Influence of hormones on the immunotolerogenic molecule HLA-G: a cross-sectional study in patients with congenital adrenal hyperplasia

Nguyen, Lee S.; Rouas‐Freiss, Nathalie; Funck‐Brentano, Christian; Leban, Monique; Carosella, Edgardo D.; Touraine, Philippe; Varnous, Shaïda; Bachelot, Anne; Salem, Joe‐Elie

doi:10.1530/eje-19-0379

Cited by 9 publications

(8 citation statements)

References 27 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, sex hormones were shown to influence soluble HLA-G levels in congenital adrenal hyperplasia (CAH) patients. Here, CAH patients had higher soluble HLA-G levels than healthy controls and HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol (45). Androgens including testosterone have been shown to have anti-inflammatory properties and a negative correlation between testosterone and TNFα levels in umbilical cord serum was found (46).…”

Section: Discussionmentioning

confidence: 75%

Three types of HLA-G+ extravillous trophoblasts that have distinct immune regulatory properties

Papúchová

Kshirsagar

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

During pregnancy, invading HLA-G+ extravillous trophoblasts (EVT) play a key role in placental development, uterine spiral artery remodeling, and prevention of detrimental maternal immune responses to placental and fetal antigens. Failures of these processes are suggested to play a role in the development of pregnancy complications, but very little is known about the underlying mechanisms. Here we present validated methods to purify and culture primary HLA-G+ EVT from the placental disk and chorionic membrane from healthy term pregnancy. Characterization of HLA-G+ EVT from term pregnancy compared to first trimester revealed their unique phenotypes, gene expression profiles, and differing capacities to increase regulatory T cells (Treg) during coculture assays, features that cannot be captured by using surrogate cell lines or animal models. Furthermore, clinical variables including gestational age and fetal sex significantly influenced EVT biology and function. These methods and approaches form a solid basis for further investigation of the role of HLA-G+ EVT in the development of detrimental placental inflammatory responses associated with pregnancy complications, including spontaneous preterm delivery and preeclampsia.

show abstract

Section: Discussionmentioning

confidence: 75%

Three types of HLA-G+ extravillous trophoblasts that have distinct immune regulatory properties

Papúchová

Kshirsagar

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Crohn’s disease, Behçet’s disease, multiple sclerosis, or organ transplant are associated with sHLA-G expression ( 116 – 119 ); (5) IVF factors such as maternal age, cycle type (frozen cycles or fresh cycles), or exogenous hormone supplementation may change sHLA-G levels ( 8 ). It is reported that HLA-G expression was positively associated with progesterone supplementation but negatively with estradiol ( 120 ) and maternal age; (6) The detection of sHLA-G level in most cases is limited to sHLA-G1/HLA-G5 isotype measured by ELISA due to restriction in antibodies. Whereas the expression pattern of the other isoforms is rarely analyzed.…”

Section: Discussionmentioning

confidence: 99%

Association of parental HLA-G polymorphisms with soluble HLA-G expressions and their roles on recurrent implantation failure: A systematic review and meta-analysis

Zeng

2022

Front. Immunol.

View full text Add to dashboard Cite

IntroductionHLA-G plays a central role in immune tolerance at the maternal-fetal interface. The HLA-G gene is characterized by low allelic polymorphism and restricted tissue expression compared with classical HLA genes. HLA-G polymorphism is associated with HLA-G expression and linked to pregnancy complications. However, the association of parental HLA-G polymorphisms with soluble HLA-G (sHLA-G) expression and their roles in recurrent implantation failure (RIF) is unclear. The study aims to systematically review the association of HLA-G polymorphisms with RIF, the association of sHLA-G expression with RIF, and the association of HLA-G polymorphisms with sHLA-G expressions in patients attending in-vitro fertilization (IVF) treatment.MethodsStudies that evaluated the association of HLA-G polymorphisms with RIF, the association between sHLA-G expression with RIF, and the association between HLA-G polymorphisms with sHLA-G expressions in patients attending IVF treatment were included. Meta-analysis was performed by random-effect models. Sensitivity analysis was performed by excluding one study each time. Subgroup analysis was performed based on ethnicity.ResultsHLA-G 14bp ins variant is associated with a lower expression of sHLA-G in seminal or blood plasma of couples attending IVF treatment. The maternal HLA-G*010101 and paternal HLA-G*010102 alleles are associated with RIF risk compared to other alleles. However, single maternal HLA-G 14bp ins/del polymorphism, HLA-G -725 C>G/T polymorphism, or circulating sHLA-G concentration was not significantly associated with RIF in the general population. HLA-G 14bp ins/ins homozygous genotype or ins variant was associated with a higher risk of RIF in the Caucasian population.DiscussionSpecific HLA-G alleles or HLA-G polymorphisms are associated with sHLA-G expression in couples attending IVF treatment. Several HLA-G polymorphisms may be related to RIF, considering different ethnic backgrounds. A combined genetic effect should be considered in future studies to confirm the association of HLA-G polymorphisms and sHLA-G expressions in relation to RIF.

