{"title":"[Regulatory effect of lactate on peripheral blood CD4<sup>+</sup> T cell subsets in patients with rheumatoid arthritis].","authors":"Huina Huang, Jing Zhao, Xiangge Zhao, Ziran Bai, Xia Li, Guan Wang","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the serum lactate level in patients with rheumatoid arthritis (RA) and its relationship with disease activity, and to analyze the effect of sodium lactate on the activation of CD4<sup>+</sup> T cells, the ability of secreting cytokines and CD4<sup>+</sup>T cell subsets in peripheral blood of the RA patients.</p><p><strong>Methods: </strong>The peripheral blood of healthy controls (HC) and RA patients was collected, and the content of lactate in the supernatant was detected by lactate detection kit, the correlation between the content of lactate and the disease score of the RA patients was analyzed; the activation level of CD4<sup>+</sup> T cells, the proportion of CD4<sup>+</sup> T cell subsets and the cytokines secreted by CD4<sup>+</sup> T cells in peripheral blood of all the RA patients were detected by flow cytometry after being stimulated with sodium lactate.</p><p><strong>Results: </strong>The serum lactate level in the RA patients (<i>n</i>=66) was significantly higher than that in the HC (<i>n</i>=60, <i>P</i> < 0.001), and there was a certain correlation with disease activity score in 28 joints (DAS28)-C-reactive protein (CRP) (<i>r</i>=0.273, <i>P</i>=0.029), The levels of rheumatoid factor [RF, 197.50 (26.03, 783.00) IU/mL <i>vs.</i> 29.30 (0.00, 102.60) IU/mL, <i>P</i> < 0.01], CRP [37.40 (11.30, 72.60) mg/L <i>vs.</i> 5.83 (2.36, 12.45) mg/L, <i>P</i> < 0.001], were increased in patients with the lactate concentration greater than 5 mmol/L were significantly higher than those in patients with the lactate concentration less than or equal 5 mmol/L, however, there was no significant difference in the expression of erythrocyte sedimentation rate [ESR, 42.00 (19.00, 77.00) mm/h <i>vs.</i> 25.00 (12.50, 45.50) mm/h, <i>P</i>>0.05] and anti-cyclic citrullinated peptied (CCP) antibody [82.35 (17.70, 137.00) RU/mL <i>vs.</i> 68.60 (25.95, 119.70) RU/mL, <i>P</i>>0.05]. Compared with the control group, the expression of PD-1 (46.15%±8.54% <i>vs.</i> 41.67%±9.98%, <i>P</i> < 0.001), inducible costimulatory molecule (ICOS, 5.77%±8.60% <i>vs.</i> 18.65%±7.94%, <i>P</i> < 0.01) and CD25 (25.89%±5.80% <i>vs.</i> 22.25%±4.59%, <i>P</i> < 0.01) on the surface of CD4<sup>+</sup> T cells in the RA patients treated with sodium lactate was significantly increased. Compared with the control group, the proportion of Th17 (4.62%±1.74% <i>vs.</i> 2.93%±1.92%, <i>P</i> < 0.05) and Tph (28.02%±6.28% <i>vs.</i> 20.32%±5.82%, <i>P</i> < 0.01) cells in CD4<sup>+</sup>T cells of the RA patients in the sodium lactate treatment group increased. Compared with the control group, the expression of IL-21 (5.73%±1.59% <i>vs.</i> 4.75%±1.71%, <i>P</i> < 0.05) in CD4<sup>+</sup>T cells was up-regulated in the RA patients treated with sodium lactate.</p><p><strong>Conclusion: </strong>The level of serum lactate in RA patients is increased, which promotes the activation of CD4<sup>+</sup>T cells and the secretion of IL-21, and up-regulates the proportion of Th17 and Tph cells in the RA patients.</p>","PeriodicalId":8790,"journal":{"name":"北京大学学报(医学版)","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167554/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"北京大学学报(医学版)","FirstCategoryId":"3","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: To investigate the serum lactate level in patients with rheumatoid arthritis (RA) and its relationship with disease activity, and to analyze the effect of sodium lactate on the activation of CD4+ T cells, the ability of secreting cytokines and CD4+T cell subsets in peripheral blood of the RA patients.
Methods: The peripheral blood of healthy controls (HC) and RA patients was collected, and the content of lactate in the supernatant was detected by lactate detection kit, the correlation between the content of lactate and the disease score of the RA patients was analyzed; the activation level of CD4+ T cells, the proportion of CD4+ T cell subsets and the cytokines secreted by CD4+ T cells in peripheral blood of all the RA patients were detected by flow cytometry after being stimulated with sodium lactate.
