Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production
Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production
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DOI：
10.1136/ard.2006.060772
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发表时间：
2007-05-01
影响因子：
27.4
通讯作者：
Mariette, Xavier
中科院分区：
文献类型：
--
作者：
Lavie, Frederic;Miceli-Richard, Corinne;Mariette, Xavier
背景：TNF家族的细胞因子B细胞活化因子（BAFF）参与自身免疫性疾病的发病。目的：了解利妥昔单抗治疗后BAFF血清蛋白和mRNA水平的变化。方法：对5例患者（2例狼疮患者，2例干燥综合征患者，1例类风湿关节炎患者）进行首次利妥昔单抗输注前和输注后12周（范围7 ~ 17周）的血清和外周血单个核细胞（PBMCs）分离。选取健康对照的单核细胞和B细胞共培养72 h，分别用ELISA和real-time PCR检测BAFF蛋白和mRNA水平。结果：利妥昔单抗治疗后，PBMCs血清中位BAFF蛋白水平和BAFF与肌动蛋白mRNA比值显著升高。在与自体B细胞共培养的单核细胞中，BAFF蛋白水平下降，mRNA水平稳定。在一名密切监测的患者中，PBMCs中BAFF与肌动蛋白mRNA比值的升高晚于BAFF血清水平。结论：B细胞耗竭后BAFF水平升高可能涉及两种不同的机制：(1)其受体的减少导致BAFF的释放；(2) BAFF mRNA转录的延迟调控。这可能有利于自身反应性B细胞的重新出现。
Background: The cytokine B cell-activating factor of the TNF family ( BAFF) is involved in the pathogenesis of autoimmune diseases.Objective: To access changes in serum protein and mRNA levels of BAFF after rituximab treatment.Methods: Serum and peripheral blood mononuclear cells (PBMCs) were isolated from five patients ( two with lupus, two with Sjogren's syndrome, one with rheumatoid arthritis) before and 12 weeks ( range 7-17) after a first course of rituximab infusion. Monocytes and B cells were selected from healthy controls and cocultured for 72 h. BAFF protein and mRNA levels were assessed by ELISA and real-time PCR, respectively.Results: After rituximab treatment, median serum BAFF protein level and BAFF to actin mRNA ratio in PBMCs significantly increased. In monocytes cocultured with autologous B cells, BAFF protein level decreased, whereas the mRNA level was stable. In one closely monitored patient, the mRNA ratio of BAFF to actin in PBMCs increased later than the BAFF serum level.Conclusions: Two distinct mechanisms are probably involved in the increase in BAFF level after B cell depletion: ( 1) the decrease in its receptors leading to a release of BAFF; ( 2) a delayed regulation of BAFF mRNA transcription. This could favour the re-emergence of autoreactive B cells.