Role of TNF superfamily members lymphotoxin-α, sCD40L, and TNF-α in endometriosis-related infertility

Nanda Yuli Rahmawati, Fadhil Ahsan, Budi Santoso, Alfin Firasy Mufid, A. Sa’adi, S. Dwiningsih, Arif Tunjungseto, M. Y. A. Widyanugraha
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Abstract

TNF-α, LT-α, and sCD40L belong to the TNF superfamily and play a pivotal role in chronic inflammatory disease. Yet, these soluble molecules are largely unexplored in endometriosis cases with infertility. The present study aimed to evaluate serum and peritoneal fluid levels of these molecules and correlate its level to the endometriosis severity. Peripheral blood and peritoneal fluid samples were obtained from 87 infertility cases who underwent laparoscopy, consisting of 44 endometriotic women and 43 non-endometriotic women. The levels of TNF-α, LT-α, and sCD40L were determined using ELISA. Serum and peritoneal TNF-α levels were significantly elevated in the endometriosis group compared to the control group ( p = 0.028; p = 0.027), but not the sCD40L and LT-α level. Serum and peritoneal TNF-α levels were significantly different between late-endometriosis (stage III or IV) compared to the control group ( p = 0.026, p = 0.041, respectively). Moreover, the serum LT-α level was significantly higher in late-endometriosis cases compared to the early-endometriosis (stage I or II) cases ( p = 0.03) and showed a positive correlation with endometriosis rASRM score ( p = 0.001). ROC curve analysis showed a significant diagnostic value of serum LT-α in differentiating the late cases to the early endometriosis patients (AUC = 0.751, p = 0.007). A negative correlation between LT-α and total Endometriosis Fertility Index (EFI) score was also observed ( p = 0.012). Severe endometriosis and lower EFI score are associated with higher serum LT-α level. Serum LT-α is a potential staging biomarker among endometriosis cases. Serum and peritoneal TNF-α levels were elevated in women with severe endometriosis among infertility cases. Further study should address the role and predictive value of LT-α in endometriosis-related infertility.
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TNF 超家族成员淋巴毒素-α、sCD40L 和 TNF-α 在子宫内膜异位症相关不孕症中的作用
TNF-α、LT-α和sCD40L属于TNF超家族,在慢性炎症性疾病中发挥着关键作用。然而,这些可溶性分子在伴有不孕症的子宫内膜异位症病例中大多未得到研究。本研究旨在评估血清和腹腔液中这些分子的水平,并将其水平与子宫内膜异位症的严重程度相关联。本研究采集了87名接受腹腔镜检查的不孕症患者的外周血和腹腔液样本,其中包括44名子宫内膜异位症妇女和43名非子宫内膜异位症妇女。用酶联免疫吸附法测定了 TNF-α、LT-α 和 sCD40L 的水平。与对照组相比,子宫内膜异位症组的血清和腹膜TNF-α水平明显升高(p = 0.028; p = 0.027),但sCD40L和LT-α水平没有升高。与对照组相比,晚期子宫内膜异位症(III期或IV期)患者的血清和腹膜TNF-α水平有显著差异(分别为p = 0.026和p = 0.041)。此外,晚期子宫内膜异位症病例的血清LT-α水平明显高于早期子宫内膜异位症(I期或II期)病例(p = 0.03),且与子宫内膜异位症rASRM评分呈正相关(p = 0.001)。ROC曲线分析显示,血清LT-α在区分晚期和早期子宫内膜异位症患者方面具有显著的诊断价值(AUC = 0.751,p = 0.007)。LT-α与子宫内膜异位症生育指数(EFI)总分之间也呈负相关(p = 0.012)。严重的子宫内膜异位症和较低的 EFI 分数与较高的血清 LT-α 水平相关。血清LT-α是子宫内膜异位症潜在的分期生物标志物。在不孕症病例中,患有严重子宫内膜异位症的妇女血清和腹膜TNF-α水平升高。进一步的研究应探讨LT-α在子宫内膜异位症相关不孕症中的作用和预测价值。
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