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多囊卵巢综合征患者的促性腺激素释放激素受体的天然自身抗体。

Natural autoantibodies to the gonadotropin-releasing hormone receptor in polycystic ovarian syndrome.

机构信息

Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

出版信息

PLoS One. 2021 Apr 2;16(4):e0249639. doi: 10.1371/journal.pone.0249639. eCollection 2021.

DOI:10.1371/journal.pone.0249639
PMID:33798258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8018624/
Abstract

CONTEXT

Polycystic ovarian syndrome (PCOS) is a complex disease with different subtypes and unclear etiology. Among the frequent comorbidities are autoimmune diseases, suggesting that autoantibodies (aAb) may be involved in PCOS pathogenesis.

OBJECTIVE

As the gonadal axis often is dysregulated, we tested the hypothesis that aAb to the gonadotropin-releasing hormone receptor (GnRH-R) are of diagnostic value in PCOS.

DESIGN

An in vitro assay for quantifying aAb to the GnRH-R (GnRH-R-aAb) was established by using a recombinant fusion protein of full-length human GnRH-R and firefly luciferase. A commercial rabbit antiserum to human GnRH-R was used for standardization. Serum samples of control subjects and different cohorts of European PCOS patients (n = 1051) were analyzed.

RESULTS

The novel GnRH-R-aAb assay was sensitive, and signals were linear on dilution when tested with the commercial GnRH-R antiserum. Natural GnRH-R-aAb were detected in one control (0.25%) and two PCOS samples (0.31%), and 12 samples were slightly above the threshold of positivity. The identification of samples with positive GnRH-R-aAb was reproducible and the signals showed no matrix interferences.

CONCLUSION

Natural GnRH-R-aAb are present in a very small fraction of adult control and PCOS subjects of European decent. Our results do not support the hypothesis that the GnRH-R constitutes a relevant autoantigen in PCOS.

摘要

背景

多囊卵巢综合征（PCOS）是一种具有不同亚型且病因不明的复杂疾病。其常见合并症包括自身免疫性疾病，这表明自身抗体（aAb）可能参与 PCOS 的发病机制。

目的

由于性腺轴经常失调，我们检验了这样一个假设，即促性腺激素释放激素受体（GnRH-R）的 aAb 在 PCOS 中有诊断价值。

设计

通过使用全长人 GnRH-R 和萤火虫荧光素酶的重组融合蛋白，建立了一种用于定量 GnRH-R-aAb 的体外检测方法。使用针对人 GnRH-R 的商业兔抗血清进行标准化。分析了对照组和不同队列的欧洲 PCOS 患者（n=1051）的血清样本。

结果

该新型 GnRH-R-aAb 检测方法具有较高的灵敏度，并且当使用商业 GnRH-R 抗血清进行测试时，信号在稀释时呈线性。在一个对照（0.25%）和两个 PCOS 样本（0.31%）中检测到天然 GnRH-R-aAb，并且有 12 个样本略微高于阳性阈值。阳性 GnRH-R-aAb 样本的识别是可重复的，且信号没有基质干扰。

结论

天然 GnRH-R-aAb 存在于一小部分欧洲血统的成年对照和 PCOS 受试者中。我们的结果不支持 GnRH-R 是 PCOS 中相关自身抗原的假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d6/8018624/c99b1a0efd3b/pone.0249639.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d6/8018624/929d79d18ae7/pone.0249639.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d6/8018624/51543fef4435/pone.0249639.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d6/8018624/1066bfa0c94a/pone.0249639.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d6/8018624/c99b1a0efd3b/pone.0249639.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d6/8018624/929d79d18ae7/pone.0249639.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d6/8018624/51543fef4435/pone.0249639.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d6/8018624/1066bfa0c94a/pone.0249639.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d6/8018624/c99b1a0efd3b/pone.0249639.g004.jpg

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