■抗原呈递树突状细胞(DC)和单核细胞在类风湿性关节炎(RA)发病机理中起重要作用,然而,它们的致耐受性潜力尚不清楚.在这里,在未治疗的RA患者中对DC的致耐受性进行了表征,以确定其在炎性关节炎管理中的作用.
■招募了36名未经治疗的RA患者,根据治疗6个月后的疾病活动评分(DAS),其中62%对甲氨蝶呤(MTX)单药治疗无反应。DC和单核细胞子集频率,激活(CD40,CD86,CD209表达),通过多色流式细胞术检查基线外周血中的致耐受性(细胞内吲哚胺-2,3-双加氧酶[IDO1]和细胞毒性T淋巴细胞抗原4[CTLA-4]表达)。测定血浆中可溶性CTLA-4(sCTLA-4)水平。
■与健康对照组(HC)相比,RA中的DC亚群减少,和常规DC(cDC)的频率与炎症标志物和疾病活动的改善呈负相关。CD141+cDC1s是主要的IDO1表达细胞。与HC相比,RA患者的IDO1+cDC1s减少。IDO1+cDC1s的基线频率与疾病活动的改善呈负相关。与HC相比,RA患者CD1ccDC2s和单核细胞中的CTLA-4表达较低。此外,与MTX无反应者相比,MTX反应者在血浆中具有显著较低的IDO1+cDC1细胞频率和较高水平的sCTLA-4。低IDO1+cDC1细胞有很强的预测性关联,低sCTLA-4和对MTX无反应。
■我们的发现揭示了与RA病理和治疗反应相关的DC和单核细胞免疫表型的改变。致耐受性IDO1+cDC1s的频率和低水平的sCTLA-4与MTX无反应性和治疗结果密切相关。这些结果表明,研究IDO1cDC1和sCTLA-4与治疗反应的相关性可能更适用于其他自身免疫性疾病。
UNASSIGNED: Antigen-presenting dendritic cells (DCs) and monocytes play an essential role in rheumatoid arthritis (RA) pathogenesis, however, their tolerogenic potential remains unclear. Herein, the tolerogenic profiles of DCs are characterized in treatment-naïve RA patients to determine their role to inflammatory arthritis management.
UNASSIGNED: Thirty-six treatment-naïve RA patients were enrolled, of which 62% were non-responders to methotrexate (MTX) monotherapy based on disease activity score (DAS) after 6-months of therapy. DC and monocyte subset frequencies, activation (CD40, CD86, CD209 expression), and tolerogenic profile (intracellular indoleamine-2,3-dioxygenase [IDO1] and cytotoxic T lymphocyte antigen 4 [CTLA-4] expression) were examined in the baseline peripheral blood by multicolor flow-cytometry. Soluble CTLA-4 (sCTLA-4) levels in plasma were measured.
UNASSIGNED: DC subsets were decreased in RA compared to healthy controls (HC), and the frequency of conventional DCs (cDC) inversely correlated with inflammatory markers and improvement in disease activity. CD141+ cDC1s were the major IDO1-expressing cells. IDO1+cDC1s were reduced in RA patients compared to HC. The baseline frequency of IDO1+cDC1s inversely correlated with improvement in disease activity. CTLA-4 expression in CD1c+ cDC2s and monocytes was lower in RA patients compared to HC. Moreover, MTX-responders had a significantly lower frequency of IDO1+cDC1 cells and higher level of sCTLA-4 in the plasma compared to MTX non-responders. There was a strong predictive association of low IDO1+cDC1 cells, low sCTLA-4 and non-response to MTX.
UNASSIGNED: Our findings reveal altered DC and monocytes immunophenotypes that are associated with RA pathology and treatment response. The frequencies of tolerogenic IDO1+cDC1s and the low level of sCTLA-4 are strongly associated with MTX non-responsiveness and therapeutic outcome. These results suggest that investigation of the association IDO1+cDC1 and sCTLA-4 with response to treatment may be more generalizable to other autoimmune diseases.