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细胞毒性分子作为活动期和非活动期系统性红斑狼疮的潜在生物标志物

Cytotoxic Molecules as Potential Biomarkers for Active and Inactive Systemic Lupus Erythematosus.

作者信息

Santana-Sánchez Paola, Ramírez-Pérez Astrid Asminda, Alberti-Minutti Paolo, Gajón Julián A, Bonifaz Laura C, Sánchez-Escobar Norberto, Legorreta-Haquet María Victoria, Chávez-Sánchez Luis, Chávez-Rueda Adriana Karina

机构信息

Unidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico.

Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Mexico City 14387, Mexico.

出版信息

Biomedicines. 2025 Jun 25;13(7):1559. doi: 10.3390/biomedicines13071559.

Abstract

: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by persistent inflammation. Reliable biomarkers for predicting disease reactivation are lacking. This study aimed to investigate serum cytokines and cytotoxic molecules in both the inactive (iSLE) and active (aSLE) phases to identify potential predictors of disease activity. : Fifty-five SLE patients were classified as having iSLE ( = 36) or aSLE ( = 19) on the basis of clinical parameters and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Serum levels of cytokines, cytotoxic molecules, and CD8 cells were analyzed through flow cytometry and principal component analysis (PCA). Additionally, seventeen healthy donors (HDs) served as a control group. Serum perforin (median: 2219 pg/mL; = 0.0020) and granulysin (median: 1347 pg/mL; = 0.010) levels were significantly higher in patients with aSLE than in patients with iSLE. In contrast, sFas levels were elevated in both SLE groups compared with those in the HD group. Moreover, increased perforin and granulysin levels were correlated with increased SLEDAI-2K scores, and the proportion of cytotoxic cells (CD8granzyme-Bperforin cells) was correlated with disease activity. : The increased levels of cytotoxic molecules and the high CD8 cell proportions suggest that integrating these parameters with traditional biomarkers could enhance disease monitoring and management.

摘要

系统性红斑狼疮(SLE)是一种以持续性炎症为特征的慢性自身免疫性疾病。目前缺乏用于预测疾病复发的可靠生物标志物。本研究旨在调查非活动期(iSLE)和活动期(aSLE)的血清细胞因子和细胞毒性分子,以确定疾病活动的潜在预测指标。55例SLE患者根据临床参数和系统性红斑狼疮疾病活动指数2000(SLEDAI - 2K)被分类为iSLE(n = 36)或aSLE(n = 19)。通过流式细胞术和主成分分析(PCA)分析血清细胞因子、细胞毒性分子和CD8细胞水平。此外,17名健康供体(HDs)作为对照组。aSLE患者的血清穿孔素(中位数:2219 pg/mL;P = 0.0020)和颗粒酶(中位数:1347 pg/mL;P = 0.010)水平显著高于iSLE患者。相比之下,与HD组相比,两个SLE组的sFas水平均升高。此外,穿孔素和颗粒酶水平升高与SLEDAI - 2K评分增加相关,细胞毒性细胞(CD8 + 颗粒酶 - B + 穿孔素细胞)的比例与疾病活动相关。细胞毒性分子水平升高和高CD8细胞比例表明,将这些参数与传统生物标志物相结合可以加强疾病监测和管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114d/12292586/0b9352fea823/biomedicines-13-01559-g001.jpg

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