Increased testosterone and proinflammatory cytokines in patients with polycystic ovary syndrome correlate with elevated GnRH receptor autoantibody activity assessed by a fluorescence resonance energy transfer-based bioassay.
Increased testosterone and proinflammatory cytokines in patients with polycystic ovary syndrome correlate with elevated GnRH receptor autoantibody activity assessed by a fluorescence resonance energy transfer-based bioassay.
复制标题
DOI：
10.1007/s12020-021-02761-7
复制
发表时间：
2021-10
期刊：
影响因子：
3.7
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Li H;Guo Y;Deng J;Fischer H;Weedin EA;Burks HR;Craig LB;Yu X
最近发现的促性腺激素释放激素受体（GnRHR）激动性自身抗体（AAb）是多囊卵巢综合征（PCOS）的新研究和治疗靶点。在这项研究中，我们使用一种新的基于细胞的荧光共振能量转移 (FRET) 生物测定法来分析 PCOS 患者血清 GnRHR-AAb 活性，并检查其与睾酮和促炎细胞因子的关系。通过基于 FRET 的生物测定和基于多重微珠的免疫测定，分别测试了 33 名 PCOS 患者、39 名非 PCOS 排卵性不孕对照者和 30 名正常对照者的血清样本的 GnRHR-AAb 活性和促炎细胞因子。使用 Spearman 相关性检验分析相关性。 PCOS 患者的血清 GnRHR-AAb 活性显着高于排卵不孕对照 (p < 0.05) 和正常对照 (p < 0.01)。 39% 的 PCOS 患者、10% 的排卵不孕对照者和 0% 的正常对照者 GnRHR-AAb 呈阳性。 PCOS IgG 诱导的 GnRHR 激活可被 GnRHR 拮抗剂西曲瑞克特异性阻断。与排卵性不孕症和正常对照相比，PCOS 患者促炎细胞因子白细胞介素 2、白细胞介素 6、干扰素 γ 和肿瘤坏死因子 α 的血清水平显着升高（p < 0.01）。相关分析表明，PCOS 组中 GnRHR-AAb 活性与睾酮和促炎细胞因子水平呈正相关。通过新的 FRET 测定评估，GnRHR-AAb 活性升高与 PCOS 中睾酮和促炎细胞因子的增加有关，表明 GnRHR 的自身免疫激活可能导致这种常见疾病的发病机制。
The recently identified agonistic autoantibodies (AAb) to the gonadotropin-releasing hormone receptor (GnRHR) are a novel investigative and therapeutic target for polycystic ovary syndrome (PCOS). In this study, we used a new cell-based fluorescence resonance energy transfer (FRET) bioassay to analyze serum GnRHR-AAb activity and examine its relationship with testosterone and proinflammatory cytokines in patients with PCOS. Serum samples from 33 PCOS patients, 39 non-PCOS ovulatory infertile controls and 30 normal controls were tested for GnRHR-AAb activity and proinflammatory cytokines in a FRET-based bioassay and multiplex bead-based immunoassay, respectively. Correlation was analyzed using the Spearman’s correlation test. Serum GnRHR-AAb activity was significantly higher in the PCOS patients than for the ovulatory infertile (p < 0.05) and normal (p < 0.01) controls. GnRHR-AAb were positive in 39% of PCOS patients, 10% of ovulatory infertile controls, and 0% of normal controls. PCOS IgG-induced GnRHR activation was specifically blocked by the GnRHR antagonist cetrorelix. Serum levels of proinflammatory cytokines interleukin-2, interleukin-6, interferon-γ and tumor necrosis factor-α were significantly increased in PCOS patients compared with ovulatory infertile and normal controls (p < 0.01). Correlation analysis demonstrated positive correlations of GnRHR-AAb activity with testosterone and proinflammatory cytokine levels in the PCOS group. Elevated GnRHR-AAb activity, as assessed by a new FRET assay, is associated with increased testosterone and proinflammatory cytokines in PCOS, suggesting autoimmune activation of GnRHR may contribute to the pathogenesis of this common disorder.
登录
查看更多内容
影响因子：
3.1
作者：
Meyer, Carlotta;Heidecke, Harald
通讯作者：
Heidecke, Harald
影响因子：
3.1
作者：
Ojeda-Ojeda, Miriam;Murri, Mora;Escobar-Morreale, Hector F.
通讯作者：
Escobar-Morreale, Hector F.
DOI：
10.1161/hypertensionaha.114.05037
发表时间：
2015-04
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Li H;Kem DC;Zhang L;Huang B;Liles C;Benbrook A;Gali H;Veitla V;Scherlag BJ;Cunningham MW;Yu X
通讯作者：
Yu X
影响因子：
5.8
作者：
Chen, HF;Jeung, EB;Leung, PCK
通讯作者：
Leung, PCK
影响因子：
6.7
作者：
Dragun, Duska;Philippe, Aurelie;Hegner, Bjoern
通讯作者：
Hegner, Bjoern