Abstract
Natural killer cells (NKs) are the most important cells in the fetomaternal immune tolerance induced through interaction of maternal killer-cell immunoglobulin-like receptors (KIR) and fetal human leucocyte antigens (HLA). Hence, we intend to perform a meta-analysis on the role of maternal KIR genes diversity in recurrent spontaneous abortion (RSA). The present paper is a meta-analysis of previous genetic association studies and our previous original study. The results showed that KIR3DL1 was a significantly protecting factor for RSA (p=0.044; OR=0.833 [0.698-0.995]; fixed effect model). KIR2DS2 (p=0.034; OR=1.195 [1.013-1.408]; fixed effect model) and KIR2DS3 (p=0.013; OR=1.246 [1.047-1.483]; fixed effect model) were significantly risk factors for RSA. For KIR2DS1 there was a high heterogeneity and publication bias. Briefly, the inhibitory gene KIR3DL1 was a protecting factor, and the activating genes KIR2DS2 and KIR2DS3 were risk factors for RSA. However, the effect sizes were not suitable. We suggest further studies on different causes of pregnancy loss, to find the role of KIR2DS1.
Highlights
RationaleRecurrent spontaneous abortion (RSA) and pregnancy loss have different pathogeneses, consisting of genetic and chromosomal abnormalities (Hume & Chasen, 2015), environmental toxicities and oxidative stress (Gupta et al., 2007), infectious agents (Ambühl et al, 2016), hormonal causes, etc
In our original study we showed that maternal KIR2DS1 in combination with paternal human leucocyte antigens (HLA)-C2 can be a risk factor (Akbari et al, 2018)
We found significant associations involving genes in the meta-analysis (Table 3), but these findings would not be reliable, because, 1) the odds ratios are not large enough to show a remarkable effect size; 2) the paper selection and homogenizing process of meta-analyses are different and customized among researchers; 3) there were a lot of missed data even in the cited studies; 4) pregnancy loss has a number of definitions such as abortion, stillbirth (Gold et al, 2010)
Summary
Recurrent spontaneous abortion (RSA) and pregnancy loss have different pathogeneses, consisting of genetic and chromosomal abnormalities (Hume & Chasen, 2015), environmental toxicities and oxidative stress (Gupta et al., 2007), infectious agents (Ambühl et al, 2016), hormonal causes, etc. Immunological causes and their involving molecules are still controversial and unknown topics. The immune system is a fascinating system, one that does not normally reject the semi-allograft fetus. The immune system has two roles in implantation and pregnancy; preventing the formation of abnormal embryos, and protecting the fetomaternal interaction by releasing angiogenic factors, cytokines and adhesive molecules. The fascinating point is how a system can have two mutually exclusive features; protection and rejection. The question is what the immune system does in this situation; rejection or protection (Akbari et al, 2018; Würfel, 2016)?!
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