CAJ | 학술논문

目的观察弥漫大B细胞淋巴瘤(DLBCL)患者不同治疗阶段胸腺近期输出naive T 细胞的动态变化,评估其与疾病预后的关系以及化疗对免疫重建潜能的影响.方法利用实时定量PCR(TaqMan)方法分别检测30例DLBCL患者不同治疗阶段外周血单个核细胞(PBMNC)中T细胞受体重排删除DNA环(TREC)的水平(以每1000个PBMNC中的含量表示),并根据外周血中CD3细胞阳性率计算CD3+T细胞中TREC水平.以12名年龄相匹配的正常人作为对照.结果与正常人外周血中的TREC水平相比,不同基因亚型DLBCL患者外周血中的TREC水平均明显低下,生发中心B细胞样(GCB)型患者组的TREC水平高于非生发中心B细胞样(non-GCB)型患者组.化疗前GCB型患者组PBMNC和CD3+T细胞中的TREC水平分别为0.91±0.15和1.22±0.69,而non-GCB型患者组分别为0.43±0.29和0.64±0.44.治疗前的TREC水平与患者的国际预后指数(IPI)评分明显相关(r=-0.441,P=0.015).化疗后的TREC水平进一步降低,治疗6个周期后最低,GCB型患者组PBMNC和CD3+T细胞中的TREC水平分别为0.63±0.34和0.89±0.65,而non-GCB型患者组分别为0.19±0.11和0.27±0.25.大多数患者化疗结束后3个月TREC水平上升较为明显.5例患者化疗后6个月的TREC水平已接近正常.结论 DLBCL患者的胸腺近期输出功能严重受损,化疗前的胸腺近期输出功能与疾病的预后有重要关系,化疗影响患者的T细胞免疫功能重建潜能.
목적 관찰미만대B세포림파류(DLBCL)환자불동치료계단흉선근기수출naive T 세포적동태변화,평고기여질병예후적관계이급화료대면역중건잠능적영향.방법 이용실시정량PCR(TaqMan)방법분별검측30례DLBCL환자불동치료계단외주혈단개핵세포(PBMNC)중T세포수체중배산제DNA배(TREC)적수평(이매1000개PBMNC중적함량표시),병근거외주혈중CD3세포양성솔계산CD3+T세포중TREC수평.이12명년령상필배적정상인작위대조.결과 여정상인외주혈중적TREC수평상비,불동기인아형DLBCL환자외주혈중적TREC수평균명현저하,생발중심B세포양(GCB)형환자조적TREC수평고우비생발중심B세포양(non-GCB)형환자조.화료전GCB형환자조PBMNC화CD3+T세포중적TREC수평분별위0.91±0.15화1.22±0.69,이non-GCB형환자조분별위0.43±0.29화0.64±0.44.치료전적TREC수평여환자적국제예후지수(IPI)평분명현상관(r=-0.441,P=0.015).화료후적TREC수평진일보강저,치료6개주기후최저,GCB형환자조PBMNC화CD3+T세포중적TREC수평분별위0.63±0.34화0.89±0.65,이non-GCB형환자조분별위0.19±0.11화0.27±0.25.대다수환자화료결속후3개월TREC수평상승교위명현.5례환자화료후6개월적TREC수평이접근정상.결론 DLBCL환자적흉선근기수출공능엄중수손,화료전적흉선근기수출공능여질병적예후유중요관계,화료영향환자적T세포면역공능중건잠능.
Objective To detect the changes of naive T cell level of thymic recent output at different stages of treatment in patients with diffuse large B-cell lymphoma (DLBCL), thereby to evaluate the relationship of thymic recent output function with prognosis and the impact of chemotherapy on the potential of immunological recovery. Methods The levels of T-cell receptor rearrangement excision circles (TREC) in DNA of peripheral blood mononuclear cells (PBMNC) from 30 DLBCL patients were monitored before, during, until 3 months and 6 months after chemotherapy by real-time PCR (TaqMan), and TREC-level was detected according to the number of CD3 positive(CD3+) cells. Twelve normal individuals who matched in age were served as controls. Results There was a dramatic reduction of TREC values in all DLBCL patients among which TREC values in germinal center B-cell-like-DLBCL (GCB-DLBCL) were higher than those in non-GCB-DLBCL, as compared with TREC values of normal individual in peripheral blood. The mean values of TREC were 0.91±0.15/1000 PBMNCs and (1.22±0.69)/1000 CD3+ cells in GCB-DLBCL, (0.43±0.29)/1000 PBMNCs and (0.64±0.44)/1000 CD3+ cells in non-GCB-DLBCL before chemotherapy. TREC values were significantly associated with lower international prognostic index (IPI) grade (r=-0.441, P=0.015). TREC-level in DLBCL patients was further decreased after chemotherapy, and reached to the lowest level after the 6th cycle of chemotherapy, and during the corresponding period, the mean values of TREC were (0.63±0.34)/1000 PBMNCs and (0.89±0.65)/1000 CD3+cells in GCB-DLBCL, (0.19±0.11)/1000 PBMNCs and (0.27±0.25)/1000 CD3+ cells in non-GCB-DLBCL. TREC-level began to rise obviously 3 months after the last cycle of chemotherapy in most of the DLBCL patients, and came close to normal level in five cases of patients 6 months after the last cycle of chemotherapy. Conclusions Thymic recent output function was impaired severely in DLBCL patients. There was an important relationship between thymic recent output function before chemotherapy and prognosis, and chemotherapy had influenced the potential of immunological recovery.