-activating protein 26 (ARHGAP26), anti-Sj/inositol-1,4,5-trisphosphate receptor 1 (ITPR1), anti-Homer3, anti-carbonic anhydrase–related protein (CARPVIII), anti-protein kinase gamma (PKCgamma), anti-glutamate receptor delta 2 (GluRdelta2), anti-metabotropic glutamate receptor 1 (mGluR1) and anti-mGluR5, as well as for anti-glial nuclei antibodies (AGNA) and Purkinje cell antibody 2 (PCA2).

Antibodies to MOG belonging to the complement-activating immunoglobulin G1 (IgG1) subclass were detected in a patient with pattern II MS. Detailed brain biopsy findings are shown.

This is the largest study on established anti-neural antibodies performed in MS so far. MOG-IgG may play a role in a small percentage of patients diagnosed with pattern II MS.

1. Lucchinetti, C, Bruck, W, Parisi, J. Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Ann Neurol 2000; 47: 707717.
Google Scholar | Crossref | Medline | ISI
2. Keegan, M, Konig, F, McClelland, R. Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet 2005; 366: 579582.
Google Scholar | Crossref | Medline | ISI
3. Jarius, S, Ruprecht, K, Wildemann, B. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflammation 2012; 9: 14.
Google Scholar | Crossref | Medline | ISI
4. Reindl, M, Di Pauli, F, Rostasy, K. The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 2013; 9: 455461.
Google Scholar | Crossref | Medline | ISI
5. Jarius, S, Wildemann, B, Paul, F. Neuromyelitis optica: Clinical features, immunopathogenesis and treatment. Clin Exp Immunol 2014; 176: 149164.
Google Scholar | Crossref | Medline | ISI
6. Levy, M, Wildemann, B, Jarius, S. Immunopathogenesis of neuromyelitis optica. Adv Immunol 2014; 121: 213242.
Google Scholar | Crossref | Medline | ISI
7. Bruck, W, Popescu, B, Lucchinetti, CF. Neuromyelitis optica lesions may inform multiple sclerosis heterogeneity debate. Ann Neurol 2012; 72: 385394.
Google Scholar | Crossref | Medline | ISI
8. Kuhlmann, T, Lassmann, H, Bruck, W. Diagnosis of inflammatory demyelination in biopsy specimens: A practical approach. Acta Neuropathol 2008; 115: 275287.
Google Scholar | Crossref | Medline | ISI
9. Mader, S, Gredler, V, Schanda, K. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinflammation 2011; 8: 184.
Google Scholar | Crossref | Medline | ISI
10. Titulaer, MJ, Hoftberger, R, Iizuka, T. Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014; 75: 411428.
Google Scholar | Crossref | Medline | ISI
11. Saadoun, S, Waters, P, Owens, GP. Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain. Acta Neuropathol Commun 2014; 2: 35.
Google Scholar | Crossref | Medline | ISI
12. Balint, B, Jarius, S, Nagel, S. Progressive encephalomyelitis with rigidity and myoclonus: A new variant with DPPX antibodies. Neurology 2014; 82: 15211528.
Google Scholar | Crossref | Medline | ISI
13. Stoeck, K, Carstens, PO, Jarius, S. Prednisolone and azathioprine are effective in DPPX antibody–positive autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm 2015; 2: e86.
Google Scholar | Crossref | Medline
14. Jarius, S, Wildemann, B. ‘Medusa head ataxia’: The expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook. J Neuroinflammation 2015; 12: 168.
Google Scholar | Crossref | Medline | ISI
15. Probst, C, Komorowski, L, de Graaff, E. Standardized test for anti-Tr/DNER in patients with paraneoplastic cerebellar degeneration. Neurol Neuroimmunol Neuroinflamm 2015; 2: e68.
Google Scholar | Crossref | Medline
16. Jarius, S, Wandinger, KP, Horn, S. A new Purkinje cell antibody (anti-Ca) associated with subacute cerebellar ataxia: Immunological characterization. J Neuroinflammation 2010; 7: 21.
Google Scholar | Crossref | Medline | ISI
17. Jarius, S, Martinez-Garcia, P, Hernandez, AL. Two new cases of anti-Ca (anti-ARHGAP26/GRAF) autoantibody-associated cerebellar ataxia. J Neuroinflammation 2013; 10: 7.
Google Scholar | Crossref | Medline | ISI
