References:

1. Role of HLA in Miscarriage ZohrehDorostkar1*, Abbas Nikravesh2 ,MajidSadeghizadeh 1. Department of Genetics, Faculty of Biological Sciences, Zabol University, Tehran, Iran. 2. Department of Genetics, Faculty of Biological Sciences, Birjand University, Tehran, Iran. 3. Department of Genetics, Faculty of Biological Sciences, TarbiatModares University, Tehran, Iran. Corresponding author’s E-mail: venousezd@yahoo.com Abstract: During pregnancy, the maternal immune system is in close contact with cells and tissue from the semiallogenicfetus .The human leucocyte antigen (HLA) class Ib molecules, HLA-E, -F and -G, are expressed at the materno-fetal interface. Because of the apparent immunoregulatoryfunctions of these proteins, they may be involved in successful acceptance of the semi-allogenicfetus during pregnancy.in this presentation we have reviewed studies regarding role of hla class Ibin pregnancy success and gathered their results in order to gain a better understanding of the relationship of these molecule and pregnancy success. Results and Discussion: HLA-G protein has been detected only in fetal cells at the maternal-fetal interface. HLA-G has been detected in human prostatic tissue in one study, and even though HLA-G1 mRNA was the most prominent transcript found, This study also found HLA-G expression in normal testis and epididymal tissues indicates that sHLA-G may have immunoregulatory roles during fertilization and implantation .Soluble HLA-G: a possible biomarker in human reproduction.They showed levels of sHLA-G in 20 IVF treated women with subsequent miscarriages were much lower than in 45 women with intact pregnancies HLA-E protein could be detected in all cell populations expressing either membrane-bound or soluble HLA-G including EVT, VT and ST cells. HLA-E were able to inhibit cytolysis carried out by NK cells through the CD94/NKG2A receptor HLA-F might be involved in regulating the immune response during pregnancy by serving as a marker of maternal activated lymphocytes, interacting with the regulatory T cells making them secrete inhibitory cytokine and induce suppressive signalling, which will result in the generation of tolerance. Although HLA-C belongs to the classical HLA class Ia molecules it has similarities with the non-classical HLA molecules in relation to pregnancy success. HLA-C is expressed on the surface of EVT cells both as b2m-associated molecules and as free heavy chains. Regarding receptor interactions, HLA-C has been shown to interact with Killer inhibitory receptor 2Dl receptors, which are expressed on the surface of uNK cells. Results: Non-classical antigens such as Human leukocyte Antigen class Ib may interact with receptors of NK cells ,Macrophage, CD8+ Tcell,CD4+ T cell and monocyte such as Killer Inhibitory Receptor,LeukocyteIg Like Receptor which results into limit activity of these immune cells and downregulation of immune response and helps in the maintenance of pregnancy and any changes in pattern of expression of these HLA molecule because of polymorphisms or other reason may cause misscarriage. • Introduction: • A miscarriage is the loss (death) of a baby before the 20th week of pregnancy.According to the March of Dimes, as many as 50% of all pregnancies end in miscarriage. More than 80% of miscarriages occur with in the first three months of pregnancy. • Causes Miscarriage :Infection(Exposure to environmental and workplace hazards such as high levels of radiation or toxic agents), Hormonal problems(Lifestyle factors such as smoking, drinking alcohol, or using illegal drugs). Genetic causes(Autosomal trisomy, Monosomy X, Tetraploidy, Structural rearrangement of the chromosomes). Disorders of the immune system(As much as 40 percent of unexplained infertility may be the result of immune problems Scientists have long suspected that variations in the expression of Human Leukocyte Antigen (HLA) may play a role in pregnancy outcome. Materials and Methods: We have conducted a thorough literature search using search engines in the medical databases and collected the data and research results regarding these molecules and pregnancy.wefocused on polymorphisms of the three genes, expression patterns of the proteins, and interactions with immune cells and the have been evaluated to elucidate whether HLA-E, -F and -G are involved in the pathogenesis recurrent miscarriages. Conclusion: the HLA class Ib molecules seem to induce suppression of the maternal immune system. evidences show changes in expression pattern and function of these molecules are associated with miscarriage . to clarify the functions of HLA-E, -F and -G future studies need to link investigations of the polymorphisms in these genes to measurements of protein levels, and examine the role of these proteins in the complex interplay of immune cells and cytokines at the materno-fetal interface. • References: • Zhang M, Weng X, Liang Z, Lu S, Li J, Chen X, Li Q, Sun W, Song Y, Shen G et al. Dimerization of soluble HLA-G by IgG-Fc fragment augments ILT2-mediated inhibition of T cell alloresponse. Transplantation 2009,87:8–15. • 2) Zhu Y, Huo Z, Lai J, Li S, Jiao H, Dang J, Jin C. Case–control study of a HLA-G 14-bp .insertion-deletion polymorphism in women with recurrent miscarriages. Scand J Immunol.2010,71:52–54.