Natural Autoantibodies to the Gonadotropin-releasing Hormone Receptor in Polycystic Ovarian Syndrome

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2021 Apr 2

PMID 33798258

Citations 5

Authors

Lisa-Marie Sattler

Hanna A Schniewind

Waldemar B Minich

Christoph W Haudum

Petra Niklowitz

Julia Munzker

Gabor L Kovacs

Thomas Reinehr

Barbara Obermayer-Pietsch

Lutz Schomburg

Affiliations

Soon will be listed here.

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.

Citing Articles

Unveiling the link: anti-protein disulfide isomerase A3 autoantibody expression and polycystic ovary syndrome risk in euthyroid autoimmune thyroiditis women.

Chen Z, Zhang C, Meng C, Hu Y, Niu Y, Gao B J Ovarian Res. 2024; 17(1):247.

PMID: 39702372 PMC: 11656784. DOI: 10.1186/s13048-024-01569-z.

Aberrant HPO Axis Alterations and Autoimmune Abnormalities in PCOS Patients with DOR: A Retrospective Analysis.

Geng X, He Z, Bao Z, Di W, Gu Z J Clin Med. 2023; 12(16).

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Antibodies to SARS-CoV-2 in follicular fluids and their association with assisted reproduction.

Chillon T, Weiss G, Demircan K, Minich W, Schenk M, Schomburg L Front Immunol. 2023; 14:1120328.

PMID: 37006276 PMC: 10064043. DOI: 10.3389/fimmu.2023.1120328.

Autoimmunity to Sphingosine-1-Phosphate-Receptors in Systemic Sclerosis and Pulmonary Arterial Hypertension.

Gluschke H, Siegert E, Minich W, Hackler J, Riemekasten G, Kuebler W Front Immunol. 2022; 13:935787.

PMID: 35860272 PMC: 9289471. DOI: 10.3389/fimmu.2022.935787.

Autoimmunity to the Follicle-Stimulating Hormone Receptor (FSHR) and Luteinizing Hormone Receptor (LHR) in Polycystic Ovarian Syndrome.

Schniewind H, Sattler L, Haudum C, Munzker J, Minich W, Obermayer-Pietsch B Int J Mol Sci. 2021; 22(24).

PMID: 34948471 PMC: 8706343. DOI: 10.3390/ijms222413667.

References

Petrikova J, Lazurova I . Ovarian failure and polycystic ovary syndrome. Autoimmun Rev. 2011; 11(6-7):A471-8. DOI: 10.1016/j.autrev.2011.11.010. View

Endo T, Kogai T, Nakazato M, Saito T, Kaneshige M, Onaya T . Autoantibody against Na+/I- symporter in the sera of patients with autoimmune thyroid disease. Biochem Biophys Res Commun. 1996; 224(1):92-5. DOI: 10.1006/bbrc.1996.0989. View

Glintborg D, Andersen M . Medical comorbidity in polycystic ovary syndrome with special focus on cardiometabolic, autoimmune, hepatic and cancer diseases: an updated review. Curr Opin Obstet Gynecol. 2017; 29(6):390-396. DOI: 10.1097/GCO.0000000000000410. View

March W, Moore V, Willson K, Phillips D, Norman R, Davies M . The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2009; 25(2):544-51. DOI: 10.1093/humrep/dep399. View

Hefler-Frischmuth K, Walch K, Huebl W, Baumuehlner K, Tempfer C, Hefler L . Serologic markers of autoimmunity in women with polycystic ovary syndrome. Fertil Steril. 2009; 93(7):2291-4. DOI: 10.1016/j.fertnstert.2009.01.056. View

Engmann L, Jin S, Sun F, Legro R, Polotsky A, Hansen K . Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype. Am J Obstet Gynecol. 2017; 216(5):493.e1-493.e13. PMC: 5420474. DOI: 10.1016/j.ajog.2017.01.003. View

