PMID- 22185807
OWN - NLM
STAT- MEDLINE
DCOM- 20121112
LR  - 20211021
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 18
IP  - 7
DP  - 2012 Jul
TI  - Killer immunoglobulin-like receptor locus polymorphisms in multiple sclerosis.
PG  - 951-8
LID - 10.1177/1352458511431726 [doi]
AB  - OBJECTIVE: The objective of this study was to analyze whether inhibitory and 
      activating killer cell immunoglobulin-like receptors (KIRs) and human leukocyte 
      antigen (HLA) class I alleles defined by their KIR binding motifs are associated 
      with multiple sclerosis (MS) susceptibility or severity. METHOD: We performed a 
      population-based case-control study in 321 patients with clinically isolated 
      syndrome (CIS) and clinically definite MS (CDMS) and 156 healthy blood donors 
      (HD). Inhibitory and activating KIRs and HLA class I alleles were genotyped using 
      polymerase chain reaction (PCR) sequence-specific primers. Allelic frequencies 
      were correlated with prevalence, age of onset, disability and disease duration of 
      CIS and CDMS. RESULTS: The frequency of the inhibitory KIR2DL3 gene was 
      significantly reduced in patients with CIS and CDMS (p = 3.1 x 10(-5)). 
      KIR2DL3-dependent risk reduction remained significant after elimination of 
      patients carrying MS-associated DRB1*15, DRB1*03, DRB1*01 alleles. In addition, 
      individuals carrying two copies for KIR2DL2/KIR2DS2 but lacking KIR2DL3 were 
      overrepresented in the CIS/CDMS cohort. However, both genes did not affect 
      disease risk in presence of KIR2DL3. We did not detect any association between 
      the presence or absence of KIR genes with clinical disease parameters. 
      CONCLUSION: Absence of the inhibitory KIR2DL3 gene is associated with the 
      development of CIS/CDMS. These findings, if confirmed in larger cohorts, suggest 
      that KIR-mediated recognition of HLA class I molecules should be further explored 
      as potential disease mechanism in MS.
FAU - Jelcic, Ilijas
AU  - Jelcic I
AD  - Institute for Neuroimmunology and Clinical Multiple Sclerosis Research, 
      University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
FAU - Hsu, Katharine C
AU  - Hsu KC
FAU - Kakalacheva, Kristina
AU  - Kakalacheva K
FAU - Breiden, Petra
AU  - Breiden P
FAU - Dupont, Bo
AU  - Dupont B
FAU - Uhrberg, Markus
AU  - Uhrberg M
FAU - Martin, Roland
AU  - Martin R
FAU - Munz, Christian
AU  - Munz C
FAU - Lunemann, Jan D
AU  - Lunemann JD
LA  - eng
GR  - R01 CA108609/CA/NCI NIH HHS/United States
GR  - UO1 AI 069197/AI/NIAID NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01CA101741/CA/NCI NIH HHS/United States
GR  - R01CA108609/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111220
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (HLA-C Antigens)
RN  - 0 (KIR2DL3 protein, human)
RN  - 0 (Receptors, KIR)
RN  - 0 (Receptors, KIR2DL3)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Alleles
MH  - Case-Control Studies
MH  - Child
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease/*genetics
MH  - HLA-C Antigens/*genetics
MH  - Humans
MH  - Killer Cells, Natural/immunology
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*genetics/immunology
MH  - *Polymorphism, Genetic
MH  - Receptors, KIR/genetics
MH  - Receptors, KIR2DL3/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Young Adult
EDAT- 2011/12/22 06:00
MHDA- 2012/11/13 06:00
CRDT- 2011/12/22 06:00
PHST- 2011/12/22 06:00 [entrez]
PHST- 2011/12/22 06:00 [pubmed]
PHST- 2012/11/13 06:00 [medline]
AID - 1352458511431726 [pii]
AID - 10.1177/1352458511431726 [doi]
PST - ppublish
SO  - Mult Scler. 2012 Jul;18(7):951-8. doi: 10.1177/1352458511431726. Epub 2011 Dec 
      20.