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子宫内膜异位症患者血浆和腹腔液的自身抗体筛查。

Autoantibody screening of plasma and peritoneal fluid of patients with endometriosis.

作者信息

Laudański Piotr, Rogalska Gabriela, Warzecha Damian, Lipa Michał, Mańka Grzegorz, Kiecka Mariusz, Spaczyński Robert, Piekarski Piotr, Banaszewska Beata, Jakimiuk Artur, Issat Tadeusz, Rokita Wojciech, Młodawski Jakub, Szubert Maria, Sieroszewski Piotr, Raba Grzegorz, Szczupak Kamil, Kluz Tomasz, Kluza Marek, Neuman Toomas, Adler Priit, Peterson Hedi, Salumets Andres, Wielgos Miroslaw

机构信息

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

OVIklinika Infertility Center, Warsaw, Poland.

出版信息

Hum Reprod. 2023 Apr 3;38(4):629-643. doi: 10.1093/humrep/dead011.

Abstract

STUDY QUESTION

Are there specific autoantibody profiles in patients with endometriosis that are different from those in controls?

SUMMARY ANSWER

This study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients.

WHAT IS KNOWN ALREADY

Various 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, DURATION: A 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, METHODS: During 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 CHANCE

We 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 CAUTION: Although 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 FINDINGS

Although 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 NUMBER

N/A.

摘要

研究问题

子宫内膜异位症患者是否存在与对照组不同的特定自身抗体谱?

总结答案

本研究未发现所研究患者组中自身抗体的患病率显著更高。

已知信息

各种炎症因子被认为参与子宫内膜异位症的发病机制,并且与自身免疫性疾病存在潜在联系,自身免疫性疾病可能也起重要作用。由于子宫内膜异位症的诊断仍然具有侵入性,只能通过腹腔镜检查并对组织进行组织病理学检查来确诊。许多研究致力于寻找有用的生物标志物以确诊该疾病,但效果并不明确。自身抗体是有前景的分子,可作为潜在的预后因素。

研究设计、规模、持续时间:一项多中心横断面研究在18个月内(2018年至2019年)进行,在波兰多个城市的8个妇产科进行,研究对象为137例接受腹腔镜检查以诊断子宫内膜异位症的患者。

参与者/材料、环境、方法:在腹腔镜检查期间,我们从137例患者中获取血浆样本,从98例患者中获取腹腔液(PF)样本。患有自身免疫性疾病的患者被排除在研究之外。使用HuProt v3.1人类蛋白质组微阵列进行自身抗体谱分析。

主要结果及偶然性的作用

我们观察到子宫内膜异位症组与对照组之间血浆或PF中自身抗体的表达无显著差异。研究表明,在II期子宫内膜异位症女性的PF中,与其他阶段相比,ANAPC15和GABPB1的反应性信号显著更高(校正P值分别<0.016和<0.026;两种情况下logFC>1)。对子宫内膜异位症患者黄体期和卵泡期的比较显示,在子宫内膜异位症患者的PF样本中,NEIL1(校正P值<0.029)、MAGEB4(校正P值<0.029)和TNIP2(校正P值<0.042)自身抗体信号在黄体期显著高于卵泡期。在血浆的两个周期阶段之间或子宫内膜异位症女性与对照组之间未观察到差异。PF和血浆样本的聚类未揭示子宫内膜异位症独特的自身抗体谱;然而,同一患者的PF和血浆比较显示出高度一致性。

局限性、注意事项:尽管本研究使用了可用的最高通量蛋白质阵列进行,但它并未涵盖整个人类蛋白质组,也不能用于研究潜在有前景的翻译后修饰。自身抗体水平取决于多种因素,如感染;因此,为了获得更客观的结果,应重复进行自身抗体检测。

研究结果的更广泛影响

尽管子宫内膜异位症与不同的自身免疫性疾病有关,但由特定自身抗体介导的自身免疫反应不太可能在这种炎症性疾病的发病机制中起关键作用。我们的研究表明,在寻找子宫内膜异位症的生物标志物时,使用更高通量的蛋白质组微阵列可能更有效,这可能有助于检测潜在的新生物标志物。只有如此规模的研究,可能还需采用不同技术,才能有助于发现能改变子宫内膜异位症诊断方法的生物标志物。

研究资金/利益冲突:本研究由波兰卫生部的一项拨款资助(拨款编号6/6/4/1/NPZ/2017/1210/1352)。它还由爱沙尼亚研究委员会(拨款PRG1076)、地平线2020创新拨款(ERIN;拨款编号EU****)、爱沙尼亚企业局(拨款编号EU48695)以及MSCA - RISE - 2020项目TRENDO(拨款编号101008193)资助。作者声明不存在利益冲突。

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