类风湿关节炎患者IL-17A、IL-17F和IL-23的研究

IF 0.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Doklady Biochemistry and Biophysics Pub Date : 2025-05-11 DOI:10.1134/S1607672925700139

N A Lapkina, A A Baranov, O P Rechkina, N E Abaytova, S S Zolotavkina, A S Artyukhov, E L Nasonov

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As many as 144 (93.5%) patients were taking DMARDs (methotrexate, leflunamide, and sulfasalazine), as well as nonsteroidal antiinflammatory drugs (NSAIDs) and glucocorticoids (GCs) up to 10 mg/day in terms of prednisolone. The serum levels of IL-17A, IL-17F, and IL-23 were investigated using multiplex xMAR technology. The upper limit of the norm (M+3σ) in 20 sera of healthy donors was 1.78 pg/mL for IL-17A, 9.5 pg/mL for IL-17F, and 91.55 pg/mL for IL-23. RESULTS. : IL-17A (1.16 (0.50; 2.39) pg/mL) and IL-17F (5.02 (1.00; 138.80) pg/mL) concentrations in RA patients were not significantly different from controls (0.78 (0.00; 1.65) pg/mL and 4.02 (1.46; 7.31) pg/mL, p > 0.05). In contrast, IL-23 levels were significantly higher in patients than in donors (21.36 (2.50; 4626.22) pg/mL and 14.63 (0.00; 91.55) pg/mL, p < 0.05). High values of IL-17F (71 patients, 46.1%) and IL-23 (66 patients, 42.9%) were significantly more frequently detected than IL-17A (46 patients, 29.9%: p = 0.003 and p = 0.02, respectively). Overproduction of IL-17A and IL-17F was simultaneously observed in 37 (24.0%) patients, and 32 (20.8%) patients had an increase in IL-17A, IL-17F, and IL-23. Correlations between IL-17A and IL-17F concentrations (r = 0.44, p < 0.05), IL-17A and IL-23 (r = 0.40, p < 0.05), IL-17F and IL-23 (r = 0.94, p < 0.05) were found. No statistically significant differences were found between the concentration of IL-17A, IL-17F, and IL-23 and the frequency of their elevation in RA patients positive or negative for IgM RF, as well as for ACCP. When IL-17A level was elevated, CDAI and SDAI indices and IgM RF concentration were significantly higher than in the comparison group (p < 0.05). 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引用次数: 0

摘要

本研究的目的是确定IL-17A、IL-17F和IL-23在RA晚期患者中的临床和诊断价值。材料与方法：。我们检查了154例根据ACR/EULAR标准可靠诊断为RA的患者（2010年），主要是（73.4%）女性，中年(56.0 (50.0；64.0)年)，病程9.4 (3.0；13.0)岁，放射分期为II期（34.4%）和III期（37.0%），中高活动性(DAS28-ESR 5.40 (4.65；6.00)。其中，83.8%的患者IgM类风湿因子（IgM RF）血清阳性，68.8%的患者有环瓜氨酸肽（ACCP）抗体。多达144例（93.5%）患者正在服用dmard（甲氨蝶呤、来氟酰胺和磺胺嘧啶），以及非甾体类抗炎药（NSAIDs）和糖皮质激素（GCs），以泼尼松龙为例，剂量高达10 mg/天。采用多重xMAR技术检测血清IL-17A、IL-17F和IL-23水平。20例健康供者血清IL-17A、IL-17F和IL-23的正常值（M+3σ）上限分别为1.78 pg/mL、9.5 pg/mL和91.55 pg/mL。结果。： il-17a (1.16; 0.50；2.39) pg/mL)和IL-17F (5.02) (1.00；138.80) pg/mL)在RA患者中的浓度与对照组无显著差异(0.78 (0.00；1.65) pg/mL和4.02 (1.46；7.31) pg/mL, p < 0.05)。相比之下，患者IL-23水平明显高于供者(21.36；4626.22) pg/mL和14.63 (0.00；91.55) pg/mL, p < 0.05)。IL-17F（71例，46.1%）和IL-23（66例，42.9%）的高值检出率明显高于IL-17A（46例，29.9%,p = 0.003和p = 0.02）。在37例（24.0%）患者中同时观察到IL-17A和IL-17F过量产生，32例（20.8%）患者IL-17A、IL-17F和IL-23升高。IL-17A与IL-17F浓度（r = 0.44, p < 0.05）、IL-17A与IL-23浓度（r = 0.40, p < 0.05）、IL-17F与IL-23浓度（r = 0.94, p < 0.05）存在相关性。在IgM RF阳性或阴性以及ACCP阳性的RA患者中，IL-17A、IL-17F和IL-23的浓度及其升高频率之间无统计学差异。IL-17A水平升高时，CDAI、SDAI指数及IgM RF浓度均显著高于对照组（p < 0.05）。在IL-17F分泌过量的患者中，ESR和CRP值高于该指标正常值（p < 0.05）。同时IL-17A浓度与SDAI （r = 0.17, p < 0.05）、IgM RF值（r = 0.19, p < 0.05）、ACCP （r = 0.19, p < 0.05）相关。IL-23高时，HR显著降低（28,p < 0.05），其他疾病活动性指标、IgM RF、ACCP组间差异无统计学意义。同时升高一种、两种或三种细胞因子的患者与浓度正常的患者之间，RA活性的临床和实验室指标均无差异。在疾病晚期的RA患者中，IL-17F的过量产生高于IL-17A的升高频率。RA患者血清IL-23浓度明显高于对照组，其中42.7%的患者血清IL-23浓度偏高。IL-17A和IL-17F的联合生产过剩；IL-17A、IL-17F和IL-23不会增加每个细胞因子的促炎潜能。

