细胞因子（IL-15、IL-21 和 IFN-γ）与类风湿关节炎：与自身抗体（RF、抗 CCP、抗 MCV 和抗 PADI4）阳性和临床活动的关联。
Cytokines (IL-15, IL-21, and IFN-γ) in rheumatoid arthritis: association with positivity to autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) and clinical activity.
机构信息
Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, No. 950, 44340, Guadalajara, Jalisco, Mexico.
Instituto de Investigación en Ciencias Biomédicas, Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
出版信息
Clin Rheumatol. 2019 Nov;38(11):3061-3071. doi: 10.1007/s10067-019-04681-4. Epub 2019 Jul 17.
INTRODUCTION
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity.
METHODOLOGY
This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI).
RESULTS
The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices.
CONCLUSIONS
Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity. Key Points • IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease. • RF, anti-CCP, and anti-MCV had higher levels in early than established RA. • IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker. • Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15.
简介
类风湿关节炎（RA）是一种以滑膜膜损伤和自身抗体产生为特征的自身免疫性疾病。RA 是一种异质性疾病，其中细胞因子如 IL-15、IL-21 和 IFN-γ 已被关联。然而，它们与自身抗体的关联尚未被清楚描述。本研究的目的是评估细胞因子 IL-15、IL-21 和 IFN-γ 与 RA 中的自身抗体（RF、抗 CCP、抗 MCV 和抗 PADI4）以及疾病活动之间的关系。
方法
本研究纳入了 153 例 RA 患者和 80 例对照（CS）。通过 ELISA 定量检测 IL-15、IL-21、IFN-γ、抗 CCP、抗 MCV 和抗 PADI4 的水平，而 RF 通过比浊法定量。通过疾病活动评分 28-红细胞沉降率（DAS28-ESR）、临床疾病活动指数（CDAI）和简单疾病活动指数（SDAI）评估疾病活动。
结果
与 CS 相比，RA 患者的血清 IL-15、IL-21 和 IFN-γ 以及自身抗体水平升高（p<0.05）。发现 IL-21 与抗 CCP 和抗 MCV 之间存在相关性（p<0.05）。根据 RA 演变，早期 RA 患者的 RF、抗 CCP 和抗 MCV 水平更高。此外，在 RA 血清阳性患者中观察到更高水平的 IL-21。在三个指数评估的中度活动中，观察到两种细胞因子和自身抗体水平均升高。
结论
我们的结果表明，IL-15、IL-21 和 IFN-γ 的可溶性水平升高参与了 RA 中的炎症网络。然而，IL-21 血清水平与更高滴度的自身抗体（RF、抗 CCP 和抗 MCV）相关，而 IL-15 与中度活动相关。关键点 • IL-15、IL-21 和 IFN-y 与 RA 的免疫病理学相关，但与疾病的演变没有显著相关性。 • RF、抗 CCP 和抗 MCV 在早期 RA 中水平高于已建立的 RA。 • IL-21 与 RF、抗 CCP 和抗 MCV 相关，因此可以作为疾病生物标志物提出。 • 中度活动疾病患者的 RF、抗 CCP、抗 MCV 和 IL-15 水平较高。
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