Petrackova Anna, Horak Pavel, Savara Jakub, Skacelova Martina, Kriegova Eva
Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, Czechia.
Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, Czechia.
Front Immunol. 2024 Dec 18;15:1505615. doi: 10.3389/fimmu.2024.1505615. eCollection 2024.
Glucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood.
We investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23).
Patients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; p < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil-lymphocyte and platelet-lymphocyte ratios and a decreased lymphocyte-monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.
糖皮质激素（GCs）被广泛用于治疗类风湿关节炎（RA），导致长期治疗患者的累积剂量较高。高累积GC剂量对RA全身炎症反应的影响仍知之甚少。
我们通过血细胞计数和92种炎症相关蛋白的血清水平对长期治疗的RA患者（n = 72，中位病程14年）进行了研究，并使用简单疾病活动指数（SDAI）评估疾病活动度。根据累积GC剂量对患者进行分组，临界值为20 g（低/高，n = 49/23）。
与低剂量组相比，活动期RA组中累积GC剂量高的患者血清中23种炎症相关蛋白水平升高（细胞因子/可溶性受体：CCL3、CCL20、CCL25、IL-8、CXCL9、IL-17A、IL-17C、IL-18、sIL-18R1、IL-10、sIL-10RB、OSM和sOPG；生长因子：sTGFα和sHGF；其他炎症介质：半胱天冬酶8、STAMBP、sCDCP1、沉默调节蛋白2、4E-BP1、sCD40、uPA和axin-1；p < 0.05）。在非活动期RA中，高GC组和低GC组的分析血清蛋白水平无差异。此外，与低剂量组相比，活动期RA且GC剂量高的患者白细胞计数增加，中性粒细胞与淋巴细胞及血小板与淋巴细胞的比值增加，淋巴细胞与单核细胞的比值降低（p < 0.05）。这是第一项报告累积GC剂量高的活动期RA患者血清炎症相关蛋白水平升高和血细胞计数失调的研究。全身炎症升高凸显了改善对接受高累积GC剂量患者护理的重要性。
