HLA alleles modulate EBV viral load in multiple sclerosis

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 patho...

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Published inJournal of translational medicine Vol. 16; no. 1; p. 80
Main Authors Agostini, Simone, Mancuso, Roberta, Guerini, Franca R, D'Alfonso, Sandra, Agliardi, Cristina, Hernis, Ambra, Zanzottera, Milena, Barizzone, Nadia, Leone, Maurizio A, Caputo, Domenico, Rovaris, Marco, Clerici, Mario
Format Journal Article
LanguageEnglish
Published England BioMed Central 27.03.2018
BMC
Subjects
Adult
Alleles
Case-Control Studies
Cytomegalovirus - physiology
Epstein-Barr virus
Female
Genotype
Herpesvirus 4, Human - physiology
HLA Antigens - genetics
HLA-A02
HLA-B07
HLA-class I alleles
Humans
Immunogenetics
Male
Middle Aged
Multiple sclerosis
Multiple Sclerosis - blood
Multiple Sclerosis - genetics
Multiple Sclerosis - virology
Seroepidemiologic Studies
Viral Load
HLA-A02
Immunogenetics
Multiple sclerosis
Epstein-Barr virus
HLA-B07
HLA-class I alleles
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Abstract 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. 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). 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. 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.
AbstractList 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. 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). 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. 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.
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.
BACKGROUNDThe 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.METHODSHLA 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).RESULTSSignificantly 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.CONCLUSIONSHost 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.
ArticleNumber 80
Author Zanzottera, Milena
Agostini, Simone
Guerini, Franca R
Mancuso, Roberta
Agliardi, Cristina
Barizzone, Nadia
D'Alfonso, Sandra
Caputo, Domenico
Rovaris, Marco
Hernis, Ambra
Clerici, Mario
Leone, Maurizio A
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Issue 1
Keywords HLA-A02
Immunogenetics
Multiple sclerosis
Epstein-Barr virus
HLA-B07
HLA-class I alleles
Language English
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Snippet The etiopathology of multiple sclerosis (MS) is believed to include genetic and environmental factors. Human leukocyte antigen (HLA) alleles, in particular,...
BACKGROUNDThe etiopathology of multiple sclerosis (MS) is believed to include genetic and environmental factors. Human leukocyte antigen (HLA) alleles, in...
Abstract Background The etiopathology of multiple sclerosis (MS) is believed to include genetic and environmental factors. Human leukocyte antigen (HLA)...
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StartPage 80
SubjectTerms Adult
Alleles
Case-Control Studies
Cytomegalovirus - physiology
Epstein-Barr virus
Female
Genotype
Herpesvirus 4, Human - physiology
HLA Antigens - genetics
HLA-A02
HLA-B07
HLA-class I alleles
Humans
Immunogenetics
Male
Middle Aged
Multiple sclerosis
Multiple Sclerosis - blood
Multiple Sclerosis - genetics
Multiple Sclerosis - virology
Seroepidemiologic Studies
Viral Load
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Title HLA alleles modulate EBV viral load in multiple sclerosis
URI https://www.ncbi.nlm.nih.gov/pubmed/29587799
https://search.proquest.com/docview/2019484553
https://pubmed.ncbi.nlm.nih.gov/PMC5870171
https://doaj.org/article/d9e65d7e095f4da3b9a05365e4c77552
Volume 16
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