PMID- 26142251
OWN - NLM
STAT- MEDLINE
DCOM- 20160819
LR  - 20220310
IS  - 1095-9157 (Electronic)
IS  - 0896-8411 (Print)
IS  - 0896-8411 (Linking)
VI  - 64
DP  - 2015 Nov
TI  - The immunogenetics of multiple sclerosis: A comprehensive review.
PG  - 13-25
LID - S0896-8411(15)30001-9 [pii]
LID - 10.1016/j.jaut.2015.06.010 [doi]
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous 
      system and common cause of non-traumatic neurological disability in young adults. 
      The likelihood for an individual to develop MS is strongly influenced by her or 
      his ethnic background and family history of disease, suggesting that genetic 
      susceptibility is a key determinant of risk. Over 100 loci have been firmly 
      associated with susceptibility, whereas the main signal genome-wide maps to the 
      class II region of the human leukocyte antigen (HLA) gene cluster and explains up 
      to 10.5% of the genetic variance underlying risk. HLA-DRB1*15:01 has the 
      strongest effect with an average odds ratio of 3.08. However, complex allelic 
      hierarchical lineages, cis/trans haplotypic effects, and independent protective 
      signals in the class I region of the locus have been described as well. Despite 
      the remarkable molecular dissection of the HLA region in MS, further studies are 
      needed to generate unifying models to account for the role of the MHC in disease 
      pathogenesis. Driven by the discovery of combinatorial associations of 
      Killer-cell Immunoglobulin-like Receptor (KIR) and HLA alleles with infectious, 
      autoimmune diseases, transplantation outcome and pregnancy, multi-locus 
      immunogenomic research is now thriving. Central to immunity and critically 
      important for human health, KIR molecules and their HLA ligands are encoded by 
      complex genetic systems with extraordinarily high levels of sequence and 
      structural variation and complex expression patterns. However, studies to-date of 
      KIR in MS have been few and limited to very low resolution genotyping. 
      Application of modern sequencing methodologies coupled with state of the art 
      bioinformatics and analytical approaches will permit us to fully appreciate the 
      impact of HLA and KIR variation in MS.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Hollenbach, Jill A
AU  - Hollenbach JA
AD  - Department of Neurology, University of California San Francisco, San Francisco, 
      CA 94158, USA. Electronic address: jill.hollenbach@ucsf.edu.
FAU - Oksenberg, Jorge R
AU  - Oksenberg JR
AD  - Department of Neurology, University of California San Francisco, San Francisco, 
      CA 94158, USA.
LA  - eng
GR  - R01 GM109030/GM/NIGMS NIH HHS/United States
GR  - R01 NS076492/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150702
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - HLA Antigens/genetics/immunology
MH  - Humans
MH  - *Immunogenetics
MH  - Multiple Sclerosis/epidemiology/*genetics/*immunology
PMC - PMC4687745
MID - NIHMS709322
OTO - NOTNLM
OT  - Genetics
OT  - Human leukocyte antigen
OT  - Killer-cell immunoglobulin-like receptor
OT  - Multiple sclerosis
EDAT- 2015/07/05 06:00
MHDA- 2016/08/20 06:00
PMCR- 2016/11/01
CRDT- 2015/07/05 06:00
PHST- 2015/06/19 00:00 [received]
PHST- 2015/06/23 00:00 [accepted]
PHST- 2015/07/05 06:00 [entrez]
PHST- 2015/07/05 06:00 [pubmed]
PHST- 2016/08/20 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - S0896-8411(15)30001-9 [pii]
AID - 10.1016/j.jaut.2015.06.010 [doi]
PST - ppublish
SO  - J Autoimmun. 2015 Nov;64:13-25. doi: 10.1016/j.jaut.2015.06.010. Epub 2015 Jul 2.