Effect of long-term belimumab treatment on B cells in systemic lupus erythematosus: extension of a phase II, double-blind, placebo-controlled, dose-ranging study.
Effect of long-term belimumab treatment on B cells in systemic lupus erythematosus: extension of a phase II, double-blind, placebo-controlled, dose-ranging study.
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DOI：
10.1002/art.27189
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发表时间：
2010-01
影响因子：
--
通讯作者：
Davidson, Anne
中科院分区：
文献类型：
--
作者：
Jacobi, Annett M.;Huang, Weiqing;Wang, Tao;Freimuth, William;Sanz, Inaki;Furie, Richard;Mackay, Meggan;Aranow, Cynthia;Diamond, Betty;Davidson, Anne
目的：了解长期抑制BLyS对人类系统性红斑狼疮的影响。17名SLE患者参加了BLyS特异性抑制剂belimumab加标准护理治疗的临床试验。用流式细胞仪进行淋巴细胞表型分析。采用ELISpot法对循环抗体分泌细胞进行计数。用一种识别VH4-34基因产物的抗体对血清进行酶联免疫吸附试验。淋巴细胞计数、免疫球蛋白水平和抗dsDNA抗体水平是临床试验分析的一部分。分别在第0、84、168、365、532天和730天采集样本。从第84-168天开始，B细胞总数从基线开始下降。这是由于幼稚和过渡性B细胞减少所致。CD2 7+/IGD+记忆B细胞和浆母细胞仅在532天后减少，而CD2 7+/IGD−记忆B细胞不受影响，T细胞也没有变化。血清IgM水平在84~168日龄之间开始下降，但在研究期间，血清中的免疫球蛋白、免疫球蛋白抗体、抗DNA抗体或VH4-34抗体水平没有变化。在第0天，SLE患者比正常对照组有更多的免疫球蛋白M、免疫球蛋白G和自身抗体产生B细胞。与表型和血清学数据一致，在365天和532天，总的产生IgM的细胞的频率仅有轻微的下降，但没有产生IgG的细胞。我们的数据证实了新形成的B细胞依赖BLyS在人类中生存。相比之下，记忆B细胞和浆细胞对选择性BLyS抑制较不敏感。
To understand the effects of prolonged BLyS inhibition in human SLE. 17 SLE patients enrolled in a clinical trial of belimumab, a BLyS-specific inhibitor, plus standard of care therapy were studied. Phenotypic analysis of lymphocytes was performed using flow cytometry. Circulating antibody-secreting cells were enumerated using ELISpot assay. Serum was analyzed by ELISA using an antibody that recognizes products of the VH4-34 gene. Lymphocyte counts, Ig levels and anti-dsDNA antibody levels were available as part of the clinical trial analyses. Samples were collected at days 0, 84, 168, 365, 532 and >730. The total B cell number decreased from baseline starting between days 84–168. This was due to a decrease in naïve and transitional B cells. CD27+/IgD+memory B cells and plasmablasts decreased only after 532 days, whereas CD27+/IgD− memory B cells were not affected, and there were no changes in T cells. Serum IgM levels began to decline between days 84–168, but there were no changes in serum levels of IgG, IgG anti-DNA antibodies or VH4-34 antibodies during the study. SLE patients had more IgM-, IgG-, and autoantibody-producing B cells than normal controls at Day 0. There was only a modest decrease in the frequency of total IgM-producing but not IgG-producing cells at Days 365 and 532, consistent with the phenotypic and serologic data. Our data confirm the dependence of newly formed B cells on BLyS for survival in humans. In contrast, memory B cells and plasma cells are less susceptible to selective BLyS inhibition.
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影响因子：
15.3
作者：
Ngo, V N;Cornall, R J;Cyster, J G
通讯作者：
Cyster, J G
影响因子：
30.5
作者：
Doreau, Agnes;Belot, Alexandre;Bonnefoy-Berard, Nathalie
通讯作者：
Bonnefoy-Berard, Nathalie
影响因子：
15.9
作者：
Grammer, AC;Slota, R;Lipsky, PE
通讯作者：
Lipsky, PE
DOI：
10.1084/jem.20031330
发表时间：
2004-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
O'Connor BP;Raman VS;Erickson LD;Cook WJ;Weaver LK;Ahonen C;Lin LL;Mantchev GT;Bram RJ;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
--
作者：
Baker, KP;Edwards, BM;Albert, VR
通讯作者：
Albert, VR