Association of Epstein–Barr virus infection with multiple sclerosis in India

Abstract

Objectives

Epstein–Barr virus (EBV) seroprevalence is high from early childhood in Indian populations, though multiple sclerosis (MS) is uncommon. The present study aims to evaluate the association of EBV infection with MS in Indian patients.

Method

In this study 140 MS patients and equal number of matched controls were included. Estimation of serum Immunoglobin G (IgG) for EBV Nuclear antigen 1 (EBNA1), viral capsid antigen (EBV-VCA) and early antigen (EB-EA) were obtained by quantitative enzyme linked immunosorbent assay (ELISA). Patients and controls were genotyped for the human leukocyte antigen (HLA) DRB1*1501 allele.

Results

A modest difference was observed for EBNA1 (p = 0.02) and EBV-VCA (p = 0.03) titres in MS patients as compared to healthy controls. There was no association between EBNA1 titres and MS. High EBNA1 titre (> 99.75 U/l) was significantly associated with HLA DRBI*15:01 (OR = 4.92. CI = 1.07–22.57) status in MS patients but not in healthy controls (OR = 1.19, CI = 0.53–2.63).

Conclusion

Evidence for a strong association with remote EBV infection was lacking in this study of Indian patients with MS. Patients who are carriers of HLA DR15 allele may have high EBNA1 titres. These preliminary results need to be reproduced in an independent and larger dataset.

Introduction

Multiple sclerosis is a chronic immune mediated disorder of complex etiology. Both environmental and genetic factors are implicated in disease causation. Studies in patients of Northern American descent show that nearly 99% of adults with MS have been infected with EBV as compared to 94% age matched controls [1]. In pediatric cases, the association between EBV infection and the development of MS is not very clear. In a North American study, 108 (86%) children with MS were seropositive for remote EBV infection, compared with 61 (64%) matched controls [2]. Pohl et al. in their study found a much stronger association with 98.6% of pediatric MS and 72.1% healthy children showing evidence of remote infection with EBV [3]. These data suggest that prior EBV infection may be a prerequisite for the development of disease and that timing of infection may be important. It is not clear whether specific risk factors important for MS in regions of high prevalence are relevant in areas where the disease is less prevalent. The declining risk in migrants from regions of high to low MS prevalence suggests regional differences in the nature of environmental risk factors [4], [5]. Some studies propose that EBV strain variations may alter susceptibility to MS [6], [7] and that geographic differences in MS prevalence may be linked to EBV as a result.

In India the role of environmental agents involved in MS has not been studied in detail. A study of 63 MS cases and matched controls from the Mumbai region has shown a significant association with childhood viral infections and co-existence of other autoimmune disorders [8]. However the specific role of EBV has not been studied in association with MS in India. In the present investigation we sought to determine whether EBV plays a role in MS risk in the Indian population.