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* Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute,
Program in Immunology and
Department of Neurology, Harvard Medical School,
Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, MA 02115,
¶ Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital for Children, Boston, MA 02114;
|| NeuroResource, University College London Institute of Neurology, London, United Kingdom;
# Institute of Neurology, Department of Paediatrics, Division of Neurology, The Hospital for Sick Children, Toronto, Canada;
** Department of Research and Department of Neurology, University Hospital Basel, Basel, Switzerland;
Department of Pediatrics and Pediatric Neurology, Georg- August-University, Goettingen, Germany;
* Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada;
* Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, Canada;
* Children’s Hospital of Alabama, Birmingham, AL 35233;
* Department of Pediatric Neurology, National Pediatric Hospital "Dr. J.P. Garrahan", Buenos Aires, Argentina;
* Diagnostic Immunology Laboratory, Wadsworth Center, New York State Department of Health, Albany, NY 12207;
* Department of Neurology, Strasbourg University, Alsace, France; and
* Department of Neurology, Kazak State Medical University, Almaty, Kazakhstan
Multiple sclerosis (MS) typically manifests in early to mid adulthood, but there is increasing recognition of pediatric-onset MS, aided by improvements in imaging techniques. The immunological mechanisms of disease are largely unexplored in pediatric-onset MS, in part because studies have historically focused on adult-onset disease. We investigated autoantibodies to myelin surface Ags in a large cohort of pediatric MS cases by flow cytometric labeling of transfectants that expressed different myelin proteins. Although Abs to native myelin oligodendrocyte glycoprotein (MOG) were uncommon among adult-onset patients, a subset of pediatric patients had serum Abs that brightly labeled the MOG transfectant. Abs to two other myelin surface Ags were largely absent. Affinity purification of MOG Abs as well as competition of binding with soluble MOG documented their binding specificity. Such affinity purified Abs labeled myelin and glial cells in human CNS white matter as well as myelinated axons in gray matter. The prevalence of such autoantibodies was highest among patients with a very early onset of MS: 38.7% of patients less than 10 years of age at disease onset had MOG Abs, compared with 14.7% of patients in the 10- to 18-year age group. B cell autoimmunity to this myelin surface Ag is therefore most common in patients with a very early onset of MS.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant PO1 AI045757 from the National Institutes of Health (to K.W.W.), Grant RG 4122-A-6 from the National Multiple Sclerosis Society (to K.W.W.), and Grant A B-O from the Wadsworth Foundation (to B.B.).
2 Address correspondence and reprint requests to Dr. Kai W. Wucherpfennig, Dana-Farber Cancer Institute, 44 Binney Street, Room D1410, Boston, MA 02115. E-mail address: Kai_Wucherpfennig{at}dfci.harvard.edu
3 Abbreviations used in this paper: MS, multiple sclerosis; ADEM, acute disseminated encephalomyelitis; CIS, clinically isolated syndrome; CSF, cerebrospinal fluid; MAG, myelin-associated glycoprotein; MFI, mean fluorescence intensity; MOG, myelin oligodendrocyte glycoprotein; NMO, neuromyelitis optica; OMG, oligodendrocyte-myelin glycoprotein; MRI, magnetic resonance imaging; HA, hemagglutinin.
4 The online version of this article contains supplemental material.
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