目的:CD4+CXCR5+PD-1hi滤泡辅助性T(Tfh)细胞驻留在淋巴器官的生发中心(GC),参与类风湿关节炎(RA)的发病机制;它们的循环对应物(cTfh-frequency)在RA中增加,并与GCTfh细胞池相关。我们的目的是研究abatacept(ABT)或TNF阻滞剂(TNFb)对RA中cTfh频率的影响。
方法:从长期接受csDMARDS的血清呈阳性的RA患者(n=45)中抽取外周血,TNFb(n=59),或ABT(n=34),和健康对照(HC)(n=137)。此外,对开始TNFb(n=19)或ABT(n=22)的csDMARDS(n=41)反应不完全的患者,在0和12个月进行了研究。通过细胞计数检查cTfh-频率。
结果:与HC相比,在长期接受csDMARDs或TNFb但不接受ABT的长期血清阳性RA中,cTfh频率增加。从csDMARD升级后,cTfh频率在接受TNFb治疗的患者中没有变化,但在接受ABT治疗的患者中降至HC水平.在ABT组中,获得12M缓解(12Mr)的患者的基线cTfh频率更高,与那些保持活跃的人(12Ma):缓解>0.38%(感觉。92%,Sp.90%),或25.3.相反,在TNFB组中,12Mr与12Ma的基线cTfh频率较低:未缓解的0m截止值>0.44%(Senss。67%,Sp.90%),OR8.5.
结论:ABT而不是TNFb,能够减少RA中的cTfh频率。较高的基线cTfh频率预测对ABT的良好响应,但对TNFb的响应较差。
OBJECTIVE: CD4+CXCR5+PD-1hi follicular helper T (Tfh) cells dwell in the germinal centers (GCs) of lymphoid organs and participate in Rheumatoid Arthritis (RA) pathogenesis; the frequency of their circulating counterparts (cTfh-frequency) is expanded in RA and correlates with the pool of GC Tfh cells. Our objective was to study the effect of abatacept (ABT) or TNF blockers (TNFb) on the cTfh-frequency in RA.
METHODS: Peripheral blood was drawn from seropositive-longstanding RA patients chronically receiving csDMARDS (n = 45), TNFb (n = 59), or ABT (n = 34), and healthy controls (HC) (n = 137). Also, patients with an incomplete response to csDMARDS (n = 41) who initiated TNFb (n = 19) or ABT (n = 22), were studied at 0 and 12 months. The cTfh-frequency was examined by cytometry.
RESULTS: As compared with HC, an increased cTfh-frequency was seen in seropositive-longstanding RA chronically receiving csDMARDs or TNFb but not ABT. After escalating from csDMARDs, the cTfh-frequency did not vary in patients who were given TNFb but decreased to HC levels in those given ABT. In the ABT group, the baseline cTfh-frequency was higher for patients who attained 12M remission (12Mr), vs those who remained active (12Ma): 0m cutoff for remission >0.38% (Sens. 92%, Sp. 90%), OR 25.3. Conversely, in the TNFb group, the baseline cTfh-frequency was lower for 12Mr vs 12Ma: 0m cutoff for non-remission >0.44% (Sens. 67%, Sp. 90%), OR 8.5.
CONCLUSIONS: ABT but not TNFb, is able to curtail the cTfh-frequency in RA. A higher baseline cTfh-frequency predicts a good response to ABT but a poor response to TNFb.