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IL-17A, IL-17F, and IL-23 in Patients with Rheumatoid Arthritis.

The aim of the study was to determine the clinical and diagnostic value of IL-17A, IL-17F, and IL-23 in RA patients in the advanced stage of the disease. MATERIALS AND METHODS: . We examined 154 patients with a reliable diagnosis of RA according to ACR/EULAR criteria (2010), predominantly (73.4%) female, middle-aged (56.0 (50.0; 64.0) years), disease duration of 9.4 (3.0; 13.0) years, radiologic stages II (34.4%) and III (37.0%), and moderate to high activity (DAS28-ESR 5.40 (4.65; 6.00). Of these, 83.8% patients were seropositive for IgM rheumatoid factor (IgM RF), and 68.8% had antibodies to cyclic citrullinated peptide (ACCP). As many as 144 (93.5%) patients were taking DMARDs (methotrexate, leflunamide, and sulfasalazine), as well as nonsteroidal antiinflammatory drugs (NSAIDs) and glucocorticoids (GCs) up to 10 mg/day in terms of prednisolone. The serum levels of IL-17A, IL-17F, and IL-23 were investigated using multiplex xMAR technology. The upper limit of the norm (M+3σ) in 20 sera of healthy donors was 1.78 pg/mL for IL-17A, 9.5 pg/mL for IL-17F, and 91.55 pg/mL for IL-23. RESULTS. : IL-17A (1.16 (0.50; 2.39) pg/mL) and IL-17F (5.02 (1.00; 138.80) pg/mL) concentrations in RA patients were not significantly different from controls (0.78 (0.00; 1.65) pg/mL and 4.02 (1.46; 7.31) pg/mL, p > 0.05). In contrast, IL-23 levels were significantly higher in patients than in donors (21.36 (2.50; 4626.22) pg/mL and 14.63 (0.00; 91.55) pg/mL, p < 0.05). High values of IL-17F (71 patients, 46.1%) and IL-23 (66 patients, 42.9%) were significantly more frequently detected than IL-17A (46 patients, 29.9%: p = 0.003 and p = 0.02, respectively). Overproduction of IL-17A and IL-17F was simultaneously observed in 37 (24.0%) patients, and 32 (20.8%) patients had an increase in IL-17A, IL-17F, and IL-23. Correlations between IL-17A and IL-17F concentrations (r = 0.44, p < 0.05), IL-17A and IL-23 (r = 0.40, p < 0.05), IL-17F and IL-23 (r = 0.94, p < 0.05) were found. No statistically significant differences were found between the concentration of IL-17A, IL-17F, and IL-23 and the frequency of their elevation in RA patients positive or negative for IgM RF, as well as for ACCP. When IL-17A level was elevated, CDAI and SDAI indices and IgM RF concentration were significantly higher than in the comparison group (p < 0.05). In patients with IL-17F overproduction, predominance of ESR and CRP values was revealed in comparison with the normal values of this index (p < 0.05). At the same time, IL-17A concentration correlated with SDAI (r = 0.17, p < 0.05), IgM RF values (r = 0.19, p < 0.05), and ACCP (r = 0.19, p < 0.05). When IL-23 values were high, the HR was significantly lower (28, p < 0.05), and the groups did not differ in other indices of disease activity, IgM RF and ACCP. No differences in clinical and laboratory indices of RA activity were found between patients with simultaneous elevation of one, two, or three cytokines and groups of patients with their normal concentrations. In RA patients in the advanced stage of the disease, IL-17F overproduction prevails over the frequency of IL-17A elevation. The concentration of IL-23 in serum is significantly higher in patients with RA compared to the control group, and its high values are found in 42.7% of patients. The combined overproduction of IL-17A and IL-17F; IL-17A, IL-17F, and IL-23 does not increase the proinflammatory potential of each individual cytokine.

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来源期刊

Doklady Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

1.60

自引率

12.50%

发文量

审稿时长

6-12 weeks

期刊介绍： Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.