KIR Gene Frequencies in Women with Infertility Problems

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Eli Djulejic
Aleksandar Petlichkovski
Dejan Trajkov
Gligor Dimitrov
Sonja Alabakovska


Introduction: Natural killer (NK) cells are the predominant lymphocyte population in the decidua. Being the most abundant leucocytes, the activity of NK cells is important in different immuno-pathological conditions, such as recurrent spontaneous abortions, infertility and problems in implantation. The NK cells recognize HLA class I molecules on trophoblasts trough killer immunoglobulin-like receptors (KIRs) found on their surface. The KIRs are classified as either activating or inhibitory, regarding the effect they produce on NK cells upon interaction with corresponding ligand. Since KIR genes exhibit extensive polymorphism and individuals differ in both the number and kind (activating vs. inhibitory) of KIR genes, it is hypothesized that the KIR gene content might influence the pregnancy outcome.
Aim: The aim of this pilot study is to analyze the frequency of different KIR genes in women with infertility problems, and compare them to healthy women.
Material and Methods: Total of 122 healthy women (Control) and 25 women with reproductive problems (MISSC) participated in this study. After signing of written consent DNA was isolated from peripheral blood using phenol/chloroform method. The genotyping of 16 KIR genes was performed using commercially available kit from Dynal Biotech, (Pel-Freez Clinical Systems, Brown Deer, WI, USA), based on SSP method.
Results: We found that inhibitory KIR are present in similar observed frequency in both control and patients with MISSC, except KIR2DL5 which was found in lower frequency in patients with MISSC. There are no significant differences of all noninhibitory KIR between control and patients with MISSC. The number of inhibitory KIR genes in patients with MISSC was lover, except for seven inhibitory KIR genes which was almost doubled. The number of noninhibiotry (stimulatory) KIR genes was lower in patients with MISSC, except for those with three KIR genes which were almost four times more frequent. We found significantly bigger percentage of 0,34 – 0,60 activating/inhibitory KIR gene number ratio in the patients with MISSC.
Conclusion: In conclusion, there are differences in the KIR gene distribution, gene number, and activating/inhibitory KIR gene number ratio between control and Macedonian patients with MISSC. Further analysis of frequencies of corresponding KIR genotypes or in the ratio of activating/inhibiting genes content in two groups are needed.


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Djulejic, E., Petlichkovski, A., Trajkov, D., Dimitrov, G., & Alabakovska, S. (2015). KIR Gene Frequencies in Women with Infertility Problems. South East European Journal of Immunology (SEEJIM), 1(1), 1–5.


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