Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis.
OBJECTIVE
To determine the role of gene-environmental interactions between the Class I and Class II HLA alleles and the humoral anti-Epstein-Barr Virus (EBV) responses in the development of brain injury and clinical disability in multiple sclerosis (MS) patients.


METHODS
A total of 93 MS patients (62 females; 31 males) and 122 healthy controls underwent HLA typing and testing for antibodies against EBV. The MS patients underwent brain MRI and quantitative measurements of T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF) were obtained. There were 54 MS cases that underwent MRI and EBV-antibody assessments at the 3-year follow-up. The anti-EBV panel included measurements of the levels of anti-EBV early antigen (EA) IgG, anti-EBV nuclear antigen (EBNA) IgG and anti-EBV viral capsid antigen (VCA) IgM and anti-EBV VCA IgG. The relationships between HLA alleles, anti-EBV antibody levels, MRI and clinical parameters were assessed in regression analysis.


RESULTS
The presence of HLA B7 was associated with increased T1-LV and trends indicating increased anti-EBV VCA IgG levels, higher disability (EDSS) and more destructive MRI parameters (increased T2-LV and decreased BPF). The presence of HLA A2 was associated with lower EDSS and a trend toward decreased anti-EBV VCA IgG levels; the associations with MRI variables were not significant. The HLA B7-A2 haplotype was significantly associated with higher T2-LV and T1-LV and a trend toward lower BPF was observed.


CONCLUSIONS
Our data suggest that gene-environment interactions between specific HLA Class I loci and EBV exposure are associated with MRI markers of lesion injury and brain atrophy in MS patients.
Zivadinov
Robert
R
Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, USA.
Weinstock-Guttman
Bianca
B
Zorzon
Marino
M
Uxa
Laura
L
Serafin
Maurizia
M
Bosco
Antonio
A
Bratina
Alessio
A
Maggiore
Cosimo
C
Grop
Attilio
A
Tommasi
Maria Antonietta
MA
Srinivasaraghavan
Bhooma
B
Ramanathan
Murali
M
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001921:Brain / Q000276:immunology / Q000473:pathology* / Q000821:virology; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D015793:HLA-B7 Antigen / Q000235:genetics* / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000821:virology; D012720:Severity of Illness Index
D000914:Antibodies, Viral; D015415:Biomarkers; D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen; D007074:Immunoglobulin G