Division of Rheumatology, Department of Medicine, College of Medicine, Mayo Clinic; 200 First Street SW, Rochester, MN 55905, USA.
Arthritis Res Ther. 2012 Jan 31;14(1):R24. doi: 10.1186/ar3706.
Progression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA.
The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls.
The immune response profile for cytomegalovirus (CMV)/Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, P = 0.018 and r = 0.33, P = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, P < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, P < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-γ, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-γ and IL-13 to CMV/EBV stimulation were associated with greater joint damage.
A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The correlation of this immune response to CMV serology implies possible involvement of latent CMV infection. Therefore, the findings suggest that the immune response to latent CMV infection could play a fundamental role in the progression of inflammation and structural joint damage in patients with RA.
尽管接受了适当的治疗，关节损伤的进展仍然是类风湿关节炎（RA）患者面临的一个重大问题。本研究旨在确定与影像学关节损伤相关的免疫反应特征，作为发现 RA 关节破坏新发病机制的第一步。
该研究纳入了 58 例 RA 患者和 15 名健康对照者。在 48 小时内用 6 种刺激物中的一种或单独在培养基中刺激外周血单核细胞（PBMC），测量细胞因子的释放谱。在多变量调整之前，根据 Sharp-van der Heijde 评分（SHS）将每种刺激物的免疫反应特征与影像学关节损伤相关联。对于与 SHS 相关的特征，根据关节损伤的严重程度评估患者个体细胞因子的分布，并与健康对照组进行比较。
巨细胞病毒（CMV）/EB 病毒（EBV）刺激的免疫反应特征与 SHS 总分和侵蚀评分均相关（r=0.31，P=0.018 和 r=0.33，P=0.011）。调整年龄、性别、病程、自身抗体状态、CMV/EBV 血清学状态、当前疾病活动度、残疾和治疗后，CMV/EBV 免疫反应与 SHS 侵蚀评分的相关性增强（r=0.43，P＜0.003）。CMV/EBV 免疫反应与 CMV IgG 相关（r=0.44，P＜0.001），但与 EBV IgG 无关。CMV/EBV 免疫反应特征最重要的细胞因子是 IFN-γ、IL-2、IL-4、IL-5、IL-13 和 IL-17A，均与 T 细胞免疫有关。CMV/EBV 刺激物的总免疫反应评分以及 IFN-γ和 IL-13 的个体反应均与更大的关节损伤相关。
针对纯化的 CMV/EBV 裂解物的免疫反应特征与影像学关节损伤相关。该免疫反应与 CMV 血清学的相关性提示潜伏性 CMV 感染可能参与其中。因此，研究结果表明，潜伏性 CMV 感染的免疫反应可能在 RA 患者的炎症和结构关节损伤进展中发挥基础性作用。