Results: The serum lactate level in the RA patients (n=66) was significantly higher than that in the HC (n=60, P < 0.001), and there was a certain correlation with disease activity score in 28 joints (DAS28)-C-reactive protein (CRP) (r=0.273, P=0.029), The levels of rheumatoid factor [RF, 197.50 (26.03, 783.00) IU/mL vs. 29.30 (0.00, 102.60) IU/mL, P < 0.01], CRP [37.40 (11.30, 72.60) mg/L vs. 5.83 (2.36, 12.45) mg/L, P < 0.001], were increased in patients with the lactate concentration greater than 5 mmol/L were significantly higher than those in patients with the lactate concentration less than or equal 5 mmol/L, however, there was no significant difference in the expression of erythrocyte sedimentation rate [ESR, 42.00 (19.00, 77.00) mm/h vs. 25.00 (12.50, 45.50) mm/h, P>0.05] and anti-cyclic citrullinated peptied (CCP) antibody [82.35 (17.70, 137.00) RU/mL vs. 68.60 (25.95, 119.70) RU/mL, P>0.05]. Compared with the control group, the expression of PD-1 (46.15%±8.54% vs. 41.67%±9.98%, P < 0.001), inducible costimulatory molecule (ICOS, 5.77%±8.60% vs. 18.65%±7.94%, P < 0.01) and CD25 (25.89%±5.80% vs. 22.25%±4.59%, P < 0.01) on the surface of CD4+ T cells in the RA patients treated with sodium lactate was significantly increased. Compared with the control group, the proportion of Th17 (4.62%±1.74% vs. 2.93%±1.92%, P < 0.05) and Tph (28.02%±6.28% vs. 20.32%±5.82%, P < 0.01) cells in CD4+T cells of the RA patients in the sodium lactate treatment group increased. Compared with the control group, the expression of IL-21 (5.73%±1.59% vs. 4.75%±1.71%, P < 0.05) in CD4+T cells was up-regulated in the RA patients treated with sodium lactate.
Conclusion: The level of serum lactate in RA patients is increased, which promotes the activation of CD4+T cells and the secretion of IL-21, and up-regulates the proportion of Th17 and Tph cells in the RA patients.
目的研究类风湿性关节炎(RA)患者血清乳酸水平及其与疾病活动性的关系,分析乳酸钠对RA患者外周血CD4+T细胞活化、细胞因子分泌能力及CD4+T细胞亚群的影响:收集健康对照组(HC)和RA患者的外周血,用乳酸检测试剂盒检测上清液中乳酸的含量,分析乳酸含量与RA患者疾病评分的相关性;用流式细胞术检测所有RA患者外周血中经乳酸钠刺激后的CD4+T细胞的活化水平、CD4+T细胞亚群的比例及CD4+T细胞分泌的细胞因子:结果:RA 患者的血清乳酸水平(n=66)明显高于 HC 患者(n=60,P <0.001),且与 28 个关节的疾病活动度评分(DAS28)-C 反应蛋白(CRP)有一定的相关性(r=0.类风湿因子[RF,197.50(26.03,783.00)IU/mL vs. 29.30(0.00,102.60)IU/mL,P<0.01]、CRP[37.40(11.30,72.60)mg/L vs. 5.83(2.36,12.45)mg/L,P<0.001],乳酸浓度大于5 mmol/L的患者明显高于乳酸浓度小于等于5 mmol/L的患者,但红细胞沉降率[ESR,42.00 (19.00, 77.00) mm/h vs. 25.00 (12.50, 45.50) mm/h,P>0.05]和抗环瓜氨酸肽(CCP)抗体[82.35 (17.70, 137.00) RU/mL vs. 68.60 (25.95, 119.70) RU/mL,P>0.05]的表达无明显差异。与对照组相比,PD-1(46.15%±8.54% vs. 41.67%±9.98%, P < 0.001)、诱导性成本刺激分子(ICOS, 5.77%±8.60% vs. 18.65%±7.94%,P<0.01)和CD25(25.89%±5.80% vs. 22.25%±4.59%,P<0.01)在乳酸钠治疗的RA患者的CD4+T细胞表面明显增加。与对照组相比,乳酸钠治疗组 RA 患者 CD4+T 细胞中 Th17(4.62%±1.74% vs. 2.93%±1.92%,P<0.05)和 Tph(28.02%±6.28% vs. 20.32%±5.82%,P<0.01)细胞比例增加。与对照组相比,乳酸钠治疗组RA患者CD4+T细胞中IL-21(5.73%±1.59% vs. 4.75%±1.71%,P<0.05)表达上调:结论:RA 患者血清乳酸水平升高,可促进 CD4+T 细胞的活化和 IL-21 的分泌,并上调 RA 患者 Th17 和 Tph 细胞的比例。