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首页> 外文期刊>European journal of dermatology: EJD >Profiling lymphocyte subpopulations in peripheral blood under efalizumab treatment of psoriasis by multi epitope ligand cartography (MELC) robot microscopy.
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Profiling lymphocyte subpopulations in peripheral blood under efalizumab treatment of psoriasis by multi epitope ligand cartography (MELC) robot microscopy.

机译:依法利珠单抗治疗牛皮癣的外周血中淋巴细胞亚群的分析由多表位配体制图(MELC)机器人显微镜进行。

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摘要

CD11a-blocking efalizumab has recently been approved as a systemic treatment of moderate to severe chronic plaque psoriasis. When treating 6 psoriasis patients with efalizumab over 12 weeks in the present study, we observed an overall good tolerability and 5 treatment responders characterized by a decrease of PASI from 21.3 +/- 5.4 to 3.9 +/- 0.6. The accompanying significant increase of peripheral blood lymphocytes from 1.9 +/- 0.7 to 4.3 +/- 1.0 x 10(9)/L (p < 0.05) was analyzed by multi epitope ligand cartography (MELC) robot microscopy. Thereby a high-dimension simultaneous multiplex immunophenotyping was pursued using 39 fluorophore-labeled antibodies including labeled efalizumab and 3 other affinity reagents such as lectins. Due to efalizumab treatment there was a substantial decrease of the cellular expression of CD11a (detected by mab clone 25.3.1) and efalizumab binding sites (EfaBSs). This was paralleled by an increase of the number of EfaBS- and EfaBS+ lymphocytes by a factor of 2.4x and 2.2x, respectively. The latter effect was mainly derived from a subpopulation showing a low degree of EfaBS expression. Efalizumab treatment led furthermore to an increase of the numbers of CD3+, CD4+, CD8+, CD44+, CD45+, CD45R0+, CD45 RA+, CD52+, CD58+, CD247+, HLA-DR+ and Sambucus nigra lectin-reactive lymphocytes (by factors from 2.0 to 3.3x). In terms of a combinatorial molecular phenotype we identified a CD3+/CD4+/CD44+/CD52+ lymphocyte subpopulation which accumulated most predominantly from 0.824 +/- 0.270 x 10(9)/L up to 1.616 +/- 0.152 x 10(9)/L under efalizumab treatment (p < 0.01). Thus, the current study extends the knowledge of efalizumab-dependent perturbations of recirculating blood lymphocyte subpopulations in psoriasis patients.
机译:最近,已批准阻断CD11a的依法珠单抗作为中度至重度慢性斑块状牛皮癣的全身治疗药物。在本研究中,当在12周内治疗6例使用efalizumab的牛皮癣患者时,我们观察到总体耐受性良好,并且5个治疗反应者的特征是PASI从21.3 +/- 5.4降低至3.9 +/- 0.6。通过多表位配体制图(MELC)机器人显微镜分析了伴随的外周血淋巴细胞从1.9 +/- 0.7显着增加到4.3 +/- 1.0 x 10(9)/ L(p <0.05)。因此,使用39种荧光团标记的抗体(包括标记的efalizumab和3种其他亲和试剂,如凝集素)进行了高维同时多重免疫表型分析。由于使用了efalizumab治疗,CD11a(通过mab克隆25.3.1检测到)和efalizumab结合位点(EfaBSs)的细胞表达大大降低。与此同时,EfaBS-和EfaBS +淋巴细胞的数量分别增加了2.4倍和2.2倍。后者的作用主要来自显示低EfaBS表达程度的亚群。依法利珠单抗治疗进一步导致CD3 +,CD4 +,CD8 +,CD44 +,CD45 +,CD45R0 +,CD45 RA +,CD52 +,CD58 +,CD247 +,HLA-DR +和黑棕蛇凝集素反应性淋巴细胞数量增加(从2.0到3.3倍) )。就组合分子表型而言,我们鉴定出CD3 + / CD4 + / CD44 + / CD52 +淋巴细胞亚群,其积累最主要是从0.824 +/- 0.270 x 10(9)/ L到1.616 +/- 0.152 x 10(9)/ L在efalizumab治疗下(p <0.01)。因此,本研究扩展了牛皮癣患者的依法珠单抗依赖性循环血淋巴细胞亚群扰动的知识。

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