Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy

Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy
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DOI:
10.1093/rheumatology/kel148
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发表时间:
2007-01-01
期刊:
影响因子:
5.5
通讯作者:
Edwards, J. C. W.
Edwards, J. C. W.
中科院分区:
医学1区
文献类型:
--
作者:
Leandro, M. J.;Cooper, N.;Edwards, J. C. W.

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Objective.评估利妥昔单抗治疗后类风湿关节炎(RA)患者骨髓(BM)中B系细胞的存在和表型。研究了6名患者。治疗后3个月收集骨髓穿刺液,采用四色流式细胞术进行分析。骨髓样本中的CD 19+(B系)细胞在淋巴门中的变化范围为0.1%至3.25%。CD 34+细胞从1.23%变化到4.86%。CD 34+细胞定向为B系的比例在0和42.19%之间变化。在1例病例中未检测到前B细胞。在患者5和6中,大多数B细胞前体是前B细胞(分别占CD 19+细胞的50%和62%),在患者3和4中是前B细胞(64%和70%),在患者1中是未成熟B细胞(44%)。CD 19+细胞上可检测到的CD 20表达较低或不存在。浆细胞占总有核细胞的0.01 ~ 0.36%。有证据表明BM更完全耗竭的患者的临床应答持续时间更长。在这个用利妥昔单抗治疗的RA患者的小队列中,检测到CD 19 + BM细胞的比例和表型的差异。这些差异表明所达到的消耗程度的变化,并与复发时间相关。虽然pro-B-细胞不被利妥昔单抗直接靶向,因为它们不表达CD 20,但水平出乎意料地低。
Objective. To assess the presence and phenotype of B-lineage cells in the bone marrow (BM) of rheumatoid arthritis (RA) patients after rituximab therapy.Methods. Six patients were studied. BM aspirates were collected 3 months after the treatment and analysed using the four-colour flow cytometry.Results. CD19+ (B-lineage) cells in BM samples varied from 0.1 to 3.25% in the lymphoid gate. CD34+ cells varied from 1.23 to 4.86%. The proportion of CD34+ cells committed to the B-lineage varied between 0 and 42.19%. Pro-B-cells were undetectable in one case. The majority of B-cell precursors were pro-B-cells in Patients 5 and 6 (50 and 62% of CD19+ cells, respectively), pre-B-cells in Patients 3 and 4 (64 and 70%) and immature B-cells in Patient 1 (44%). Detectable CD20 expression on CD19+ cells was either low or absent. Plasma cells varied from 0.01 to 0.36% of the total nucleated cells. There was a trend towards longer duration of clinical response in patients with evidence of more complete depletion in BM.Conclusion. In this small cohort of RA patients treated with rituximab, differences in proportion and phenotype of CD19+ BM cells were detected. These differences suggest variation in the degree of depletion achieved and correlate with time to relapse. Although pro-B-cells are not targeted directly by rituximab as they do not express CD20, the levels were unexpectedly low.