摘要
目的观察类风湿关节炎（RA）患者外周血中滤泡辅助性T细胞（Tfh）及T辅助细胞9（Th9）的变化，并与病情活动性及脏器受累等临床资料进行相关性分析，探讨Tfh及Th9在RA发病过程中可能的免疫学发病机制。方法选择36例RA患者和22例健康对照。根据病情活动度不同将病例组分为病情高度活动组（22例）、病情中度活动组（14例），流式细胞仪检测RA和正常对照组外周血单个核细胞（PBMCs）中CD4-FITC、CXCR5-PE、ICOS-APC标记的CD4＋CXCR5＋ICOS＋（Tfh）及，CD8-FITC、CD3．APC、IL9-PE标记的CD3＋CD8-IL-9＋（Th9）比例。分析Tfh及Th9与RA患者的血沉（ESR）、C反应蛋白（CRP）、类风湿因子（RF）、关节压痛数、肿胀数及骨质破坏等指标的相关性；分析Tfh与Th9的关系。结果RA患者的Tfh表达率明显高于对照组（Z=-6．082，P=0．000），RA患者Th9的表达率亦高于对照组（0．989±0．498VS0．213±0．084，t=13．063，P=0．000）；RA重度活动组Tfh表达率亦高于中度活动患者的表达率（3．880±1．255V82．678±1．022，t=2．990，P=0．005），且两组Tfh的表达率均高于对照组（P均〈0．01）；RA重度活动患者Th9表达率高于中度患者（1．181±0．523VS0．686±0．254，t=4．043，P=0．000），且两组Th9的表达率亦均高于对照组（P均〈0．01）；Tfh细胞数与RA患者DAS28（r=0．571，P=0．000）、ESR（r=0．375，P=0．029）、CRP（r=0．357，尸=0．032）、关节压痛数（r=0．598，P=0．000）、RF（r=0．421，P=0．023）及抗CCP滴度（r=0．421，P=0．023）正相关；与病程、晨僵、关节肿胀数、骨质破坏、心电图异常无相关性。Th9表达的百分率与RA患者的DAS28（r=0．461，P=0．005）、ESR（r=0．347，P=0．042）、CRP（r=0．384，P=0210）、关节压痛数（r=0．341，P=0．042）、关节肿胀数（r=0．347，P=0．038）及RF（r=0．379，．P=0．025）正相关，与病程、晨僵时间、抗CCP滴度、心电图异常及骨质破坏无相关性；Tfh与Th9在外周血中的表达率呈正相关（r=0．727，P=O．000）。结论RA患者外周血Tih及Th9的比例显著升高，且与疾病活动度及相关炎症指标明显相关，提示Tfh及Th9可能参与RA的发病及病情发展。
Objective To investgate the expression of Tfh and Th9 in the peripheral blood of rheu- matoid arthritis（ RA）, and to analyze the relationship between those cells and disease activity, organs of in- volvement, eet. , and to underly the possible immunological meehananism of RA. Methods Peripheral blood Tfh cells and Th9 cells, define as the CD4＋ CXCR5＋ ICOS＋ and CD3＋ CD8＋ IL-9＋ population, were ex- amined by flow cytometry in 36 patients with RA and 22 case of age- and gender- matched health controls. According to 28-joint Disease Activity Score （DAS28）, patients were divied into two groups： high disease activity（ n = 22） , moderate disease activity（ n= 14 ）. And then to analyzed the correlation among the Tfh, Th9 and clinical data of RA , such as ESR, CRP, RF, the number of tender joints,the number of swollen joints and bone destruction, etc.. While to analyzed the correlation between Th9 and Tfh. Results The ex- pression of Tfh （Z=-6. 082,P=0.000） and Th9（0. 989±0.498 vs 0. 213±0. 084, t= 13. 063 ,P=0. 000） in PBMCs of RA was significantly higher than normal controls. Meanwhile, the expression of Tfh （3. 880±1. 255 vs 2. 678±1. 022, t = 2. 990, P = 0. 005 ） and Th9 （ 1. 181±0. 523 vs 0. 686±0. 254, t = 4. 043, P = 0. 000） in high activity of group were higher than those moderate. The percentage of Tfh and Th9 in the twogroups were all significantly higher than controls（P〈0. 01 ）. There was a positive correlation with Tfh and DAS28 （ r = 0.571, P = 0. 000）, ESR （ r = 0. 375, P = 0. 029）, CRP （ r = 0. 357, P = 0.032 ）, the number of tender joints（r = 0. 598, P= 0, 000）, RF （ r=0. 421, P = 0. 023 ） and anti-CCP （ r = 0. 421, P = 0. 023 ）. There were no relationship with Tfh and course, morning stiffness, the number of swollen joints, bone erosion and the abnormal of EKG. There was a positive correlation with Th9 and DAS28 （r = 0. 461, P= 0. 005 ）, ESR（r=0.347, P=0. 042）, CRP（r=0. 384, P=0. 210）, the number of tender joints（r=O. 341, P= 0. 042 ）, the number of swollen joints （ r = 0. 347, P = 0. 038 ） and RF （ r = 0. 379, P = 0.025 ） respectively. There were no relationship with Th9 and course, morning stiffness, CCP, the abnormal of EKG, bone ero- sion. There was a positive correlation with Tfh and Th9 （r = 0. 727, P = 0.000）. Conclusion The expres- sion of Tfh and Th9 were increase significantly, which those cells were close relationship with the disease ac- tivity and some data. These results indicate that the abnormality of Tfh and Th9 may play an important role in the pathogenesis of RA.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2012年第2期114-118,共5页
Chinese Journal of Microbiology and Immunology