Boivin J, Bunting L, Collins J, Nygren K . International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007; 22(6):1506-12. DOI: 10.1093/humrep/dem046. View

Brown R, Joseph J, Cochran E, Gewert C, Semple R, Gorden P . Type B Insulin Resistance Masquerading as Ovarian Hyperthecosis. J Clin Endocrinol Metab. 2016; 102(6):1789-1791. PMC: 5470776. DOI: 10.1210/jc.2016-3674. View

Boege F, Westenfeld R, Jahns R . βAAb Determined by Peptide ELISA: A Signal in the Noise?. J Am Coll Cardiol. 2017; 70(6):807-808. DOI: 10.1016/j.jacc.2017.03.617. View

10.

Alborzi S, Tavazoo F, Samsami Dehaghani A, Ghaderi A, Alborzi S, Alborzi M . Determination of antiovarian antibodies after laparoscopic ovarian electrocauterization in patients with polycystic ovary syndrome. Fertil Steril. 2008; 91(4):1159-63. DOI: 10.1016/j.fertnstert.2008.01.038. View

11.

Munzker J, Hofer D, Trummer C, Ulbing M, Harger A, Pieber T . Testosterone to dihydrotestosterone ratio as a new biomarker for an adverse metabolic phenotype in the polycystic ovary syndrome. J Clin Endocrinol Metab. 2014; 100(2):653-60. DOI: 10.1210/jc.2014-2523. View

12.

Schwiebert C, Kuhnen P, Becker N, Welsink T, Keller T, Minich W . Antagonistic Autoantibodies to Insulin-Like Growth Factor-1 Receptor Associate with Poor Physical Strength. Int J Mol Sci. 2020; 21(2). PMC: 7013472. DOI: 10.3390/ijms21020463. View

13.

Bednarska S, Siejka A . The pathogenesis and treatment of polycystic ovary syndrome: What's new?. Adv Clin Exp Med. 2017; 26(2):359-367. DOI: 10.17219/acem/59380. View

14.

Goudswaard J, van der Donk J, Noordzij A, Van Dam R, Vaerman J . Protein A reactivity of various mammalian immunoglobulins. Scand J Immunol. 1978; 8(1):21-8. DOI: 10.1111/j.1365-3083.1978.tb00492.x. View

15.

Wang J, Wu D, Guo H, Li M . Hyperandrogenemia and insulin resistance: The chief culprit of polycystic ovary syndrome. Life Sci. 2019; 236:116940. DOI: 10.1016/j.lfs.2019.116940. View

16.

Lass N, Kleber M, Winkel K, Wunsch R, Reinehr T . Effect of lifestyle intervention on features of polycystic ovarian syndrome, metabolic syndrome, and intima-media thickness in obese adolescent girls. J Clin Endocrinol Metab. 2011; 96(11):3533-40. DOI: 10.1210/jc.2011-1609. View

17.

Kem D, Li H, Yu X, Weedin E, Reynolds A, Forsythe E . The Role of GnRH Receptor Autoantibodies in Polycystic Ovary Syndrome. J Endocr Soc. 2020; 4(8):bvaa078. PMC: 7417878. DOI: 10.1210/jendso/bvaa078. View

18.

Zophel K, Roggenbuck D, Schott M . Clinical review about TRAb assay's history. Autoimmun Rev. 2010; 9(10):695-700. DOI: 10.1016/j.autrev.2010.05.021. View

19.

Davies T, Andersen S, Latif R, Nagayama Y, Barbesino G, Brito M . Graves' disease. Nat Rev Dis Primers. 2020; 6(1):52. DOI: 10.1038/s41572-020-0184-y. View

20.

Becker N, Muller J, Gottel P, Wallukat G, Schimke I . Cardiomyopathy - An approach to the autoimmune background. Autoimmun Rev. 2017; 16(3):269-286. DOI: 10.1016/j.autrev.2017.01.012. View