Recovery of B-cell homeostasis after rituximab in chronic graft-versus-host disease
Recovery of B-cell homeostasis after rituximab in chronic graft-versus-host disease
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DOI：
10.1182/blood-2010-10-307819
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发表时间：
2011-02-17
期刊：
影响因子：
20.3
通讯作者：
Ritz, Jerome
中科院分区：
文献类型：
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作者：
Sarantopoulos, Stefanie;Stevenson, Kristen E.;Ritz, Jerome
研究利妥昔单抗（抗cd20）对肿瘤坏死因子家族B细胞活化因子（BAFF）和B细胞的影响，可以更好地确定B细胞稳态在慢性移植物抗宿主病（cGVHD）病理生理中的意义。我们研究了20例cGVHD患者，中位时间为利妥昔单抗治疗后25个月，大多数患者的b细胞总数恢复。总共55%的患者有稳定/改善的cGVHD，与利妥昔单抗无反应的患者相比，这些患者的总b细胞数量明显更高。尽管在使用利妥昔单抗之前，cGVHD组之间的总b细胞数量没有显著差异，但在后来稳定/改善的cGVHD患者中，b细胞前体数量呈比例增加。使用利妥昔单抗后，所有患者的BAFF水平均升高。与稳定/改善组的b细胞恢复一致，BAFF/ b细胞比率和CD27(+) b细胞频率显著下降。稳定/改善型cGVHD患者的外周B细胞池主要由初始IgD(+) B细胞组成。相比之下，利妥昔单抗无应答的cGVHD患者BAFF持续升高，循环B细胞具有活化的BAFF- r (Lo)CD20（Lo）细胞表面表型的优势。因此，初始b细胞重构和BAFF/ b细胞比例降低与利妥昔单抗治疗cGVHD后的临床反应有关。我们的发现开始描绘b细胞稳态机制对人类免疫耐受的重要作用。(血。2011;117 (7):2275 - 2283)
Investigation of the effects of rituximab (anti-CD20) on B-cell-activating factor of the tumor necrosis factor family (BAFF) and B cells would better define the significance of B-cell homeostasis in chronic graft-versus-host disease (cGVHD) pathophysiology. We studied 20 cGVHD patients at a median of 25 months after rituximab treatment when most patients had recovered total B-cell numbers. A total of 55% of patients had stable/improved cGVHD, and total B-cell numbers in these patients were significantly higher compared with rituximab-unresponsive patients. Although total B-cell number did not differ significantly between cGVHD groups before rituximab, there was a proportional increase in B-cell precursors in patients who later had stable/improved cGVHD. After rituximab, BAFF levels increased in all patients. Coincident with B-cell recovery in the stable/ improved group, BAFF/B-cell ratios and CD27(+) B-cell frequencies decreased significantly. The peripheral B-cell pool in stable/improved cGVHD patients was largely composed of naive IgD(+) B cells. By contrast, rituximab-unresponsive cGVHD patients had persistent elevation of BAFF and a predominance of circulating B cells possessing an activated BAFF-R(Lo)CD20(Lo) cell surface phenotype. Thus, naive B-cell reconstitution and decreased BAFF/B-cell ratios were associated with clinical response after rituximab in cGVHD. Our findings begin to delineate B-cell homeostatic mechanisms important for human immune tolerance. (Blood. 2011;117(7):2275-2283)