Elevated Intrathecal Myelin Oligodendrocyte Glycoprotein Antibodies in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a demyelinating neurologic disorder of the central nervous system (CNS) with a hypothesized autoimmune origin and a clinical course that is often unpredictable at disease onset.¹ Discovering a pathologic biomarker to help accurately make the MS diagnosis or predict disease activity and progression would be useful. Humoral immunity may play a role in MS pathogenesis as suggested by cerebrospinal fluid (CSF) oligoclonal IgG² and by the presence of antibodies and complement in association with myelin damage in MS plaques.^3,4 Various antigens have been proposed as targets of the autoantibody response.^5,6 Myelin oligodendrocyte glycoprotein (MOG) is 1 candidate target self-antigen. This protein is a small component of myelin exclusive to the CNS located on the outer surface of the myelin sheath and hence accessible to antibody attack.^7,8 Myelin oligodendrocyte glycoprotein is used to induce experimental autoimmune encephalomyelitis in many species.^9,10 Although anti-MOG antibodies alone cannot induce experimental autoimmune encephalomyelitis, they enhance demyelination in some rodent and primate experimental autoimmune encephalomyelitis models.^10,11 In humans, the pathogenic role of anti-MOG antibodies is less clear. The potential of anti-MOG antibodies as diagnostic and/or prognostic biomarkers is also unknown. Myelin oligodendrocyte glycoprotein–specific antibodies and T cells are present in healthy control individuals and patients with MS,¹² suggesting that the presence of serum anti-MOG antibodies will not be useful to diagnose MS. However, the level and specific target of serum antibodies to MOG may be important.^13-18 For example, serum autoantibodies that targeted extracellular MOG in its native conformation were shown to be lytic in vitro, supporting a potential pathogenic role of these antibodies in MS.¹⁹ Controversy surrounds whether serum antibodies against recombinant MOG (rMOG) may predict a second MS relapse in patients with clinically isolated syndrome (CIS).^20-25 Some of the contradictory evidence to date is likely the result of methodologic differences among studies. In another CIS study, antimyelin antibodies were associated with intrathecal IgG production, CSF pleocytosis, and T2 lesion load.²⁶ Other studies suggest that MOG antibody levels are elevated in the CSF of patients with MS compared with controls with noninflammatory neurologic disease.^27,28