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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-57398

Jelcic, I; Hsu, K C; Kakalacheva, K; Breiden, P; Dupont, B; Uhrberg, M; Martin, R; Münz, C; Lünemann, J D (2012). Killer immunoglobulin-like receptor locus polymorphisms in multiple sclerosis. Multiple Sclerosis, 18(7):951-958.

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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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:29 Jan 2012 14:29
Last Modified:08 Dec 2013 14:37
Publisher:Sage Publications
ISSN:1352-4585
Publisher DOI:10.1177/1352458511431726
PubMed ID:22185807
Citations:Web of Science®. Times Cited: 2
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Scopus®. Citation Count: 4

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