Abstract
Myelin basic protein (MBP) is thought to be one of the key autoantigens in multiple sclerosis (MS) development. A recent study described the association of the single nucleotide polymorphism (SNP) rs12959006, within the MBP gene, with a higher risk of relapse and worse prognosis. We aim at studying potential associations of this SNP to MS in an independent population. Clinical data of the first 5 years of the disease were collected retrospectively from 291 MS confirmed patients. MBP polymorphism rs12959006 was genotyped in all patients. Associations with EDSS, number of relapses and serology for Herpesvirus 6 (HHV-6) and Epstein Barr (EBV) viruses were studied. Lymphocyte activation measured by CD69 expression was also analyzed according to sex and rs12959006 genotype. The rs12959006 polymorphism contributed significantly to a higher number of relapses at 5 years after onset only in male patients (rs12959006∗TT β = 0.74 [0.36–1.09]; p = 7 × 10–5). Titers of anti-HHV6 IgG antibodies showed also a mild association with relapses, both in male and female patients (β = 0.01 [0.01–0.02]; p = 3.7 × 10–8). Both the genetic variation in MBP and HHV-6 infection aid in predicting a higher number of relapses during the first years of MS. The association described in MBP rs12959006∗T is exclusive to male patients.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease affecting the central nervous system (CNS) and is one of the primary neurological causes of physical disability in young adults [1]
myelin basic protein (MBP) is part of the peptide cocktail used for inducing experimental autoimmune encephalomyelitis (EAE) in mice, along with proteolipid protein (PLP) and myelin olygodendrocyte glycoprotein (MOG) [2]
MBP has not been proved to be the key autoantigen in MS, MBP-specific autoreactive T-cells have been found in blood of MS patients at a higher rate than in healthy individuals [3]
Summary
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease affecting the central nervous system (CNS) and is one of the primary neurological causes of physical disability in young adults [1]. The underlying mechanism seems to be an autoimmune response to unidentified antigens in the CNS. One of these proposed antigens is the myelin basic protein (MBP), MBP and Relapse in MS the second most abundant component of the myelin sheath, and a protein that plays an important role in the myelination process. Several studies have focused on finding new markers for MS diagnosis and prognosis that are cost-effective, reliable, easy to implement and as minimally invasive as possible.
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