Autoantibody screening of plasma and peritoneal fluid of patients with endometriosis

Author:

Laudański Piotr1234ORCID,Rogalska Gabriela5ORCID,Warzecha Damian1,Lipa Michał1,Mańka Grzegorz6,Kiecka Mariusz6,Spaczyński Robert7,Piekarski Piotr8,Banaszewska Beata9,Jakimiuk Artur1011,Issat Tadeusz10,Rokita Wojciech1213,Młodawski Jakub1213,Szubert Maria1415,Sieroszewski Piotr1416,Raba Grzegorz1718,Szczupak Kamil1718,Kluz Tomasz19,Kluza Marek19,Neuman Toomas20,Adler Priit21,Peterson Hedi21,Salumets Andres222324ORCID,Wielgos Miroslaw1

Affiliation:

1. 1st Department of Obstetrics and Gynecology, Medical University of Warsaw , Warsaw, Poland

2. OVIklinika Infertility Center , Warsaw, Poland

3. Women's Health Research Institute, Calisia University , Kalisz, Poland

4. Department of Obstetrics, Gynecology and Gynecological Oncology, Medical University of Warsaw , Warsaw, Poland

5. Clinic of Gynecology, Oncological Gynecology and Obstetrics, Municipal Polyclinical Hospital in Olsztyn , Olsztyn, Poland

6. Angelius Provita Hospital , Katowice, Poland

7. Center for Gynecology, Obstetrics and Infertility Treatment Pastelova , Poznan, Poland

8. Division of Infertility and Reproductive Endocrinology, Department of Gynecology, Obstetrics and Gynecological Oncology, Poznan University of Medical Sciences , Poznan, Poland

9. Chair and Department of Laboratory Diagnostics, Poznan University of Medical Sciences , Poznan, Poland

10. Department of Obstetrics and Gynecology, Institute of Mother and Child , Warsaw, Poland

11. Department of Obstetrics and Gynecology, Central Clinical Hospital of the Ministry of Interior , Warsaw, Poland

12. Collegium Medicum Jan Kochanowski University in Kielce , Kielce, Poland

13. Clinic of Obstetrics and Gynecology, Provincial Combined Hospital in Kielce , Kielce, Poland

14. Department of Gynecology and Obstetrics Medical, University of Lodz , Lodz, Poland

15. Department of Surgical Gynecology and Oncology, Medical University of Lodz , Lodz, Poland

16. Department of Fetal Medicine and Gynecology, Medical University of Lodz , Lodz, Poland

17. Clinic of Obstetric and Gynecology in Przemysl , Przemysl, Poland

18. University of Rzeszow , Rzeszow, Poland

19. Department of Gynecology, Gynecology Oncology and Obstetrics, Institute of Medical Sciences, Medical College of Rzeszow University , Rzeszow, Poland

20. IPDx Diagnostics OY , Tallinn, Estonia

21. Institute of Computer Science, University of Tartu , Tartu, Estonia

22. Competence Centre on Health Technologies , Tartu, Estonia

23. Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu , Tartu, Estonia

24. Division of Obstetrics and Gynaecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute and Karolinska University Hospital , Stockholm, Sweden

Abstract

AbstractSTUDY QUESTIONAre there specific autoantibody profiles in patients with endometriosis that are different from those in controls?SUMMARY ANSWERThis study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients.WHAT IS KNOWN ALREADYVarious inflammatory factors are postulated to be involved in the pathomechanisms of endometriosis, and a potential link exists with autoimmune diseases, which may also play an important role. As the diagnosis of endometriosis remains invasive, it can only be confirmed using laparoscopy with histopathological examination of tissues. Numerous studies have focused on identifying useful biomarkers to confirm the disease, but without unequivocal effects. Autoantibodies are promising molecules that serve as potential prognostic factors.STUDY DESIGN, SIZE, DURATIONA multicentre, cross-sectional study was conducted over 18 months (between 2018 and 2019), at eight Departments of Obstetrics and Gynaecology in several cities across Poland on 137 patients undergoing laparoscopic examination for the diagnosis of endometriosis.PARTICIPANTS/MATERIALS, SETTINGS, METHODSDuring laparoscopy, we obtained plasma samples from 137 patients and peritoneal fluid (PF) samples from 98 patients. Patients with autoimmune diseases were excluded from the study. Autoantibody profiling was performed using HuProt v3.1 human proteome microarrays.MAIN RESULTS AND THE ROLE OF CHANCEWe observed no significant differences in the expression of autoantibodies in the plasma or PF between the endometriosis and control groups. The study revealed that in the PF of women with Stage II endometriosis, compared with other stages, there were significantly higher reactivity signals for ANAPC15 and GABPB1 (adj. P < 0.016 and adj. P < 0.026, respectively; logFC > 1 in both cases). Comparison of the luteal and follicular phases in endometriosis patients revealed that levels of NEIL1 (adj. P < 0.029), MAGEB4 (adj. P < 0.029), and TNIP2 (adj. P < 0.042) autoantibody signals were significantly higher in the luteal phase than in the follicular phase in PF samples of patients with endometriosis. No differences were observed between the two phases of the cycle in plasma or between women with endometriosis and controls. Clustering of PF and plasma samples did not reveal unique autoantibody profiles for endometriosis; however, comparison of PF and plasma in the same patient showed a high degree of concordance.LIMITATIONS, REASONS FOR CAUTIONAlthough this study was performed using the highest-throughput protein array available, it does not cover the entire human proteome and cannot be used to study potentially promising post-translational modifications. Autoantibody levels depend on numerous factors, such as infections; therefore the autoantibody tests should be repeated for more objective results.WIDER IMPLICATIONS OF THE FINDINGSAlthough endometriosis has been linked to different autoimmune diseases, it is unlikely that autoimmune responses mediated by specific autoantibodies play a pivotal role in the pathogenesis of this inflammatory disease. Our study shows that in searching for biomarkers of endometriosis, it may be more efficient to use higher-throughput proteomic microarrays, which may allow the detection of potentially new biomarkers. Only research on such a scale, and possibly with different technologies, can help discover biomarkers that will change the method of endometriosis diagnosis.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by a grant from the Polish Ministry of Health (grant no. 6/6/4/1/NPZ/2017/1210/1352). It was also funded by the Estonian Research Council (grant PRG1076) and the Horizon 2020 Innovation Grant (ERIN; grant no. EU952516), Enterprise Estonia (grant no. EU48695), and MSCA-RISE-2020 project TRENDO (grant no. 101008193). The authors declare that there is no conflict of interest.TRIAL REGISTRATION NUMBERN/A.

Funder

Polish Ministry of Health

Estonian Research Council

Horizon 2020 Innovation

Publisher

Oxford University Press (OUP)

Subject

Obstetrics and Gynecology,Rehabilitation,Reproductive Medicine

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