PMID- 23886832
OWN - NLM
STAT- MEDLINE
DCOM- 20141030
LR  - 20140304
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 20
IP  - 3
DP  - 2014 Mar
TI  - Combining HLA-DR risk alleles and anti-Epstein-Barr virus antibody profiles to 
      stratify multiple sclerosis risk.
PG  - 286-94
LID - 10.1177/1352458513498829 [doi]
AB  - BACKGROUND: Risk factors for multiple sclerosis (MS) include human leukocyte 
      antigen (HLA)-DR and Epstein-Barr virus (EBV)-specific antibody responses, 
      including an epitope within EBV nuclear antigen 1 (EBNA-1) that is of recent 
      interest. OBJECTIVE: The objective of this paper is to assess case-control 
      associations between MS risk and anti-EBV antibody levels as well as HLA-DR 
      profiles, gender and age in a population-based cohort. METHODS: Serological 
      responses to EBV were measured in 426 MS patients and 186 healthy controls. 
      HLA-DR typing was performed using sequence-based methods. RESULTS: MS patients 
      had significantly higher levels of antibodies against epitope-specific and 
      polyspecific EBNA-1 and viral capsid antigen (VCA), compared with controls (all p 
      < 10(-15)). In regression analyses, anti-EBNA-1 and anti-VCA antibody levels, 
      protective HLA-DR*04/07/09 alleles and gender (all p < 0.003) contributed 
      independently to a model that classified cases and controls with an odds ratio > 
      20 (sensitivity 92%, specificity 64%). Notably, the strong influence of high-risk 
      HLA-DR alleles was abrogated after inclusion of EBV serology results. 
      CONCLUSIONS: The ability to discriminate MS cases and controls can be 
      substantially enhanced by including anti-EBV serology as well as HLA-DR risk 
      profiles. These findings support the relevance of EBV-specific immunity in MS 
      pathogenesis, and implicate both HLA-dependent and HLA-independent immune 
      responses against EBNA-1 as prominent disease risk factors.
FAU - Strautins, K
AU  - Strautins K
AD  - Institute for Immunology & Infectious Diseases, Murdoch University, Australia.
FAU - Tschochner, M
AU  - Tschochner M
FAU - James, I
AU  - James I
FAU - Choo, L
AU  - Choo L
FAU - Dunn, D S
AU  - Dunn DS
FAU - Pedrini, M
AU  - Pedrini M
FAU - Kermode, A
AU  - Kermode A
FAU - Carroll, W
AU  - Carroll W
FAU - Nolan, D
AU  - Nolan D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130725
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (Antibodies, Viral)
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Antibodies, Viral/*immunology
MH  - Case-Control Studies
MH  - Epstein-Barr Virus Nuclear Antigens/*immunology
MH  - Female
MH  - HLA-DR Antigens/*genetics
MH  - Herpesvirus 4, Human/*immunology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*etiology/genetics/immunology
MH  - Risk Factors
MH  - Sex Factors
MH  - Young Adult
OTO - NOTNLM
OT  - EBV
OT  - ELISA
OT  - HLA
OT  - Multiple sclerosis
OT  - genetics
OT  - immunology
EDAT- 2013/07/28 06:00
MHDA- 2014/10/31 06:00
CRDT- 2013/07/27 06:00
PHST- 2013/07/27 06:00 [entrez]
PHST- 2013/07/28 06:00 [pubmed]
PHST- 2014/10/31 06:00 [medline]
AID - 1352458513498829 [pii]
AID - 10.1177/1352458513498829 [doi]
PST - ppublish
SO  - Mult Scler. 2014 Mar;20(3):286-94. doi: 10.1177/1352458513498829. Epub 2013 Jul 
      25.