摘要
目的检测类风湿关节炎(rheumatoid arthritis,RA)并发骨质疏松(osteoporosis,OP)患者外周血淋巴细胞亚群的表达水平并探讨其临床意义.方法收集山西医科大学第二医院住院诊治的734例RA患者的基本临床资料、外周血淋巴细胞亚群及骨密度(bone mineral density,BMD)检查结果,根据BMD结果以及是否曾有脆性骨折史将以上患者分为RA未并发OP组551例和并发OP组183例,比较两组临床资料的不同,同时选取81例健康人群作为健康对照组,分析3组外周血淋巴细胞亚群的差异,并对RA并发OP患者行BMD与外周血淋巴细胞亚群间的相关性分析.结果RA患者OP发生率为24.93%,其中12.57%有骨折史.RA并发OP组女性患者比例明显高于未并发OP组(P=0.021),且年龄较大(61.85±10.36 vs.56.63±12.01,P<0.001),病程更长(7.17±5.82 vs.5.28±6.33,P=0.001),疾病活动相关指标更高(P<0.05).相较于健康对照组,RA未并发OP组B细胞水平下降,Th17细胞水平升高,但差异均无统计学意义,Th2细胞及Th17/Treg比值明显升高(P<0.01),Treg细胞及Th1/Th2比值降低(P<0.05);RA并发OP组B细胞绝对计数下降(P<0.05),Th17细胞水平及Th17/Treg比值明显升高(P<0.01),Treg细胞水平显著下降(P<0.001).相较于RA未并发OP组,并发OP组B细胞及Treg细胞水平均明显下降(P<0.01),Th17细胞水平及Th17/Treg比值升高(P<0.05).RA并发OP患者的腰椎BMD与B淋巴细胞和Treg细胞绝对计数及百分计数呈正相关(B淋巴细胞r=0.290、0.315;Treg细胞r=0.318、0.248,P<0.05),与Th17细胞绝对计数和百分计数及Th17/Treg比值呈负相关(Th17细胞r=-0.254、-0.265;Th17/Treg r=-0.242,P<0.05);同样股骨BMD与B淋巴细胞和Treg细胞绝对计数及百分计数也呈正相关(B淋巴细胞r=0.238、0.256;Treg细胞r=0.259、0.255,P<0.05),与Th17细胞绝对计数和百分计数及Th17/Treg比值也呈负相关(Th17细胞r=-0.248、-0.283;Th17/Treg r=-0.216,P<0.05).结论RA并发OP患者存在B细胞显著下降和Th17/Treg比例失衡,此与RA患者本身的免疫紊乱密切相关,在RA疾病早期关注免疫微环境并调节其平衡对预防骨质疏松的发生至关重要.
Objective To investigate the expression of peripheral blood lymphocyte subsets in rheumatoid ar-thritis patients with osteoporosis and explore its clinical significance.Methods A total of 734 patients with RA and 81 healthy controls(HC)were enrolled in this study.All peripheral lymphocyte subsets of these participants were assessed by flow cytometry.Patients were divided into RA-non-OP group and RA-OP group according to their BMD of lumbar or bilat-eral hip and the history of fragility fracture for further comparation of the general clinical data.The difference of peripheral blood lymphocyte subsets among HC,RA-non-OP group,and RA-OP group were analyzed as well as the correlation be-tween BMD and the lymphocyte subsets in RA-OP patients.Results Among 183(24.93%)RA patients complicated with OP,there were more female(P=0.021).Compared with RA-non-OP patients,not only an older age(61.85±10.36 vs.56.63±12.01,P<0.001)and a longer disease duration(7.17±5.82 vs.5.28±6.33,P=0.001)but also a higher disease activity(P<0.05)were observed in RA-OP patients.Compared with HC,the level of B cells in RA-non-OP group was decreased,whereas Th17 increased.There were increase in Th2 cells and the ratio of Th17/Treg(P<0.01).Treg cells and Th1/Th2 ratio were lower(P<0.05).The decrease of B cells was more obvious in patients with OP(P<0.05).There were also increase in Th17 cells and the ratio of Th17/Treg(P<0.01).However,Treg cells decreased distinctly(P<0.001).Compared with RA-non-OP group,the level of B and Treg cells in RA-OP group were lower(P<0.01).There were significant increase in Th17 cells and the ratio of Th17/Treg(P<0.05).The BMD of lumbar spine in RA-OP patients was positively correlated with the level of B(r=0.290,0.315,P<0.05)and Treg cells(r=0.318,0.248,P<0.05),and negatively with Th17 cells(r=-0.254,-0.265,P<0.05)and Th17/Treg ratio(r=-0.242,P<0.05).Similarly,the BMD of the either hip in RA-OP patients was positively correlated with the level of B(r=0.238,0.256,P<0.05)and Treg cells(r=0.259,0.255,P<0.05),and negatively with Th17 cells(r=-0.248,-0.283,P<0.05)and Th17/Treg ratio(r=-0.216,P<0.05).Conclusions The further decline of B cells and the immune disor-der caused by Th17/Treg imbalance may also contribute to OP in RA patients.It is important to pay attention to the immune mi-croenvironment and immune regulation should be considered at the early stage of RA to prevent the occurrence of OP.
作者
程婷
张升校
牛红青
王佳
刘晓庆
严明
来娜琳
毛小娟
程斌
李小峰
CHENG Ting;ZHANG Sheng-xiao;NIU Hong-qing;WANG Jia;LIU Xiao-qin;YAN Min;LAI Na-lin;MAO Xiao-juan;CHENG Bin;LI Xiao-feng(Department of Rheumatology,The Second Hospital of Shanxi Medical University,Taiyuan 030001,China;Transportation and Logistics,Taiyuan University of Science and Techonology,Taiyuan 030024,China)
出处
《中华骨质疏松和骨矿盐疾病杂志》
CSCD
北大核心
2020年第1期8-14,共7页
Chinese Journal Of Osteoporosis And Bone Mineral Research
基金
国家自然科学基金(81871295)。