Lee S Nguyen1,2, Nathalie Rouas-Freiss3, Christian Funck-Brentano1, Monique Leban4, Edgardo D Carosella3, Philippe Touraine4,5, Shaida Varnous2, Anne Bachelot4, Joe-Elie Salem1,6. 1. Department of Pharmacology, Sorbonne Université, INSERM CIC Paris-Est, UNICO AP-HP.6 Cardio-Oncology Program, Pitié-Salpêtrière Hospital, Paris, France. 2. Department of Cardiothoracic Surgery, Sorbonne Université, Institute of Cardiology, Pitie-Salpetriere University Hospital, ICAN, Paris, France. 3. Department of Research in Hemato-Immunology (SRHI), CEA, Saint-Louis Institute, UMR U976, Paris, France. 4. Department of Endocrinology, Pitie-Salpetriere University Hospital, Sorbonne Universite, ICAN, Paris, France. 5. Center for Rare Endocrine Disorders and center for Rare Gynecological Disorders, Paris, France. 6. Department of Pharmacology and Medicine, Cardio-Oncology Program, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Abstract
BACKGROUND: HLA-G is an immune checkpoint molecule, naturally expressed during pregnancy, playing a critical role in the tolerance of the fetal semi-allograft from the maternal immune system. While HLA-G expression levels are associated with progesterone, the influence of other hormones is still unclear. Congenital adrenal hyperplasia (CAH) represents an adequate model to study the hormonal influence on biomarkers as it leads to impaired cortisol biosynthesis and increased progesterone and androgens production due to 21-hydroxylase enzyme deficiency. METHODS: In a cross-sectional study of CAH patients matched on sex and age with healthy control, the association between circulating levels of soluble HLA-G and hormones was assessed by use of non-parametric analyses tests. Multivariable linear regressions were performed on normalized data. RESULTS: Overall, 83 CAH patients and 69 healthy controls were included. Among CAH patients, all were under glucocorticoid and 52 (62.6%) were under mineralocorticoid supplementation. Compared to controls, CAH patients had increased HLA-G levels (15 vs 8 ng/mL, P = 0.02). In controls, HLA-G level was independently associated with progesterone and estradiol (β = 0.44 (0.35-1.27) and -0.44 (-0.94, -0.26) respectively, both P values = 0.001). In CAH patients, HLA-G level was independently associated with mineralocorticoid supplementation dosage (β = 0.25 (0.04-0.41), P = 0.001) and estradiol (β = -0.22 (-0.57, -0.02), P < 0.001). CONCLUSION: CAH patients had higher HLA-G levels than healthy controls. HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol. The association between mineralocorticoid, renin and HLA-G levels may suggest a role of the renin-angiotensin system in the expression of soluble HLA-G.
BACKGROUND: HLA-G is an immune checkpoint molecule, naturally expressed during pregnancy, playing a critical role in the tolerance of the fetal semi-allograft from the maternal immune system. While HLA-G expression levels are associated with progesterone, the influence of other hormones is still unclear. Congenital adrenal hyperplasia (CAH) represents an adequate model to study the hormonal influence on biomarkers as it leads to impaired cortisol biosynthesis and increased progesterone and androgens production due to 21-hydroxylase enzyme deficiency. METHODS: In a cross-sectional study of CAH patients matched on sex and age with healthy control, the association between circulating levels of soluble HLA-G and hormones was assessed by use of non-parametric analyses tests. Multivariable linear regressions were performed on normalized data. RESULTS: Overall, 83 CAH patients and 69 healthy controls were included. Among CAH patients, all were under glucocorticoid and 52 (62.6%) were under mineralocorticoid supplementation. Compared to controls, CAH patients had increased HLA-G levels (15 vs 8 ng/mL, P = 0.02). In controls, HLA-G level was independently associated with progesterone and estradiol (β = 0.44 (0.35-1.27) and -0.44 (-0.94, -0.26) respectively, both P values = 0.001). In CAH patients, HLA-G level was independently associated with mineralocorticoid supplementation dosage (β = 0.25 (0.04-0.41), P = 0.001) and estradiol (β = -0.22 (-0.57, -0.02), P < 0.001). CONCLUSION: CAH patients had higher HLA-G levels than healthy controls. HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol. The association between mineralocorticoid, renin and HLA-G levels may suggest a role of the renin-angiotensin system in the expression of soluble HLA-G.
Authors: Izabela Nowak; Karolina Wilczyńska; Paweł Radwan; Andrzej Wiśniewski; Rafał Krasiński; Michał Radwan; Jacek R Wilczyński; Andrzej Malinowski; Piotr Kuśnierczyk Journal: Front Immunol Date: 2020-01-14 Impact factor: 7.561
Authors: Lee S Nguyen; Edi Prifti; Farid Ichou; Monique Leban; Christian Funck-Brentano; Philippe Touraine; Joe-Elie Salem; Anne Bachelot Journal: Sci Rep Date: 2020-06-01 Impact factor: 4.379