Department of Immunology, Landspitali University Hospital, Reykjavík, Iceland.
Department of Rheumatology, Landspitali University Hospital, Reykjavik, Iceland.
Scand J Immunol. 2022 Jan;95(1):e13116. doi: 10.1111/sji.13116. Epub 2021 Nov 24.
Rheumatoid arthritis (RA) is a chronic multisystem disease with a complex immunopathology. Its inflammatory state is dominated by pro-inflammatory cytokines such as TNFα and activated Th1/Th17. Only proportion of patients achieve clinical remission despite potent biologics targeting these pathways. This study investigated the resolution of inflammation in RA patients (naïve for biologics) receiving TNFα inhibitors (TNFi) and evaluated the biological mechanisms behind treatment response and assessed them using clinical scoring systems. The majority showed a good clinical response after six months (6M) and a significant drop in DAS28-CRP (P ≤ .002), CDAI (P ≤ .0001) and RheumXpert (P ≤ .0001). Before treatment, the patients demonstrated a chronic innate and adaptive inflammatory state. The improved clinical condition was reflected with a decrease in Th17/Tc17 (P ≤ .05) and an increase in Tregs after 6M (P ≤ .05). Using a logistic regression model on serum data, IL-6, IL-18, IL-21, IL-22, IFNγ and TNFα were identified as the main contributing biomarkers in the chronic inflammatory state of RA. A specific test score (STS) was defined and converted to a single cytokine composite test score (CCTS), which showed the disease outcome on a scale 0-100, providing sensitivity and specificity of ≥90%. Thus, the immunological complexity in RA is driven by a complex interplay of pro-inflammatory cytokines and effector T-cell response dominated by Th17/Tc17. In addition, the resolution of inflammation could be linked to a partially Treg-driven homeostatic innate immune response. Therefore, a more complex therapeutic approach against the above markers might be of value to obtain full clinical remission in the future.
类风湿关节炎（RA）是一种慢性多系统疾病，具有复杂的免疫病理学。其炎症状态以 TNFα 和激活的 Th1/Th17 等促炎细胞因子为主。尽管针对这些途径的生物制剂具有强大的作用，但只有一部分患者达到临床缓解。本研究调查了接受 TNFα 抑制剂（TNFi）的 RA 患者（无生物制剂治疗史）炎症的消退情况，并评估了治疗反应背后的生物学机制，使用临床评分系统进行了评估。大多数患者在 6 个月时（6M）表现出良好的临床反应，DAS28-CRP（P≤.002）、CDAI（P≤.0001）和 RheumXpert（P≤.0001）显著下降。治疗前，患者表现出慢性固有和适应性炎症状态。经过 6 个月的治疗，Th17/Tc17 减少（P≤.05），Tregs 增加（P≤.05），改善了临床状况。使用血清数据的逻辑回归模型，确定了 IL-6、IL-18、IL-21、IL-22、IFNγ 和 TNFα 是 RA 慢性炎症状态的主要贡献生物标志物。定义了一个特定的测试评分（STS）并转换为单个细胞因子综合测试评分（CCTS），该评分在 0-100 范围内显示疾病结果，提供了≥90%的敏感性和特异性。因此，RA 中的免疫复杂性是由促炎细胞因子和以 Th17/Tc17 为主的效应 T 细胞反应的复杂相互作用驱动的。此外，炎症的消退可能与部分 Treg 驱动的固有免疫反应有关。因此，针对上述标志物的更复杂的治疗方法可能在未来获得完全临床缓解方面具有价值。
