Anti-Myelin Oligodendrocyte Glycoprotein and Human Leukocyte Antigens as Markers in Pediatric and Adolescent Multiple Sclerosis: on Diagnosis, Clinical Phenotypes, and Therapeutic Responses.

Maria P. Gontika,Maria C. Anagnostouli

doi:10.1155/2018/8487471

Abstract

Early-onset (pediatric and adolescent) multiple sclerosis (MS) is a well-established demyelinating disease that accounts for approximately 3-5% of all MS cases. Thus, identifying potential biomarkers that can reflect the pathogenic mechanisms, disease course and prognosis, and therapeutic response in such patients is of paramount importance. Myelin oligodendrocyte glycoprotein (MOG) has been regarded as a putative autoantigen and autoantibody target in patients with demyelinating diseases for almost three decades. However, recent studies have suggested that antibodies against MOG represent a distinct clinical entity of dominantly humoral profile, with a range of clinical phenotypes closely related to the age of onset, specific patterns of disease course, and responses to treatment. Furthermore, the major histocompatibility complex (MHC)—which has been regarded as the “gold standard” for attributing genetic burden in adult MS since the early 1970s—has also emerged as the primary genetic locus in early-onset MS, particularly with regard to the human leukocyte antigen (HLA) alleles DRB1⁎1501 and DRB1⁎0401. Recent studies have investigated the potential interactions among HLA, MOG, and environmental factors, demonstrating that early-onset MS is characterized by genetic, immunogenetic, immunological, and familial trait correlations. In this paper, we review recent evidence regarding HLA-genotyping and MOG antibodies—the two most important candidate biomarkers for early-onset MS—as well as their potential application in the diagnosis and treatment of MS.

Highlights

Multiple sclerosis (MS) is a chronic autoimmune demyelinating and neurodegenerative disease of the central nervous system (CNS), representing the most common cause of neurological disability among young adults
We review recent evidence regarding human leukocyte antigen (HLA) genotyping and myelin oligodendrocyte glycoprotein (MOG) antibodies—the two most important candidate biomarkers for early-onset MS—as
HLADRB1∗0401, which appears to correlate with younger age at onset via epistatic interactions with HLA-DRB1∗1501, appears to bind with high affinity to MOG epitopes in both familial patients with MS and asymptomatic relatives. These findings indicate that humoral immune reactivity against MOG is partially under the control of certain HLA class II alleles [102,103,104,105,106,107]. This observation may be helpful in guiding therapy, as the HLA-DRB1∗0401 allele is associated with a greater risk of developing neutralizing antibodies against interferon beta (IFN-β), which have been linked to poor therapeutic outcomes in adults [108]

Summary

Introduction

Multiple sclerosis (MS) is a chronic autoimmune demyelinating and neurodegenerative disease of the central nervous system (CNS), representing the most common cause of neurological disability among young adults. The pediatric and adolescent form of the disease constituted a controversial entity that often escaped diagnosis. Early-onset (pediatric and adolescent) MS is a wellestablished demyelinating disease that accounts for approximately 3-5% of all MS cases [1,2,3]. Identifying potential biomarkers that can reflect the pathogenic mechanisms, disease course and prognosis, and therapeutic response is of paramount importance. We review recent evidence regarding human leukocyte antigen (HLA) genotyping and myelin oligodendrocyte glycoprotein (MOG) antibodies—the two most important candidate biomarkers for early-onset MS—as. Multiple Sclerosis International well as their potential application in the diagnosis and treatment of MS

MOG Antibody-Related Disorders

Findings

Discussion

Conclusions