show abstract

“…Hyperplasia (CARDIOHCS) study (clinicaltrials.gov identifier NCT01807364), a multicenter prospective observational case-control study comparing early cardiovascular damage in adult men and women with CAH due to 21α-hydroxylase deficiency and healthy control subjects 13,19,20 . All participants provided written informed consent to participate, and the study was approved by each hospital ethics committee including Pitie-Salpetriere University Hospital.…”

Section: Study Design This Study Is Ancillary To the Cardiovascular mentioning

confidence: 99%

“…women and 26 men) with CAH and 84 control subjects matched for sex, age, and smoking status were prospectively included in the CARDIOHCS study between May 2011 and August 2015 13,19,20 . The adults with CAH included in the study, were diagnosed during childhood and confirmed by genetic testing of 21α-hydroxylase deficiency.…”

Section: Study Populationmentioning

confidence: 99%

Effect of congenital adrenal hyperplasia treated by glucocorticoids on plasma metabolome: a machine-learning-based analysis

Nguyen

Prifti

Ichou

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Background. Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to impaired cortisol biosynthesis. Treatment includes glucocorticoid supplementation. We studied the specific metabolomics signatures in CAH patients using two different algorithms. Methods. In a case-control study of CAH patients matched on sex and age with healthy control subjects, two metabolomic analyses were performed: one using MetaboDiff, a validated differential metabolomic analysis tool and the other, using Predomics, a novel machine-learning algorithm. Results. 168 participants were included (84 CAH patients). There was no correlation between plasma cortisol levels during glucocorticoid supplementation and metabolites in CAH patients. Indoleamine 2,3-dioxygenase enzyme activity was correlated with ACTH (rho coefficient = −0.25, p-value = 0.02), in CAH patients but not in controls subjects. Overall, 33 metabolites were significantly altered in CAH patients. Main changes came from: purine and pyrimidine metabolites, branched aminoacids, tricarboxylic acid cycle metabolites and associated pathways (urea, glucose, pentose phosphates). MetaboDiff identified 2 modules that were significantly different between both groups: aminosugar metabolism and purine metabolism. Predomics found several interpretable models which accurately discriminated the two groups (accuracy of 0.86 and AUROC of 0.9). Conclusion. CAH patients and healthy control subjects exhibit significant differences in plasma metabolomes, which may be explained by glucocorticoid supplementation. Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases due to enzyme deficiencies leading to impaired cortisol biosynthesis and deficiency of the 21-hydroxylase enzyme is its most common form. Main treatment relies on steroid replacement therapy including glucocorticoids (GC) (i.e. hydrocortisone) alone or in association with mineralocorticoids (i.e. fludrocortisone) 1. Although effective, long-term GC replacement therapy is associated with multiple adverse effects. They include, but are not limited to the appearance of cardiovascular metabolic risk factors (hypertension, insulin-resistance, obesity and dyslipidemia), immunosuppression with infections, psychological disturbances and osteoporosis. Moreover, oral GC intake does not supplement adequately cortisol's physiological circadian rhythm, and the dosage needed to suppress androgens is usually higher than that needed for substitution only 2. These elements all contribute to increased health costs and decrease of quality of life and life expectancy 2-6 .

show abstract

Influence of hormones on the immunotolerogenic molecule HLA-G: a cross-sectional study in patients with congenital adrenal hyperplasia

Cited by 9 publications

References 27 publications

Three types of HLA-G+ extravillous trophoblasts that have distinct immune regulatory properties

Three types of HLA-G+ extravillous trophoblasts that have distinct immune regulatory properties

Association of parental HLA-G polymorphisms with soluble HLA-G expressions and their roles on recurrent implantation failure: A systematic review and meta-analysis

Effect of congenital adrenal hyperplasia treated by glucocorticoids on plasma metabolome: a machine-learning-based analysis

Contact Info

Product

Resources

About