Sakthiswary Rajalingham, Shaharir Syahrul, Abdul Wahab Asrul, Uma Rajeswaran Veshaaliini
Faculty of medicine, Universiti Kebangsaan Malaysia, Cheras, Malaysia.
Front Immunol. 2025 Jul 7;16:1607074. doi: 10.3389/fimmu.2025.1607074. eCollection 2025.
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation driven by a complex interplay of autoantibodies, cytokines, and chemokines. While the role of proinflammatory cytokines, such as interleukin-1(IL-1), interleukin-6(IL-6), and tumor necrosis factor-α (TNF-α), in the pathogenesis of RA has been well-established, the contribution of the immunoglobulin G subclass IgG4 remains a topic of ongoing investigation. This cross sectional study aim was to compare the levels of IgG4 and these key inflammatory cytokines in Malaysian patients with RA.
The study enrolled a total of 194 RA patients. All subjects were tested for their serum IgG4, IL-1, IL-6 and TNF-α levels. Besides, subjects were assessed for their disease activity based on DAS28, functional disability based on HAQ-DI (Health Assessment Questionnaire-Disability Index) and the severity of the radiographic joint erosions by using the Modified Sharp Score (MSS).
Correlation analysis revealed a moderate positive association between IgG4 and IL-6 levels (r=0.348, p=0.001), but there were no significant correlations with IL-1 and TNFα levels. IgG4 levels showed a significant positive correlation with DAS28, MSS, and HAQ-DI. All 3 cytokine levels had significant relationships with the DAS28 scores, but for the MSS, only TNF-α (p=0.024) and IL-6 (p=0.016) demonstrated significant associations. None of the cytokines correlated significantly with the HAQ-DI scores.
The positive correlation between IgG4 and IL-6 levels underscores the possibility for IL-6-driven pathways to influence IgG4 production. Serum IgG4 was associated with more clinical aspects of RA compared to the classical inflammatory cytokines.
类风湿性关节炎(RA)是一种自身免疫性疾病,其特征是由自身抗体、细胞因子和趋化因子的复杂相互作用驱动的慢性关节炎症。虽然促炎细胞因子,如白细胞介素-1(IL-1)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)在RA发病机制中的作用已得到充分证实,但免疫球蛋白G亚类IgG4的作用仍是一个正在进行研究的课题。这项横断面研究的目的是比较马来西亚RA患者中IgG4和这些关键炎症细胞因子的水平。
该研究共纳入了194例RA患者。所有受试者均检测了血清IgG4、IL-1、IL-6和TNF-α水平。此外,根据疾病活动评分28(DAS28)评估受试者的疾病活动度,根据健康评估问卷残疾指数(HAQ-DI)评估功能残疾情况,并使用改良夏普评分(MSS)评估放射学关节侵蚀的严重程度。
相关性分析显示IgG4和IL-6水平之间存在中度正相关(r=0.348,p=0.001),但与IL-1和TNFα水平无显著相关性。IgG4水平与DAS28、MSS和HAQ-DI呈显著正相关。所有3种细胞因子水平与DAS28评分均有显著关系,但对于MSS,只有TNF-α(p=0.024)和IL-6(p=0.016)显示出显著相关性。没有一种细胞因子与HAQ-DI评分有显著相关性。
IgG4和IL-6水平之间的正相关强调了IL-6驱动的途径影响IgG4产生的可能性。与经典炎症细胞因子相比,血清IgG4与RA的更多临床方面相关。