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. 2018 Mar 27;16(1):80.
doi: 10.1186/s12967-018-1450-6.

HLA alleles modulate EBV viral load in multiple sclerosis

Affiliations

HLA alleles modulate EBV viral load in multiple sclerosis

Simone Agostini et al. J Transl Med. .

Abstract

Background: The etiopathology of multiple sclerosis (MS) is believed to include genetic and environmental factors. Human leukocyte antigen (HLA) alleles, in particular, are associated with disease susceptibility, whereas Epstein Barr Virus (EBV) infection has long been suspected to play a role in disease pathogenesis. The aim of the present study is to evaluate correlations between HLA alleles and EBV infection in MS.

Methods: HLA alleles, EBV viral load (VL) and serum anti-EBV antibody titers were evaluated in EBV-seropositive MS patients (N = 117) and age- and sex-matched healthy controls (HC; N = 89).

Results: Significantly higher DNA viral loads (p = 0.048) and EBNA-1 antibody titer (p = 0.0004) were seen in MS compared to HC. EBV VL was higher in HLA-B*07+ (p = 0.02) and HLA-DRB1*15+ (p = 0.02) MS patients, whereas it was lower in HLA-A*02+ (p = 0.04) subjects. EBV VL was highest in HLA-A*02-/B*07+/DRB1*15+ patients and lowest in HLA-A*A02+/B*07-/DRB1*15- individuals (p < 0.0001). HLA-B*07 resulted the most associated allele to EBV VL after multiple regression analysis considering altogether the three alleles, (p = 0.0001). No differences were observed in anti-EBV antibody titers in relationship with HLA distribution.

Conclusions: Host HLA-B*07 allele influence EBV VL in MS. As HLA-class I molecules present antigens to T lymphocytes and initiate immune response against viruses, these results could support a role for EBV in MS.

Keywords: Epstein-Barr virus; HLA-A*02; HLA-B*07; HLA-class I alleles; Immunogenetics; Multiple sclerosis.

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Figures

Fig. 1
Fig. 1
EBV viral load in blood of multiple sclerosis patients and healthy controls
Fig. 2
Fig. 2
EBV viral load in blood of multiple sclerosis patients (a) and healthy controls (b) carrying HLA-B*07 allele
Fig. 3
Fig. 3
EBV viral load in blood of multiple sclerosis patients (a) and healthy controls (b) carrying HLA-DRB1*15 (c) allele
Fig. 4
Fig. 4
EBV viral load in blood of multiple sclerosis patients (a) and healthy controls (b) carrying HLA-A*02. Black dots represent subjects carrying HLA-B*07 allele
Fig. 5
Fig. 5
EBV viral load in blood of multiple sclerosis patients (a) and of healthy controls (b) in relationship with the co-segregation of HLA-A*02, -B*07 and -DRB1*15 alleles
Fig. 6
Fig. 6
EBV viral load in blood of RR-MS (a) and P-MS (b) carrying HLA-A*02, -B*07 and -DRB1*15 alleles

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