Centre for Inflammation Biology & Cancer Immunology, King's College London, London, UK.
Immunology, Leiden University Medical Center, Leiden, Netherlands.
RMD Open. 2023 Dec 20;9(4):e003328. doi: 10.1136/rmdopen-2023-003328.
Undifferentiated, early inflammatory arthritis (EIA) can differentiate into seropositive or seronegative rheumatoid arthritis (RA), peripheral spondyloarthritis (SpA) or remain as seronegative undifferentiated inflammatory arthritis (UIA). Little is known about immune pathways active in the early stages of SpA and seronegative UIA, in contrast to detailed knowledge of seropositive RA. The aim of this study was to examine if specific immune pathways were active in synovial CD4+ and CD8+ T cells in EIA.
Synovial fluid (SF) samples from 30 patients with EIA were analysed for expression of IL-17A, IFNγ and TNFα in CD8+ or CD4+ T cells. Final clinical diagnoses were made at least 12 months after sample collection, by two independent clinicians blind to the study data.
Flow cytometry analysis of all EIA samples indicated considerable variation in synovial IL-17A+CD8+ T cells (Tc17) cell frequencies between patients. The group with a final diagnosis of SpA (psoriatic arthritis or peripheral SpA, n=14) showed a significant enrichment in the percentage of synovial Tc17 cells compared with the group later diagnosed with seronegative UIA (n=10). The small number of patients later diagnosed with seropositive RA (n=6) patients had few Tc17 cells, similar to our previous findings in established disease. In contrast, RA SF contained a significantly higher percentage of CD8+IFNγ+ T cells compared with SpA or seronegative UIA.
These results suggest that adaptive T cell cytokine pathways differ not only between RA and SpA but also seronegative UIA early in the disease process, with a particular activation of Tc17 pathways in early SpA.
未分化的早期炎症性关节炎(EIA)可分化为血清阳性或血清阴性类风湿关节炎(RA)、外周脊柱关节炎(SpA)或保持为血清阴性未分化炎症性关节炎(UIA)。与详细了解血清阳性 RA 不同,对于 SpA 和血清阴性 UIA 早期阶段活跃的免疫途径知之甚少。本研究旨在研究 EIA 中滑膜 CD4+和 CD8+T 细胞中是否存在特定的免疫途径。
分析了 30 例 EIA 患者的滑膜液(SF)样本中 CD8+或 CD4+T 细胞中 IL-17A、IFNγ和 TNFα的表达。在样本采集至少 12 个月后,由两名独立的临床医生对最终临床诊断进行评估,他们对研究数据不知情。
对所有 EIA 样本的流式细胞术分析表明,患者之间滑膜 IL-17A+CD8+T 细胞(Tc17)细胞频率存在很大差异。最终诊断为 SpA(银屑病关节炎或外周 SpA,n=14)的组与后来诊断为血清阴性 UIA(n=10)的组相比,滑膜 Tc17 细胞的百分比显著增加。后来诊断为血清阳性 RA(n=6)的患者数量较少,滑膜 Tc17 细胞数量较少,这与我们之前在已确诊疾病中的发现相似。相比之下,RA SF 中 CD8+IFNγ+T 细胞的百分比明显高于 SpA 或血清阴性 UIA。
这些结果表明,适应性 T 细胞细胞因子途径不仅在 RA 和 SpA 之间不同,而且在疾病早期的血清阴性 UIA 中也不同,早期 SpA 中 Tc17 途径的特定激活。