404 Basic Science http://www.mjms.ukim.edu.mk Macedonian Journal of Medical Sciences. 2012 Dec 15; 5(4):404-410. http://dx.doi.org/10.3889/MJMS.1857-5773.2012.0270 Basic Science Association of Killer Cell Immunoglobulin-Like Receptor Genes with the Graft versus Host Disease after Related Haematopoietic Stem Cell Transplantation in Patients with Haematological Malignancies from Republic of Macedonia Aleksandar Petlichkovski 1 , Zlate Stojanoski 2 , Eli Djulejic 3 , Borce Georgievski 2 , Mirko Spiroski 1 1 Institute of Immunobiology and Human Genetics, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia; 2 University Clinic of Haematological Diseases, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia; 3 Quintiles, Belgrade, Republic of Serbia Citation: Petlichkovski A, Stojanoski Z, Djulejic E, Georgievski B, Spiroski M. Association of Killer Cell Immunoglobulin-Like Receptor Genes with the Graft versus Host Disease after Related Haematopoietic Stem Cell Transplantation in Patients with Haematological Malignancies from Republic of Macedonia. Maced J Med Sci. 2012 Dec 15; 5(4):404-410. http://dx.doi.org/10.3889/ MJMS.1857-5773.2012.0270. Key words: Killer immunoglobulin-like receptor (KIR) gene polymorphism; HLA and KIR genotyping; KIR2DS4; Macedonian patients with HSCT; GVHD. Correspondence: Mirko Spiroski, MD, PhD. Institute of Immunobiology and Human Genetics, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, 1109 Skopje, PO Box 60, Republic of Macedonia. Tel.: +389-2-3110556. Fax: +389-2-3110558. E-mail: mspiroski@yahoo.com Received: 21-Sep-2012; Revised: 15-Nov-2012; Accepted: 07-Dec-2012; Online first: 09-Dec-2012 Copyright: © 2012 Petlichkovski A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Competing Interests: The author have declared that no competing interests exist. Abstract Aim: The aim of this study was to examine the gene frequencies of 16 KIR genes and pseudogenes and KIR genotypes in Macedonian patients with transplanted bone marrow and their sibling donors in treatment of haematological malignancy, and to analyse eventual association of the gene content with the occurrence of a graft versus host disease (GVHD). Material and Methods: The study was performed on 24 patients and their HLA-matched sibling donors. Results: Comparison of KIR gene frequencies between the total 24 donors and healthy Macedonians reveals statistically significant difference for KIR2DS1 (F= 0.481 in the controls group, and 0.76 in the patients group, p=0.004). This significance is even higher when the frequency of KIR2DS1 in controls is compared with the frequency in donors from pairs with GVHD (F= 0.923, P= 0.002). Another significant difference was observed for the frequency of the full-length allele of KIR2DS4*001-002, present in 25.2% of the control individuals, but in as much as 81.8% of the recipients of haematopoietic stem cell (P=0.0005). We did not see any statistically significant difference in distribution of the C1/C1, C1/C2 and C2/C2 groups among GVHD pairs. Conclusion: Our results address the difference between the haematopoietic stem cell transplantation settings with sibling and unrelated donors and suggest that the KIR2DS4*001/002 might be a predisposing factor for severe GVHD in sibling HSCT. Introduction Over the last three decades, the transplantation of haematopoietic stem cells coming from bone marrow or peripheral blood from related and unrelated donors has become widely recognized as the only curative treatment for different haematological malignancies and other diseases. Despite of the major advances in histocompatibility testing techniques, more aggressive matching programs, and the developement of more efficient immunosuppressive drugs, this therapeutic procedure is still burdened with a relatively high mortality rate, which ranges between 10 and 30% [1-4]. As an increasing number of transplants are being performed in OPENACCESS