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评估类风湿关节炎患者 CD40 和 CD40L 的表达情况,及其与临床特征和 DAS28 的相关性。

Assessment of CD40 and CD40L expression in rheumatoid arthritis patients, association with clinical features and DAS28.

机构信息

Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Servicio de Reumatología, O.P.D. Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Jalisco, Mexico.

出版信息

Clin Exp Med. 2019 Nov;19(4):427-437. doi: 10.1007/s10238-019-00568-5. Epub 2019 Jul 16.

Abstract

The predominance of the effector mechanisms by CD4 + T cells is a characteristic of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). The CD40/CD40L costimulatory pathway contributes to these pathogenic mechanisms by promoting autoantibody production and inflammation. Aberrant expression of CD40 and CD40L in RA patients has been shown, the latter prevailing in females. However, contrasting results have emerged regarding the clinical associations of these findings. We determined the association of CD40 and CD40L expression with the clinical activity evaluated through DAS28 in RA patients. A total of 38 female RA patients and 10 age- and sex-matched control subjects were included. CD40 and CD40L mRNA expression was quantified by real-time qPCR, cell surface proteins were determined by flow cytometry, and protein soluble forms were determined by ELISA. The expansion of a CD4 + T cell subpopulation expressing CD40 was identified in the RA group. In addition, high frequencies of CD4 + CD40L + T cells expressing high levels of CD40L, increased levels of sCD40L and overexpression of CD40L mRNA were observed in these patients. Moreover, there was a gradual increase in CD40L when data were stratified according to DAS28, except for very active patients. No correlation was observed between the levels of mRNA, cell surface protein and soluble protein of CD40 and CD40L with the clinical features of RA patients. There is an altered expression of CD40L in female RA patients in association with clinical activity assessed by DAS28, these findings support the evidence that suggests CD40L as a marker of clinical activity.

摘要

CD4+T 细胞效应机制占主导地位是类风湿关节炎(RA)等炎症性自身免疫性疾病的特征。CD40/CD40L 共刺激途径通过促进自身抗体产生和炎症促进这些致病机制。已经表明 RA 患者中存在 CD40 和 CD40L 的异常表达,后者在女性中更为普遍。然而,关于这些发现的临床相关性出现了相互矛盾的结果。我们确定了 CD40 和 CD40L 表达与通过 DAS28 评估的 RA 患者临床活动之间的关联。共纳入 38 名女性 RA 患者和 10 名年龄和性别匹配的对照者。通过实时 qPCR 定量 CD40 和 CD40L 的 mRNA 表达,通过流式细胞术测定细胞表面蛋白,并通过 ELISA 测定可溶性蛋白形式。在 RA 组中鉴定出表达 CD40 的 CD4+T 细胞亚群的扩增。此外,在这些患者中观察到表达高水平 CD40L 的高频率 CD4+CD40L+T 细胞、增加的 sCD40L 水平和 CD40L mRNA 的过表达。此外,当根据 DAS28 对数据进行分层时,除了非常活跃的患者外,CD40L 逐渐增加。CD40 和 CD40L 的 mRNA、细胞表面蛋白和可溶性蛋白水平与 RA 患者的临床特征之间未观察到相关性。在与 DAS28 评估的临床活动相关的女性 RA 患者中存在 CD40L 的改变表达,这些发现支持 CD40L 作为临床活动标志物的证据。

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