Abstract

BackgroundMultiple sclerosis (MS) risk, over 10-fold higher in Western than in Asian countries, is associated with elevated IgG antibody titers against Epstein-Barr viral capcid antigen (anti-EBVCA IgG titers). Given the 84% homology of the open reading frame BCRF1 of Epstein-Barr virus (EBV) to human interleukin 10 (hIL-10) and the remarkable Caucasian-vs.-Asian population differences in hIL-10 gene promoter polymorphisms, this strong association of MS risk with anti-EB-VCA IgG titers may be explained by the genetic variations in the hIL-10 gene.MethodsWe evaluated anti-EB-VCA IgG titers in association with a single nucleotide polymorphism (SNP) in the promoter of hIL-10 at position -819 (hIL-10 T-819C) in a cross-sectional survey of 241 Japanese. Anti-EB-VCA IgG titer and its elevation (≥ 1:160) were evaluated, stratified by sex and hIL-10 T-819C genotype.ResultsThe cytosine-allele frequencies at hIL-10 T-819C were 32.9% in women and 30.9% in men. These are consistent with the published reports of Japanese and Chinese, but substantially lower than those of Caucasians (> 70%). In women, the proportion with elevated anti-EB-VCA IgG titers (≥ 1:160) increased appreciably from 53.7% in the T/T genotype group to 66.7% in the T/C group and to 83.3% in the C/C group (P-trend = 0.037). The titers did not differ by the hIL-10 T-819C genotype in men.ConclusionAnti-EB-VCA IgG titers may increase with the number of cytosine alleles at hIL-10 T-819C in women. This observed gender specific association in Japanese warrants further investigation, especially in Western populations with high MS risk.

Highlights

  • Multiple sclerosis (MS) risk, over 10-fold higher in Western than in Asian countries, is associated with elevated IgG antibody titers against Epstein-Barr viral capcid antigen

  • We hypothesize that genetic variations in the host's human interleukin 10 (hIL-10) gene may modulate the host-organism interaction with this ubiquitous virus encoding an hIL-10 mimic

  • IL-10 polymorphism assay and Epstein-Barr virus (EBV) antibody assay DNA was extracted from buffy coat using a QIAamp blood mini kit (Qiagen, Valencia, CA) and the hIL-10 promoter single nucleotide polymorphism (SNP) at position -819 was characterized by the polymerase chain reaction with confronting two-pair primers (PCRCTPP), which does not require restriction enzyme digestion, developed by our laboratory [23]

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Summary

Introduction

Multiple sclerosis (MS) risk, over 10-fold higher in Western than in Asian countries, is associated with elevated IgG antibody titers against Epstein-Barr viral capcid antigen (anti-EBVCA IgG titers). Journal of Autoimmune Diseases 2008, 5:2 http://www.jautoimdis.com/content/5/1/2 promotes cell proliferation and differentiation, and plays some anti-apoptotic function. These biological activities of hIL-10 are advantageous for viruses that infect and persist in B cells. An open reading frame of EBV, BCRF1, shows a strikingly high degree of sequence homology with hIL-10 (84% homology in amino acid sequence) and viral IL-10 shares many of hIL10's biological activities [1] Based on these observations, we hypothesize that genetic variations in the host's hIL-10 gene may modulate the host-organism interaction with this ubiquitous virus encoding an hIL-10 mimic

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