[难治性原发性免疫性血小板减少症患者对利妥昔单抗无反应]

[Absence of response to rituximab in patients with refractory primary immune thrombocytopenia].

作者信息

Ma Hongyan, Wang Yihao, Sun Ling, Gong Hongtao

机构信息

Department of Hematology, Second Affiliated Hospital, Zhengzhou University, Zhengzhou 450014, China. Email:

出版信息

Zhonghua Yi Xue Za Zhi. 2014 Oct 21;94(38):3011-3.

PMID:25547706

Abstract

OBJECTIVE

To explore the possible causes for an absence of response to rituximab (RTX) in patients with refractory immune thrombocytopenia (ITP).

METHODS

A total of 20 refractory ITP patients on RTX therapy and 10 health volunteers were recruited from 2008 to 2013. Memory T lymphocytes (Tm) (CD4(+)CD45RO(+)) and B lymphocytes (CD19(+)CD20(+)) in peripheral blood (PB) were examined by flow cytometry (FCM). And enzyme-linked immunosorbent assay (ELISA) was employed for detecting the platelet-associated antibodies IgG/IgM (PAIgG/IgM).

RESULTS

(1) 12 patients with refractory ITP achieved a good response after therapy with RTX (effective RTX group) and 8 cases failed to respond (ineffective RTX group). The PB levels of CD4(+)CD45RO(+)Tm were 41.33% ± 9.62% and 45.36% ± 8.57% respectively at pre-therapy and post-therapy in ineffective RTX group. And significant differences existed between ineffective and effective RTX groups (22.36% ± 11.57%, 26.65% ± 6.32%) versus health volunteers (19.72% ± 7.35%, 20.64% ± 7.35%) (all P < 0.05) . No statistical differences existed in the PB level of CD4(+)CD45RO(+)Tm between pre-therapy and post-therapy in ineffective or effective RTX group (both P > 0.05); (2) The PB level of CD19(+)CD20(+)B lymphocytes in RTX ineffective group was lower than that at pre-therapy in RTX effective group (16.36% (6.17%-27.53%) vs 45.72% (35.80%-57.19%), P < 0.05) . No significant difference existed in the level of CD19(+)CD20(+)B at post-therapy between ineffective and effective RTX groups (6.67% (4.09%-19.17%) vs 5.19% (3.78%-17.39%), P > 0.05). And significant differences existed in the PB level of CD19(+)CD20(+)B between pre-therapy and post-therapy in ineffective or effective RTX group (both P > 0.05); (3) PAIgG/IgM was not detected in RTX ineffective group. And PAIgG/IgM was found in 11 cases at pre-therapy versus 1 case at post-therapy in RTX effective group.

CONCLUSION

CD4(+)CD45RO(+)Tm is probably associated with an absence of response to RTX in patients with refractory ITP.

摘要

目的

探讨难治性免疫性血小板减少症（ITP）患者对利妥昔单抗（RTX）无反应的可能原因。

方法

2008年至2013年共招募了20例接受RTX治疗的难治性ITP患者和10名健康志愿者。采用流式细胞术（FCM）检测外周血（PB）中的记忆T淋巴细胞（Tm）（CD4(+)CD45RO(+)）和B淋巴细胞（CD19(+)CD20(+)）。采用酶联免疫吸附测定（ELISA）检测血小板相关抗体IgG/IgM（PAIgG/IgM）。

结果

（1）12例难治性ITP患者经RTX治疗后获得良好反应（RTX有效组），8例无反应（RTX无效组）。RTX无效组治疗前和治疗后PB中CD4(+)CD45RO(+)Tm水平分别为41.33%±9.62%和45.36%±8.57%。RTX无效组与有效组（22.36%±11.57%，26.65%±6.32%）与健康志愿者（19.72%±7.35%，20.64%±7.35%）之间存在显著差异（均P<0.05）。RTX无效组或有效组治疗前和治疗后PB中CD4(+)CD45RO(+)Tm水平无统计学差异（均P>0.05）；（2）RTX无效组PB中CD19(+)CD20(+)B淋巴细胞水平低于RTX有效组治疗前（16.36%（6.17%-27.53%）对45.72%（35.80%-57.19%），P<0.05）。RTX无效组和有效组治疗后CD19(+)CD20(+)B水平无显著差异（6.67%（4.09%-19.17%）对5.19%（3. .78%- .39%），P>0.05）。RTX无效组或有效组治疗前和治疗后PB中CD19(+)CD20(+)B水平存在显著差异（均P>0.05）；（3）RTX无效组未检测到PAIgG/IgM。RTX有效组治疗前11例检测到PAIgG/IgM，治疗后1例检测到。