Souid Moufida, Ghedira Randa, Souissi Sameh, Bouzgarrou Nadia, Gabbouj Sallouha, Shini-Hadhri Salwa, Rhim Mohamed-Saleh, Boukadida Asma, Toumi Dhekra, Faleh Raja, Bouaouina Noureddine, Zakhama Abdelfatteh, Hassen Elham
Molecular Immuno-Oncology Laboratory, Monastir University, Monastir, Tunisia; Higher Institute of Biotechnology of Monastir, Monastir University, Monastir, Tunisia.
Molecular Immuno-Oncology Laboratory, Monastir University, Monastir, Tunisia.
Immunobiology. 2022 Mar;227(2):152189. doi: 10.1016/j.imbio.2022.152189. Epub 2022 Feb 16.
Little is known about the relationship between arginase, an immunosuppressive enzyme, and cervical lesions. The present study is aimed at evaluating arginase activity in plasma and mRNA arginase isoforms expression in cervical cells of patients with abnormal cytology and identifying their relationship with Human papillomavirus (HPV) related parameters such as: HPV type, HPV circulating viral load and anti-HPV16 IgG.
This study included 77 women with cervical lesions and 95 matched controls. Arginase activity was detected by colorimetric assay. Arginase mRNA expression and HPV viral load were evaluated by quantitative real time PCR and anti-HPV16 antibodies were assessed by ELISA.
Compared to controls, the arginase activity was higher among women with cervicitis / low grade squamous intraepithelial lesions (LSIL) (OR: 1.872, 95% CI: 0.833-4.210), and also among women with high-grade squamous intraepithelial lesions (HSIL) / squamous cell carcinoma (SCC) (OR: 3.358, 95% CI: 1.670-8.910). Compared to controls, mRNA expression was significantly upregulated in women with cervical cervicitis and SIL for ARG1, and in women with cancer lesions for ARG2. Arginase activity was positively correlated to ARG2 mRNA expression but not to ARG1. High arginase activity was associated with HPV16, high levels of HPV viral load, and low levels of anti-HPV16 antibodies.
Our findings demonstrated that arginase activity and isoforms expression were enhanced in women with HPV-related precancerous lesions and cervical cancer. Further studies are needed to identify how arginase enzyme induces disease progression and severity.
关于免疫抑制酶精氨酸酶与宫颈病变之间的关系，人们了解甚少。本研究旨在评估细胞学异常患者血浆中的精氨酸酶活性以及宫颈细胞中精氨酸酶亚型的mRNA表达，并确定它们与人类乳头瘤病毒（HPV）相关参数的关系，这些参数包括：HPV类型、HPV循环病毒载量和抗HPV16 IgG。
本研究纳入了77名患有宫颈病变的女性和95名匹配的对照。采用比色法检测精氨酸酶活性。通过定量实时PCR评估精氨酸酶mRNA表达和HPV病毒载量，并通过ELISA评估抗HPV16抗体。
与对照组相比，宫颈炎/低级别鳞状上皮内病变（LSIL）女性的精氨酸酶活性更高（比值比：1.872，95%置信区间：0.833 - 4.210），高级别鳞状上皮内病变（HSIL）/鳞状细胞癌（SCC）女性的精氨酸酶活性也更高（比值比：3.358，95%置信区间：1.670 - 8.910）。与对照组相比，宫颈炎和SIL女性的ARG1 mRNA表达显著上调，癌症病变女性的ARG2 mRNA表达显著上调。精氨酸酶活性与ARG2 mRNA表达呈正相关，但与ARG1无关。高精氨酸酶活性与HPV16、高水平的HPV病毒载量和低水平的抗HPV16抗体相关。
我们的研究结果表明，在患有HPV相关癌前病变和宫颈癌的女性中，精氨酸酶活性和亚型表达增强。需要进一步研究以确定精氨酸酶如何诱导疾病进展和严重程度。
