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BRIEF COMMUNICATIONS: Susanne Gaertner, Katrien L. de Graaf, Bernhard Greve, and Robert Weissert Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis Neurology 2004; 63: 2381-2383 [Abstract] [Full text] [PDF]

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Reply to Lolli et al

Robert Weissert   (28 March 2005)

Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis

Francesco Lolli, Paolo Rovero, Mario Chelli, and Anna Maria Papini   (28 March 2005)

Reply to Lolli et al 28 March 2005
Robert Weissert, Department of General Neurology, Hertie Institute for Clinical Brain Research, Univ. of Tuebingen Hopp-Seyler-Strasse 3, 72076 Tuebingen, Germany Send Correspondence to journal: Re: Reply to Lolli et al robert.weissert{at}uni-tuebingen.de Robert Weissert	Lolli et al support our findings regarding the importance of posttranslational modifications and native conformation in the antigen preparation used for probing of myelin-oligodendrocyte- glycoprotein (MOG)- specific antibodies in patients with multiple sclerosis (MS). [1] Regarding the current developments of test assays for MS [6,7], several issues should be considered. First it is unclear if antibodies are relevant in disease pathogenesis or maintenance in MS or if they are just an epiphenomenon even though we know that anti-myelin-oligodendrocyte-glycoprotein (MOG) antibodies are pathogenic in certain animal models of MS. [8] There is emerging data that antibodies are useful for diagnosis of MS and MS subtypes [1,9,10]. In addition, it is important to define the antigens and epitopes for probing antibody responses. Third, there are different test systems for detection of antibodies including: western blotting, ELISA, RIA and FACS. All have certain advantages and disadvantages and differ in their sensitivity and specificity to detect relevant (auto)antibodies. The combined efforts of several laboratories are necessary. The outcome of such studies will be the declaration of the best suited test methods and the best suited (auto)antigens. Patients with MS will benefit in regard to early diagnosis, prognosis, therapy selection and monitoring. References 6. Hershman T. Israeli researchers eye simple test for multiple sclerosis. Nat Med 2004;10:1147. 7. Papini AM. Simple test for multiple sclerosis. Nat Med 2005;11:13. 8. Linington C, Lassmann H. Antibody responses in chronic relapsing experimental allergic encephalomyelitis: correlation of serum demyelinating activity with antibody titre to the myelin/oligodendrocyte glycoprotein (MOG). J Neuroimmunol 1987;17:61-69. 9. Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 2003;349:139- 145. 10. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106-2112.
Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis 28 March 2005
Francesco Lolli, Dipartimento di Scienze Neurologiche e Psichiatriche , Università degli studi di Firenze viale Pieraccini 6, 50134 Firenze, Italy, Paolo Rovero, Mario Chelli, and Anna Maria Papini Send Correspondence to journal: Re: Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis lolli{at}unifi.it Francesco Lolli, et al.	Gaertner et al recently reported an elevation of serum antibodies against a recombinant mammalian glycosylated MOG in multiple sclerosis (MS). [1] The results emphasize that anti-MOG autoimmunity may be important in monitoring MS. The authors also discuss that the “native” MOG conformation and glycosylation deserve further study and characterization. Although the role of native glycosylation and post-translational modifications are better characterized in many autoimmune diseases, they potently affect the processing and tolerance to autoantigens in many autoimmune diseases. [2] We used a molecular approach to study anti-MOG autoantibody recognition of glycosylated epitopes. Employing synthetic glycopeptides of hMOG(30-50) containing a glucosyl moiety on the side chains of Asn, Ser or Hyp at position 31, the native site of MOG glycosylation, anti-hMOG(30-50) antibodies were detected only using the glycopeptide [Asn31(Glc)]hMOG(30-50). [3] The glycopeptide of the immunodominant region of MOG, hMOG(30-50), containing a b-D-glucopyranosyl residue linked to the native site glycosylation, Asn-31, detected MS specific antibodies that correlated with the MS inflammatory activity as revealed by MRI. [4] In further studies of glycopeptide by NMR analysis, we also found that the glycopeptide antibody recognition in MS is most likely driven by direct interactions of the antibody binding site with the Asn-linked sugar moiety, implying a conformation dependent recognition. [5] Globally, our results confirm the role of glycosylation as well as conformation in recognition and binding of MS autoantibodies, such as anti-MOG antibodies. References 1. Gaertner S, de Graaf KL, Greve B, Weissert R. Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis. Neurology 2004; 63:2381-2383. 2. Doyle HA, Mamula MJ. Post-translational protein modifications in antigen recognition and autoimmunity. Trends Immunol 2001; 22:443-449. 3. Mazzucco S, Mata S, Vergelli M et al. A synthetic glycopeptide of human myelin oligodendrocyte glycoprotein to detect antibody responses in multiple sclerosis and other neurological diseases. Bioorg Med Chem Lett 1999; 9:167-172. 4. Papini A, Mazzucco S, Fioresi R et al. [Asn31(N-D-Glucopyranosyl)]hMOG(30-50) an antigen to identify anti-MOG peptide antibodies in multiple sclerosis patients. In: 10th International Congress of Immunology, New Delhi, India 1-6, 1998. Talwar GP, Nath I, Ganguly NK, Rao KSV eds. Bologna: Monduzzi editore, 1998; 1239-1244. 5. Carotenuto A, D'Ursi AM, Nardi E, Papini AM, Rovero P. Conformational analysis of a glycosylated human myelin oligodendrocyte glycoprotein peptide epitope able to detect antibody response in multiple sclerosis. J Med Chem 2001; 44:2378-2381. Disclosures The study was supported in part by C.S.F. srl, viale Petrarca 6, Firenze, Italy. A patent named "Glycopeptides, their preparation and use in the diagnosis of therapeutic treatment in multiple sclerosis", PCT number 2003 WO 03/000733 A2, inventors Annamaria Papini, Mario Chelli, Paolo Rovero and Francesco Lolli, is owned by the University of Florence and licensed to C.S.F. srl, Firenze, Italy.