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用于预测利妥昔单抗临床反应的B淋巴细胞分型

B lymphocyte-typing for prediction of clinical response to rituximab.

作者信息

Brezinschek Hans-Peter, Rainer Franz, Brickmann Kerstin, Graninger Winfried B

出版信息

Arthritis Res Ther. 2012 Jul 6;14(4):R161. doi: 10.1186/ar3901.

DOI:10.1186/ar3901
PMID:22770118
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3580553/
Abstract

INTRODUCTION

The prediction of therapeutic response to rituximab in rheumatoid arthritis is desirable. We evaluated whether analysis of B lymphocyte subsets by flow cytometry would be useful to identify non-responders to rituximab ahead of time.

METHODS

Fifty-two patients with active rheumatoid arthritis despite therapy with TNF-inhibitors were included in the national rituximab registry. DAS28 was determined before and 24 weeks after rituximab application. B cell subsets were analyzed by high-sensitive flow cytometry before and 2 weeks after rituximab administration. Complete depletion of B cells was defined as CD19-values below 0.0001 x10⁹ cells/liter.

RESULTS

At 6 months 19 patients had a good (37%), 23 a moderate (44%) and 10 (19%) had no EULAR-response. The extent of B lymphocyte depletion in peripheral blood did not predict the success of rituximab therapy. Incomplete depletion was found at almost the same frequency in EULAR responders and non-responders. In comparison to healthy controls, non-responders had elevated baseline CD95⁺ pre-switch B cells, whereas responders had a lower frequency of plasmablasts.

CONCLUSIONS

The baseline enumeration of B lymphocyte subsets is still of limited clinical value for the prediction of response to anti-CD20 therapy. However, differences at the level of CD95⁺ pre switch B cells or plasmablasts were noticed with regard to treatment response. The criterion of complete depletion of peripheral B cells after rituximab administration did not predict the success of this therapy in rheumatoid arthritis.

摘要

引言

预测类风湿关节炎患者对利妥昔单抗的治疗反应很有必要。我们评估了通过流式细胞术分析B淋巴细胞亚群是否有助于提前识别对利妥昔单抗无反应者。

方法

52例尽管接受了肿瘤坏死因子抑制剂治疗但仍患有活动性类风湿关节炎的患者被纳入全国利妥昔单抗登记处。在应用利妥昔单抗前及应用后24周测定疾病活动评分28(DAS28)。在利妥昔单抗给药前及给药后2周通过高灵敏度流式细胞术分析B细胞亚群。B细胞完全耗竭定义为CD19值低于0.0001×10⁹细胞/升。

结果

6个月时,19例患者反应良好(37%),23例反应中等(44%),10例(19%)无欧洲抗风湿病联盟(EULAR)反应。外周血中B淋巴细胞的耗竭程度不能预测利妥昔单抗治疗的成功与否。EULAR反应者和无反应者中不完全耗竭的发生率几乎相同。与健康对照相比,无反应者基线时CD95⁺转换前B细胞升高,而反应者浆母细胞频率较低。

结论

B淋巴细胞亚群的基线计数对预测抗CD20治疗反应的临床价值仍然有限。然而,在治疗反应方面,注意到CD95⁺转换前B细胞或浆母细胞水平存在差异。利妥昔单抗给药后外周B细胞完全耗竭的标准不能预测类风湿关节炎患者该治疗的成功与否。

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