The Immunosignature of Mother/Fetus Couples in Gestational Diabetes Mellitus: Role of HLA-G 14 bp ins/del and PAPP-A A/C Polymorphisms in the Uterine Inflammatory Milieu

Martinetti, Miryam; Beneventi, Fausta; Capittini, Cristina; Locatelli, Elena; Simonetta, Margherita; Cavagnoli, Chiara; Maggio, Irene De; Silvestri, Annalisa De; Pasi, Annamaria; Spinillo, Arsenio

doi:10.1155/2017/4254750

Cited by 8 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was noticed that for diagnosis of GDM, HLA-G at cutoff point > 0.7 had 94% sensitivity and 91% specificity with overall accuracy of 93%. In concordance with our findings, Martinetti and colleagues [20] evaluated 151 non-GDM women and 26 pregnant women with GDM. HLA-G plasma levels were measured by ELISA method at first and second trimesters of pregnancy, at delivery, and in cord blood.…”

Section: Discussionsupporting

confidence: 91%

Soluble human leukocyte antigen-G evaluation in pregnant women with gestational diabetes mellitus

et al. 2020

View full text Add to dashboard Cite

Background Gestational diabetes mellitus is any degree of glucose intolerance with onset or first recognition occurring late in second trimester and third trimester of pregnancy. It constitutes a greater impact on diabetes epidemic as it carries a major risk for developing type 2 diabetes mellitus to the mother and her fetus later in life. human leukocyte antigen (HLA)-G is a class Ib gene presents in the human major histocompatibility complex (MHC). HLA-G has an important role for mother and fetus tolerance during pregnancy, also in the pancreatic islet cells protection. This is a case-control study, measuring serum HLA-G levels by ELISA in 60 pregnant women with gestational diabetes compared with 36 normal pregnant women. Results HLA-G levels were significantly high in pregnant women with gestational diabetes mellitus (GDM) in contrast to women with normal pregnancy (P = 0.001). Conclusion Women with GDM had significantly higher levels of soluble HLA-G than women without GDM, suggesting that HLA-G molecule is among the factors for regulation and control of the immune response and the induction of tolerance. Soluble HLA-G could be considered an important follow-up investigation for all pregnant primary health care for early detection of gestational diabetes.

show abstract

Section: Discussionsupporting

confidence: 91%

Soluble human leukocyte antigen-G evaluation in pregnant women with gestational diabetes mellitus

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The authors concluded that their results showed an association between the degree of glucose intolerance and increased levels of serum HLA‐G that is in accordance with the results of Solini et al who studied the association between HLA‐G and obesity 20,42 . Beneventi was among the co‐workers of a later study by Martinetti et al who found that HLA‐G 14 bp del/del genotype was slightly more frequent in GDM mothers (OR = 1.7) and babies born to GDM mothers (OR = 2.1) than in controls 43 …”

Section: Discussionsupporting

confidence: 86%

Decreased serum human leukocyte antigen‐G levels are associated with gestational diabetes mellitus

Öztekin

Çabuş

Enli

2021

J of Obstet and Gynaecol

View full text Add to dashboard Cite

Aim This study was designed to determine serum human leukocyte antigen‐G (HLA‐G) levels and establish whether serum HLA‐G level is related with gestational diabetes mellitus (GDM). Methods Twenty‐five GDM patients aged between 24 and 34 years and 24 healthy pregnant women aged between 22 and 33 years were included in this study. Health status of subjects was determined by medical history, physical, and obstetric examinations. Absence of family history for Type 2 diabetes mellitus, absence of diagnosis or clinical evidence of any major disease, and absence of medication use altering glucose metabolism constituted the inclusion criteria. GDM cases who are at their 24–28 weeks of pregnancy and who have not been using any oral hypoglycemic agents were included in GDM group. Control group consisted of healthy pregnant women at their 24–28 weeks of pregnancy. Results Women with GDM had significantly lower levels of serum HLA‐G than controls. HLA‐G levels were negatively correlated with all parameters of glucose metabolism including insulin (r = − 0.14; p = 0.338), fasting blood glucose (r = − 0.220; p = 0.129), 1‐h oral glucose tolerance test (OGTT) blood glucose (r = − 0.18; p = 0.271), 2‐h OGTT blood glucose (r = − 0.314; p = 0.172), homeostasis model assessment (r = − 0.226; p = 0.119), HbA1C (r = −0.342; p = 0.108), and WBC (r = −0.149; p = 0.307). There was a negative correlation between HLA‐G and BMI (r = −0.341; p = 0.016). Conclusion Decreased circulating HLA‐G level is found to be associated with insulin resistance and GDM, in this study.

show abstract

“…Besides recurrent pregnancy loss the rs7020782 SNP in PAPPA also associates with the risk of gestational diabetes mellitus, risk of developing carotid plaques, and risk for ischemic cerebrovascular disease 30–32 . An altered IGF bioactivity may be present in these cases, because of the reduced proteolysis of IGFBPs by PAPP-A, however, none of these studies included examinations of PAPP-A activity.…”

Section: Discussionmentioning

confidence: 99%

A common variant of the pregnancy-associated plasma protein-A (PAPPA) gene encodes a protein with reduced proteolytic activity towards IGF-binding proteins

Bøtkjær

Noer

Oxvig

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Pregnancy-associated plasma protein-A (PAPP-A) is a key regulator of insulin-like growth factor (IGF) bioactivity, by releasing the IGFs from their corresponding IGF-binding proteins (IGFBPs). The minor allele of the single nucleotide polymorphism (SNP), rs7020782 (serine < tyrosine), in PAPPA has previously been associated with recurrent pregnancy loss as well as with significant reduced levels of PAPP-A protein in human ovarian follicles. The aim of the present study was to reveal a possible functional effect of the rs7020782 SNP in PAPPA by comparing recombinant PAPP-A proteins from transfected human embryonic kidney 293 T cells. The proteolytic cleavage of IGFBP-4 was shown to be affected by the rs7020782 SNP in PAPPA, showing a significantly reduced cleavage rate for the serine variant compared to the tyrosine variant (p-value < 0.001). The serine variant also showed a trend towards reduced cleavage rates, that was not significant, towards IGFBP-2 and IGFBP-5 compared to the tyrosine variant. No differences were found when analysing cell surface binding, complex formation between PAPP-A and STC2 or proMBP, nor when analysing STC1 inhibition of PAPP-A-mediated IGFBP-4 cleavage. Regulation of IGF bioactivity in reproductive tissues is important and the rs7020782 SNP in PAPPA may disturb this regulation by altering the specific activity of PAPP-A.

show abstract

The Immunosignature of Mother/Fetus Couples in Gestational Diabetes Mellitus: Role of HLA-G 14 bp ins/del and PAPP-A A/C Polymorphisms in the Uterine Inflammatory Milieu

Cited by 8 publications

References 26 publications

Soluble human leukocyte antigen-G evaluation in pregnant women with gestational diabetes mellitus

Soluble human leukocyte antigen-G evaluation in pregnant women with gestational diabetes mellitus

Decreased serum human leukocyte antigen‐G levels are associated with gestational diabetes mellitus

A common variant of the pregnancy-associated plasma protein-A (PAPPA) gene encodes a protein with reduced proteolytic activity towards IGF-binding proteins

Contact Info

Product

Resources

About