Decreased HLA-C1 alleles in couples of KIR2DL2 positive women with recurrent pregnancy loss

Yang, Xiuhua; Yang, Ellen; Wang, Wen‐Juan; He, Qin; Jubiz, Giovanni; Katukurundage, Dimantha; Dambaeva, Svetlana; Beaman, Kenneth D.; Kwak‐Kim, Joanne

doi:10.1016/j.jri.2020.103186

Cited by 17 publications

(10 citation statements)

References 51 publications

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“…The morbidity of RPL is 5% among couples of childbearing age [64]. Many reasons may lead to RPL, such as genetic issues 3 BioMed Research International [65], chromosomal abnormalities, anatomical deformities, endocrine problems, and immune diseases [66].…”

Section: Hct and Rplmentioning

confidence: 99%

A Novel Review of Homocysteine and Pregnancy Complications

Dai

Fei

et al. 2021

BioMed Research International

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Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B6 and B12 deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

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Section: Hct and Rplmentioning

confidence: 99%

A Novel Review of Homocysteine and Pregnancy Complications

Dai

Fei

et al. 2021

BioMed Research International

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“…Amidst these, the etiology of certain patients is unknown and may be related to autoimmune abnormalities. The correlation between KIR/HLA-C combination and RPL is listed in Table I, a few are inconsistent (14)(15)(16)(17)19,25,26,(59)(60)(61)(62)(63)(64)(65). Reportedly, RPL females had an elevated rate of maternal KIR AA haplotype and fetal HLA-C2 binding (14,15,60,66).…”

Section: Kir/hla-c Combination and Gosmentioning

confidence: 99%

“…Initially, the authors established that KIRs in partners could not directly result in a miscarriage; however, since the fetal KIR genotype is unclear, distributed fetal cells with potentially unfavorable KIRs can accelerate the ending course (65). It was recently reported that KIR2DL2-positive RPL females exhibited decreased molecules of HLA-C1 compared with KIR2DL2-negative RPL females (P<0.05) (26). Reduced ligands for inhibiting KIRs may cause inadequate inhibition of maternal uNK cells to the trophoblast, thus giving rise to RPL.…”

Section: Kir/hla-c Combination and Gosmentioning

confidence: 99%

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Killer‑cell immunoglobulin‑like receptor/human leukocyte antigen‑C combination and ‘great obstetrical syndromes’ (Review)

Yang

Meng

2021

Exp Ther Med

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Recurrent pregnancy loss (RPL), pre-eclampsia (PE), fetal growth restriction (FGR), and preterm delivery are examples of 'great obstetrical syndromes' (GOS). Placental dysfunction is the most common pathogenesis of GOS. In human pregnancies, the effects of uterine natural killer cells involve angiogenesis, promoting the remodeling of uterine spiral artery, and improving the invasion of trophoblast cells. The uNK cells supply killer immunoglobulin-like receptors (KIRs), which come into contact with human leukocyte antigen-C (HLA-C) ligands expressed by extravillous trophoblast cells (EVTs). Numerous studies have investigated the association between GOS and KIR/HLA-C combination. However, the outcomes have not been conclusive. The present review aimed to reveal the association between GOS and KIR/HLA-C combination to screen out high-risk pregnancies, strengthen the treatment of pregnancy complications, and reduce the frequency of adverse maternal and fetal outcomes. It has been reported that a female with a KIR AA genotype and a neonate with a paternal HLA-C2 molecule is more prone to develop GOS and have a small fetus since less cytokines were secreted by uNK cells. Conversely, the combination of KIR BB haplotype (including the activating KIR2DS1) and HLA-C2 can induce the production of cytokines and increase trophoblast invasion, leading to the birth of a large fetus. KIR/HLA-C combinations may be applicable in selecting third-party gametes or surrogates. Detection of maternal KIR genes and HLA-C molecules from the couple could serve as useful markers for predicting and diagnosing GOS.

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“…It can be divided into two types: primary RPL (previously no child) and secondary RPL (consecutive abortions after a live child). The etiology of RPL includes genetic, environmental, anatomical, endocrine, immune, and microbial infection factors [4][5][6]. However, nearly half of the RPL patients are called unexplained RPL due to unknown etiology.…”

Section: Introductionmentioning

confidence: 99%

Is there a Role of Intravenous Immunoglobulin in Immunologic Recurrent Pregnancy Loss?

Yang

Meng

2020

Journal of Immunology Research

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Recurrent pregnancy loss (RPL) commonly refers to three or more miscarriages that occur before 20 weeks of pregnancy. The immunological cause of RPL could be either an auto- or alloimmune-related event or both. Because of the discovery of immunological abnormalities in RPL patients in clinical practice, several immunomodulatory therapies were introduced to maintain the immune balance at the maternal-fetal interface. Intravenous immunoglobulin (IVIg) is one of the immunomodulators. In recent years, several studies have analyzed the therapeutic effect of IVIg on RPL patients with antiphospholipid syndrome (APS) or unexplained RPL. However, their results are controversial. IVIg can be used in RPL patients with APS who have previously failed in other treatments. It is recommended that IVIg infusion could be considered used before conception in RPL patients who have cellular immune abnormalities such as increased natural killer (NK) cell counts, NK cell cytotoxicity, or increased T helper (Th)1/Th2 ratio, depending on the cut-off values of each hospital. The aim of this review was to summarize the mechanisms, efficacy, pharmacokinetics, and side effects associated with passive immunization using IVIg in immunologic RPL, according to the literature published in recent years. We hope that more obstetricians will be able to understand the timing and indication of IVIg properly in immunologic RPL patients and effectively enhance pregnancy outcomes for mothers and neonates.

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Decreased HLA-C1 alleles in couples of KIR2DL2 positive women with recurrent pregnancy loss

Cited by 17 publications

References 51 publications

A Novel Review of Homocysteine and Pregnancy Complications

A Novel Review of Homocysteine and Pregnancy Complications

Killer‑cell immunoglobulin‑like receptor/human leukocyte antigen‑C combination and ‘great obstetrical syndromes’ (Review)

Is there a Role of Intravenous Immunoglobulin in Immunologic Recurrent Pregnancy Loss?

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