Killer immunoglobulin-like receptor locus polymorphisms in multiple sclerosis Journal Article


Authors: Jelčić, I.; Hsu, K. C.; Kakalacheva, K.; Breiden, P.; Dupont, B.; Uhrberg, M.; Martin, R.; Münz, C.; Lünemann, J. D.
Article Title: Killer immunoglobulin-like receptor locus polymorphisms in multiple sclerosis
Abstract: 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 × 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. © The Author(s) 2012.
Keywords: adolescent; adult; child; controlled study; aged; middle aged; young adult; major clinical study; case-control studies; allele; genetic predisposition to disease; genes; prevalence; gene locus; genetic association; alleles; gene frequency; disease severity; reverse transcriptase polymerase chain reaction; hla antigen class 1; hla-c antigens; natural killer cell; killer cells, natural; killer cell immunoglobulin like receptor; receptors, kir; disease duration; risk reduction; disease predisposition; multiple sclerosis; age of onset; polymorphism, genetic; leukocyte antigen; genetic polymorphism; t cell; demyelinating disease; receptors, kir2dl3
Journal Title: Multiple Sclerosis
Volume: 18
Issue: 7
ISSN: 1352-4585
Publisher: Sage Publications  
Date Published: 2012-07-01
Start Page: 951
End Page: 958
Language: English
DOI: 10.1177/1352458511431726
PROVIDER: scopus
PUBMED: 22185807
DOI/URL:
Notes: --- - "Export Date: 1 August 2012" - "CODEN: MUSCF" - "Source: Scopus"
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MSK Authors
  1. Katharine C Hsu
    148 Hsu
  2. Bo Dupont
    196 Dupont