Protective effect of the KIR2DS1 gene in atopic dermatitis Wanda Niepiekło-Miniewska a , Edyta Majorczyk a , Łukasz Matusiak b , Ketevan Gendzekhadze c , Izabela Nowak a , Joanna Narbutt d , Aleksandra Lesiak d , Piotr Kuna e , Joanna Ponińska f , Aneta Pietkiewicz-Sworowska a , Bolesław Samoliński g , Rafał Płoski f , Jacek C. Szepietowski b , David Senitzer c , Piotr Kuśnierczyk a, ⁎ a Laboratory of Immunogenetics and Tissue Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Rudolfa Weigla 12, 53-114 Wrocław, Poland b Department of Dermatology, Venereology and Allergology, Medical University of Wroclaw, ul. T. Chałubińskiego 1, 50-368 Wrocław, Poland c City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA d 1st Department of Dermatology and Venereology, Medical University of Łódź, ul. Krzemieniecka 5, 94-014 Łódź, Poland e 2nd Chair of Internal Diseases, Medical University of Łódź, and N. Barlicki Medical University Hospital, ul. dr. S. Kopcińskiego 22, 90-153 Łódź, Poland f Department of Medical Genetics, Medical University of Warsaw, ul. Pawińskiego 3c, 01-106 Warsaw, Poland g Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, ul. S. Banacha, 02-097 Warsaw, Poland abstract article info Article history: Accepted 4 June 2013 Available online 4 July 2013 Keywords: Atopic dermatitis Killer cell immunoglobulin-like receptor HLA-C Genetics Atopic dermatitis (AD) is a common skin disease of complex etiology including affected humoral and cellular immune responses. The role of NK cells in development of this disease has been recently postulated, but is still poorly documented. The current study was undertaken to determine the impact of genes for the most polymorphic NK cell receptors, known as killer cell immunoglobulin-like receptors (KIRs), on the development of AD. We compared 240 patients suffering from AD with 570 healthy controls. Frequencies of the great majority of KIR genes did not differ between patients and controls, except for KIR2DS1, whose frequency was significantly (OR = 0.629, CI95% (0.45; 0.87), p corr = 0.0454) lower in patients than in controls. These results were confirmed in a second cohort of 201 patients. When both patient groups were combined and compared to the control group, the result for KIR2DS1 achieved even higher significance (OR = 0.658, CI95% (0.5; 0.86), p corr = 0.0158). To the best of our knowledge, this is the first report on KIR gene contribution to AD, and to allergy in general. © 2013 Published by Elsevier B.V. 1. Introduction Atopic dermatitis (AD) is a common (5–20% of population), chronic or relapsing skin disease of complex etiology, with interactions between susceptibility genes and environmental factors. Numerous immunologi- cal disturbances are observed in AD, including humoral and cellular, innate and adaptive responses (Boguniewicz and Leung, 2011; De Benedetto et al. 2009). Although the majority of immunological mecha- nisms in AD are relatively well known at present, the role of natural killer (NK) cells in the development of this disease is still poorly documented (Wollenberg and Klein, 2007). NK cells are involved in innate cytotoxicity as well as in regulation of immune (both innate and adaptive) responses (Boyton and Altmann, 2007; Parham, 2005). The most polymorphic NK cell receptors are known as killer cell immunoglobulin-like receptors (KIRs). Originally, these receptors were found on NK cells (Boyton and Altmann, 2007; Parham, 2005), but they could also be found on some T cells, especially on memory T cells (Rajagopalan and Long, 2005) and a rare subpopulation of CD4 + T cells deprived of CD28 expression (Goronzy and Weyand, 2003). Gene 527 (2013) 594–600 Abbreviations: AD, atopic dermatitis; CD, cluster of differentiation; CI95%, 95% confidence intervals; DNA, deoxyribonucleic acid; HLA, human leukocyte antigen; KIR, killer cell immunoglobulin-like receptor; LD, linkage disequilibrium; OR, odds ratio; p, probability; p corr , corrected p; PCR-SSP, polymerase chain reaction using sequence-specific primers; SCORAD, scoring atopic dermatitis, index of disease severity; UV, ultraviolet. ⁎ Corresponding author at: Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Rudolfa Weigla 12, PL-53-114 Wroclaw, Poland. Tel.: +48 71 3709976; fax: +48 71 3371382. E-mail address: pkusnier@iitd.pan.wroc.pl (P. Kuśnierczyk). Table 1 Characteristics of atopic dermatitis (AD) patients. Parameter Subgroup First cohort (N = 240) Second cohort (N = 201) N % N % Gender Males 98 40.8 91 45.2 Females 142 59.2 110 54.8 Age groups 2–12 years 104 43.3 70 34.7 13–62 years 136 56.7 131 65.3 Co-morbidities Asthma 72 30.0 15 7.5 Rhinitis 94 39.2 55 27.1 Conjunctivitis 50 20.8 – – –, data not available. 0378-1119/$ – see front matter © 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.gene.2013.06.015 Contents lists available at SciVerse ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene