Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Mar 27;16(1):80.
doi: 10.1186/s12967-018-1450-6.

HLA alleles modulate EBV viral load in multiple sclerosis

Simone Agostini  1 , Roberta Mancuso  2 , Franca R Guerini  2 , Sandra D'Alfonso  3 , Cristina Agliardi  2 , Ambra Hernis  2 , Milena Zanzottera  2 , Nadia Barizzone  3 , Maurizio A Leone  4 , Domenico Caputo  2 , Marco Rovaris  2 , Mario Clerici  2   5
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.

PubMed Disclaimer

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
See this image and copyright information in PMC

References

    1. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372:1502–1517. doi: 10.1016/S0140-6736(08)61620-7. - DOI - PubMed
    1. GAMES; Transatlantic multiple sclerosis genetics cooperative A meta-analysis of whole genome linkage screens in multiple sclerosis. J Neuroimmunol. 2003;143:39–46. doi: 10.1016/j.jneuroim.2003.08.009. - DOI - PubMed
    1. Jersild C, Svejgaard A, Fog T. HL-A antigens and multiple sclerosis. Lancet. 1972;1:1240–1241. doi: 10.1016/S0140-6736(72)90962-2. - DOI - PubMed
    1. Nolan D, Castley M, Tschochner M, James I, Qiu W, Sayer D, et al. Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk. Neurology. 2012;79:538–546. doi: 10.1212/WNL.0b013e318263c407. - DOI - PubMed
    1. Zivadinov R, Uxa L, Zacchi T, Nasuelli D, Ukmar M, Furlan C, et al. HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis. J Neurol. 2003;250:1099–1106. doi: 10.1007/s00415-003-0164-7. - DOI - PubMed

Publication types