Department of Pharmacology, Sorbonne Université, INSERM CIC Paris-Est, UNICO AP-HP.6 Cardio-Oncology Program, Pitié-Salpêtrière Hospital, Paris, France.
Department of Cardiothoracic Surgery, Sorbonne Université, Institute of Cardiology, Pitie-Salpetriere University Hospital, ICAN, Paris, France.
Eur J Endocrinol. 2019 Nov;181(5):481-488. doi: 10.1530/EJE-19-0379.
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.
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.
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).
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.
HLA-G 是一种免疫检查点分子，在怀孕期间自然表达，在母体免疫系统对胎儿半同种异体的耐受中发挥关键作用。虽然 HLA-G 的表达水平与孕激素有关，但其他激素的影响仍不清楚。先天性肾上腺增生症（CAH）代表了一个研究激素对生物标志物影响的理想模型，因为它会导致皮质醇生物合成受损，由于 21-羟化酶缺乏，孕激素和雄激素的产生增加。
在一项 CAH 患者与健康对照者按性别和年龄匹配的横断面研究中，使用非参数分析检验评估循环可溶性 HLA-G 与激素之间的关系。对归一化数据进行多元线性回归分析。
共纳入 83 例 CAH 患者和 69 例健康对照者。CAH 患者均接受糖皮质激素治疗，52 例（62.6%）接受盐皮质激素补充治疗。与对照组相比，CAH 患者的 HLA-G 水平升高（15 与 8ng/ml，P=0.02）。在对照组中，HLA-G 水平与孕激素和雌二醇独立相关（β=0.44（0.35-1.27）和-0.44（-0.94，-0.26），P 值均=0.001）。在 CAH 患者中，HLA-G 水平与盐皮质激素补充剂量独立相关（β=0.25（0.04-0.41），P=0.001）和雌二醇（β=-0.22（-0.57，-0.02），P<0.001）。
CAH 患者的 HLA-G 水平高于健康对照组。HLA-G 水平与孕激素和皮质激素补充呈正相关，与雌二醇呈负相关。盐皮质激素、肾素和 HLA-G 水平之间的关系可能表明肾素-血管紧张素系统在可溶性 HLA-G 表达中的作用。
