PMID- 19630074
OWN - NLM
STAT- MEDLINE
DCOM- 20090812
LR  - 20171116
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Linking)
VI  - 65
IP  - 6
DP  - 2009 Jun
TI  - Killer immunoglobulin-like receptor ligand HLA-Bw4 protects against multiple 
      sclerosis.
PG  - 658-66
LID - 10.1002/ana.21695 [doi]
AB  - OBJECTIVE: Multiple sclerosis (MS) is a chronic inflammatory disease affecting 
      the central nervous system. A human leukocyte antigen (HLA) class II association 
      is well established (DRB1*1501-DQB1*0602), but more recently HLA class 
      II-independent associations with HLA class I variants have also been reported. 
      The HLA class I (HLA-A, -B, -C) molecules serve as ligands for both T-cell 
      receptors and killer immunoglobulin-like receptors (KIRs). We investigated the 
      HLA class I alleles defined by their KIR binding motifs and the KIR genes to 
      evaluate whether these genes could influence MS susceptibility or severity, alone 
      or in combination. METHODS: We typed Norwegian MS patients (n = 631) and controls 
      (n = 555) for HLA-A, -B, -C and -DRB1 alleles as well as the presence or absence 
      of genes encoding inhibitory (KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL5, KIR3DL1, 
      KIR3DL2, KIR3DL3) and activating (KIR2DS1, KIR2DS2, KIR2DS3, KIR2DL4, KIR2DS4, 
      KIR2DS5, KIR3DS1) KIRs. RESULTS: The frequency of the HLA-Bw4 specificity, which 
      is the ligand for the inhibitory KIR3DL1, was significantly reduced in MS 
      patients as compared with controls (41.4% vs 55.1%, p(uncorrected (uc)) = 4.6 x 
      10(-6)). Also after stratifying for known HLA class II associations, the HLA-Bw4 
      association was seen (p(uc) = 0.002). No significant differences in gene carrier 
      frequencies of inhibitory and activating KIRs were observed. However, our data 
      indicate that MS patients who carry the activating KIR2DS2 and the inhibitory 
      KIR2DL2 genes have more severe disease than patients not carrying these genes. 
      INTERPRETATION: Carriage of the ligand of the inhibitory KIR3DL1 receptor, 
      HLA-Bw4, was found to protect against MS in an HLA-DRB1 independent manner.
FAU - Lorentzen, Aslaug R
AU  - Lorentzen AR
AD  - Department of Neurology, Faculty Division Ulleval, Oslo University Hospital, 
      University of Oslo, Oslo, Norway. a.r.lorentzen@medisin.uio.no
FAU - Karlsen, Tom H
AU  - Karlsen TH
FAU - Olsson, Marita
AU  - Olsson M
FAU - Smestad, Cathrine
AU  - Smestad C
FAU - Mero, Inger-Lise
AU  - Mero IL
FAU - Woldseth, Bente
AU  - Woldseth B
FAU - Sun, Ji-Yao
AU  - Sun JY
FAU - Senitzer, David
AU  - Senitzer D
FAU - Celius, Elisabeth G
AU  - Celius EG
FAU - Thorsby, Erik
AU  - Thorsby E
FAU - Spurkland, Anne
AU  - Spurkland A
FAU - Lie, Benedicte A
AU  - Lie BA
FAU - Harbo, Hanne F
AU  - Harbo HF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-Bw4 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Receptors, KIR)
SB  - IM
CIN - Ann Neurol. 2009 Jun;65(6):626-8. PMID: 19557875
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Female
MH  - Genetic Carrier Screening
MH  - HLA-B Antigens/genetics/metabolism/*physiology
MH  - HLA-DR Antigens/physiology
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*immunology/metabolism/*prevention & control
MH  - Protein Binding/immunology
MH  - Receptors, KIR/genetics/*metabolism/physiology
MH  - Young Adult
EDAT- 2009/07/25 09:00
MHDA- 2009/08/13 09:00
CRDT- 2009/07/25 09:00
PHST- 2009/07/25 09:00 [entrez]
PHST- 2009/07/25 09:00 [pubmed]
PHST- 2009/08/13 09:00 [medline]
AID - 10.1002/ana.21695 [doi]
PST - ppublish
SO  - Ann Neurol. 2009 Jun;65(6):658-66. doi: 10.1002/ana.21695.