@article{8af464ee0b2e42feb41e37fac032bee7,
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.",
keywords = "T cell, genes, multiple sclerosis, natural killer cell",
author = "Ilijas Jel{\v c}i{\'c} and Hsu, {Katharine C.} and Kristina Kakalacheva and Petra Breiden and Bo Dupont and Markus Uhrberg and Roland Martin and Christian M{\"u}nz and L{\"u}nemann, {Jan D.}",
note = "Funding Information: This study was supported by a grant from the Cancer Research Institute–Ludwig Institute for Cancer Research (to Dr Dupont), and by the National Institutes of Health (grant number NIAID UO1 AI 069197 to Dr Dupont and Dr Hsu). The study was in part further supported by the National Cancer Institute (grant numbers R01CA108609 and R01CA101741), the Foundation for the National Institutes of Health (Grand Challenges in Global Health) and the Swiss National Science Foundation (grant number 310030_126995) and the Dana Foundation{\textquoteright}s Neuroimmunology Program to Dr M{\"u}nz. Dr L{\"u}nemann is receiving grant support from the Swiss National Science Foundation, the Gemeinn{\"u}tzige Hertie-Stiftung, the Swiss Multiple Sclerosis Foundation, the Betty and David Koetser Foundation, the Ernst Schering Foundation, and the Baxter Research Grant Program. Dr L{\"u}nemann received further support from an Institutional Clinical and Translational Science and Collaborative Project Grant(to the Rockefeller University Hospital, Rockefeller University, New York, NY). Dr Jel{\v c}i{\'c} was supported by the Deutsche Forschungsgemeinschaft (grant number JE 530/1-1). The Institute for Neuroimmunology and Clinical Multiple Sclerosis Research is supported by the Gemeinn{\"u}tzige Hertie-Stiftung. The study sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. ",
year = "2012",
month = jul,
doi = "10.1177/1352458511431726",
language = "English",
volume = "18",
pages = "951--958",
journal = "Multiple Sclerosis Journal",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "7",
}