Szalay Balázs, Vásárhelyi Barna, Cseh Aron, Tulassay Tivadar, Deák Magdolna, Kovács László, Balog Attila
Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, 14th floor, 1089, Budapest, Hungary,
Clin Rheumatol. 2014 Feb;33(2):175-85. doi: 10.1007/s10067-013-2352-x. Epub 2013 Aug 11.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by abnormal prevalence of Th1, Th2, Th17, and regulatory (Treg) subsets. Some data suggest that these subsets are influenced by anti-RA agents. Follow-up studies monitoring T cell phenotype in response to therapy are limited. We investigated the alteration of CD4+ T cell subset distribution after the initiation of disease-modifying antirheumatic drug (DMARD) (with glucocorticosteroid (GCS) and methotrexate (MTX)) and anti-TNFα therapy. We enrolled 19 treatment naive (early) RA patients and initiated GCS (in a dose of 16 mg/day for 4 weeks; then 8 mg/day). MTX, 10 mg/week, was started at week 4. We also enrolled 32 RA patients unresponsive to DMARD and initiated anti-TNFα therapy: adalimumab (ADA), 40 mg/2 weeks, n = 12; etanercept (ETA), 50 mg/weeks, n = 12; or infliximab (IFX) on week 0, 2, and 6, 3 mg/kg bw, n = 8. Blood was taken before and 4 and 8 weeks after the initiation of therapy. Ten volunteers served as controls. The T cell phenotype was assessed with flow cytometry. In early RA, Th1, Th2, and Th17 prevalence was higher, while Treg prevalence was lower than normal. GCS alone decreased Th2 prevalence. GCS + MTX decreased Th17 prevalence. Immune phenotype in unresponsive RA before anti-TNF therapy was as in early RA. Four and 8 weeks after initiating anti-TNF therapy, Th1 prevalence was higher than baseline in ETA or IFX, while it was stable in ADA groups. Th2 prevalence was higher than normal in ADA or IFX, while normalized in ETA group. In each group, Treg prevalence increased, while Th17 prevalence was at the baseline. The proinflammatory immune phenotype is normalized only under GCS + MTX combination in early RA. Anti-TNFα therapy exhibit marked effects on all the cell populations investigated (except Th17); some slight differences in this action exist between ADA, ETA, and IFX therapy.
类风湿关节炎（RA）是一种自身免疫性疾病，其特征在于Th1、Th2、Th17和调节性（Treg）亚群的异常流行。一些数据表明，这些亚群受抗RA药物影响。监测T细胞表型对治疗反应的随访研究有限。我们研究了疾病改善抗风湿药物（DMARD）（联合糖皮质激素（GCS）和甲氨蝶呤（MTX））及抗TNFα治疗开始后CD4 + T细胞亚群分布的变化。我们纳入了19例初治（早期）RA患者，并开始使用GCS（剂量为16 mg/天，持续4周；然后为8 mg/天）。MTX，10 mg/周，在第4周开始使用。我们还纳入了32例对DMARD无反应的RA患者，并开始抗TNFα治疗：阿达木单抗（ADA），40 mg/每2周，n = 12；依那西普（ETA），50 mg/周，n = 12；或英夫利昔单抗（IFX）在第0、2和6周使用，3 mg/kg体重，n = 8。在治疗开始前以及治疗开始后4周和8周采集血液。10名志愿者作为对照。用流式细胞术评估T细胞表型。在早期RA中，Th1、Th2和Th17的流行率较高，而Treg的流行率低于正常水平。单独使用GCS可降低Th2的流行率。GCS + MTX可降低Th17的流行率。抗TNF治疗前无反应RA的免疫表型与早期RA相同。开始抗TNF治疗后4周和8周，ETA或IFX组中Th1的流行率高于基线水平，而ADA组中则保持稳定。ADA或IFX组中Th2的流行率高于正常水平，而ETA组中则恢复正常。在每组中，Treg的流行率增加，而Th17的流行率维持在基线水平。仅在早期RA中GCS + MTX联合治疗下促炎免疫表型才恢复正常。抗TNFα治疗对所有研究的细胞群体（除Th17外）均有显著影响；ADA、ETA和IFX治疗在这一作用上存在一些细微差异。