18. Jarius, S, Wildemann, B. ‘Medusa head ataxia’: The expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC. J Neuroinflammation 2015; 12: 167.
Google Scholar | Crossref | Medline | ISI
19. Doss, S, Nümann, A, Ziegler, A. Anti-Ca/anti-ARHGAP26 antibodies associated with cerebellar atrophy and cognitive decline. J Neuroimmunol 2014; 267: 102104.
Google Scholar | Crossref | Medline | ISI
20. Jarius, S, Scharf, M, Begemann, N. Antibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in cerebellar ataxia. J Neuroinflammation 2014; 11: 206.
Google Scholar | Crossref | Medline | ISI
21. Jarius, S, Wildemann, B. ‘Medusa-head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 1: Anti-mGluR1, anti-Homer-3, anti-Sj/ITPR1 and anti-CARP VIII. J Neuroinflammation 2015; 12: 166.
Google Scholar | Crossref | Medline | ISI
22. Jarius, S, Probst, C, Borowski, K. Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci 2010; 291: 5256.
Google Scholar | Crossref | Medline | ISI
23. Jarius, S, Franciotta, D, Bergamaschi, R. NMO-IgG in the diagnosis of neuromyelitis optica. Neurology 2007; 68: 10761077.
Google Scholar | Crossref | Medline | ISI
24. Jarius, S, Franciotta, D, Paul, F. Testing for antibodies to human aquaporin-4 by ELISA: Sensitivity, specificity, and direct comparison with immunohistochemistry. J Neurol Sci 2012; 320: 3237.
Google Scholar | Crossref | Medline | ISI
25. Jarius, S, Paul, F, Franciotta, D. Mechanisms of Disease: Aquaporin-4 antibodies in neuromyelitis optica. Nat Clin Pract Neurol 2008; 4: 202214.
Google Scholar | Crossref | Medline
26. Jarius, S, Wildemann, B. AQP4 antibodies in neuromyelitis optica: Diagnostic and pathogenetic relevance. Nat Rev Neurol 2010; 6: 383392.
Google Scholar | Crossref | Medline | ISI
27. Lucchinetti, CF, Mandler, RN, McGavern, D. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 2002; 125: 14501461.
Google Scholar | Crossref | Medline | ISI
28. Genain, CP, Cannella, B, Hauser, SL. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med 1999; 5: 170175.
Google Scholar | Crossref | Medline | ISI
29. 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: e62.
Google Scholar | Crossref | Medline
30. Kale, N, Pittock, SJ, Lennon, VA. Humoral pattern II multiple sclerosis pathology not associated with neuromyelitis Optica IgG. Arch Neurol 2009; 66: 12981299.
Google Scholar | Crossref | Medline
31. Jarius, S, Wildemann, B. Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: A critical review of the literature. Brain Pathol 2013; 23: 661683.
Google Scholar | Crossref | Medline | ISI
32. Konig, FB, Wildemann, B, Nessler, S. Persistence of immunopathological and radiological traits in multiple sclerosis. Arch Neurol 2008; 65: 15271532.
Google Scholar | Crossref | Medline
33. Spadaro, M, Gerdes, LA, Mayer, MC. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Ann Clin Transl Neurol 2015; 2: 295301.
Google Scholar | Crossref | Medline | ISI
34. Waters, P, Jarius, S, Littleton, E. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol 2008; 65: 913919.
Google Scholar | Crossref | Medline
35. Jarius, S, Wandinger, KP, Borowski, K. Antibodies to CV2/CRMP5 in neuromyelitis optica-like disease: Case report and review of the literature. Clin Neurol Neurosurg 2012; 114: 331335.
Google Scholar | Crossref | Medline | ISI
36. Mayer, MC, Breithaupt, C, Reindl, M. Distinction and temporal stability of conformational epitopes on myelin oligodendrocyte glycoprotein recognized by patients with different inflammatory central nervous system diseases. J Immunol 2013; 191: 35943604.
Google Scholar | Crossref | Medline | ISI
37. Jarius, S, Paul, F, Fechner, K. Aquaporin-4 antibody testing: Direct comparison of M1-AQP4-DNA-transfected cells with leaky scanning versus M23-AQP4-DNA-transfected cells as antigenic substrate. J Neuroinflammation 2014; 11: 129.
Google Scholar | Crossref | Medline | ISI

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