Abstract
ContextPolycystic 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.ObjectiveAs 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.DesignAn 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.ResultsThe 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.ConclusionNatural 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.
Highlights
Fertility constitutes an essential issue for both adult males and females
Natural gonadotropin-releasing hormone receptor (GnRH-R)-aAb were detected in one control (0.25%) and two Polycystic ovarian syndrome (PCOS) samples (0.31%), and 12 samples were slightly above the threshold of positivity
Our results do not support the hypothesis that the GnRH-R constitutes a relevant autoantigen in PCOS
Summary
Fertility constitutes an essential issue for both adult males and females. One of the frequent underlying reasons for female infertility is polycystic ovarian syndrome (PCOS), affecting about 5% to 15% of women of reproductive age [2,3,4,5]. The clinical presentation is heterogeneous and established pathognomonic serological markers are missing, hindering a fast and reliable diagnosis [7,8]. Menstrual disturbances such as cycle irregularities are among the first symptoms, and signs of virilisation like hirsutism, a deep voice, acne or alopecia may develop [9,10]. The current diagnosis is based on the Rotterdam criteria from 2003 [3,11], i.e., when any two of the following three criteria are met; i) clinical or biochemical diagnosis of hyperandrogenism, ii) oligo- or amenorrhea (or rather oligo- or anovulation), and/or iii) morphological presence of polycystic ovaries by ultrasound inspection (presence of 12 follicles of 2–9 mm in diameter and/or ovarian volume 10 ml)
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