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

Killer immunoglobulin-like receptor locus polymorphisms in multiple sclerosis

  • Jelčić, Ilijas Department of Neurology, University Hospital of Zürich, Switzerland
  • Hsu, Katharine C Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
  • Kakalacheva, Kristina Institute of Experimental Immunology, University of Zürich, Switzerland.
  • Breiden, Petra Institute for Neuroimmunology and Clinical Multiple Sclerosis Research, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
  • Dupont, Bo Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Uhrberg, Markus University Clinic of Düsseldorf, Institute for Transplantation Diagnostics and Cell Therapeutics, Düsseldorf, Germany
  • Martin, Roland Department of Neurology, University Hospital of Zürich, Switzerland
  • Münz, Christian Institute of Experimental Immunology, University of Zürich, Switzerland.
  • Lünemann, Jan D Department of Neurology, Charité-Universitätsmedizin Berlin, Germany
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  • 2011-12-20
Published in:
  • Multiple Sclerosis Journal. - SAGE Publications. - 2011, vol. 18, no. 7, p. 951-958
Neurology
Clinical Neurology
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/254208
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