Prolonged effects of short-term anti-CD20 B cell depletion therapy in murine systemic lupus erythematosus.
Prolonged effects of short-term anti-CD20 B cell depletion therapy in murine systemic lupus erythematosus.
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DOI：
10.1002/art.27515
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发表时间：
2010-08
影响因子：
--
通讯作者：
Anolik, Jennifer H.
中科院分区：
文献类型：
--
作者：
Bekar, Kai W.;Owen, Teresa;Dunn, Robert;Ichikawa, Travis;Wang, Wensheng;Wang, Roger;Barnard, Jennifer;Brady, Sean;Nevarez, Sarah;Goldman, Bruce I.;Kehry, Marilyn;Anolik, Jennifer H.
尽管B细胞与系统性红斑狼疮（SLE）的发病机制有关，但鉴于B细胞消耗（BCD）在人类疾病中的不同益处，其作为一种治疗方法的作用仍存在争议。BCD小鼠狼疮模型的建立将有助于更好地了解其机制、异质性及其对疾病预后的影响。不同疾病严重程度的NZB/NZWF1雌性小鼠接受抗cd20抗体（IgG2a）、BR3-Fc或对照抗体（10 mg/kg）。采集组织，流式细胞术分析。蛋白尿（Uristix）和肾免疫组化（IHC）监测肾炎。ELISA法检测血清免疫球蛋白水平。单次注射抗mcd20 B细胞后，正常小鼠以及年轻和患病狼疮小鼠的外周血、淋巴结和脾脏的细胞耗损比骨髓和腹膜更有效。由于边缘区和腹膜B细胞的消耗是不完全和可变的，特别是在患有肾炎的老年小鼠中，因此随后采用连续的每周给药策略以改善消耗。BAFF阻断进一步增强了脾脏和淋巴结的衰竭。早期BCDT延缓了疾病的发作，而晚期疾病小鼠的BCDT则减少了肾炎的进展。即使在B细胞重构发生后，这些影响仍是持久的，并且与T细胞活化的减少有关，但自身抗体的产生没有显著变化。短期BCD对具有完整免疫系统和既定疾病的狼疮易感小鼠的持久益处突出了这种治疗方法的有效性。
Although B cells are implicated in the pathogenesis of systemic lupus erythematosus (SLE), the role of B cell depletion (BCD) as a treatment is controversial given the variable benefit in human disease. The development of a murine lupus model of BCD would be helpful to better understand mechanisms, heterogeneity, and effects on disease outcomes. NZB/NZWF1 female mice of varying disease severity received anti-CD20 antibody (IgG2a), BR3-Fc, or control antibody (10 mg/kg). Tissues were harvested and analyzed by flow cytometry. Nephritis was monitored by proteinuria (Uristix) and kidney IHC. Serum immunoglobulin levels were measured by ELISA. After a single injection of anti-mCD20 B cell depletion was more efficient in peripheral blood, lymph node, and spleen compared to the bone marrow and peritoneum in normal mice as well as in young and diseased lupus mice. Since depletion of the marginal zone and peritoneal B cells was incomplete and variable particularly in older mice with established nephritis, a sequential weekly dosing strategy was subsequently used with improved depletion. BAFF blockade further enhanced depletion in spleen and lymph node. Early BCDT delayed disease onset, whereas BCDT in mice with advanced disease reduced the progression of nephritis. These effects were long-lasting even after B cell reconstitution occurred and associated with a reduction in T cell activation but no significant change in autoantibody production. The lasting benefit of a short course of BCD in lupus prone mice with an intact immune system and established disease highlights the validity of this treatment approach.
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影响因子：
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作者：
Leandro, MJ;Edwards, JC;Isenberg, DA
通讯作者：
Isenberg, DA
DOI：
10.4049/jimmunol.0803052
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Blair PA;Chavez-Rueda KA;Evans JG;Shlomchik MJ;Eddaoudi A;Isenberg DA;Ehrenstein MR;Mauri C
通讯作者：
Mauri C
影响因子：
--
作者：
Looney, RJ;Anolik, JH;Sanz, I
通讯作者：
Sanz, I
影响因子：
4.4
作者：
Hamaguchi, Y;Uchida, J;Tedder, TF
通讯作者：
Tedder, TF
影响因子：
15.9
作者：
Hu, Chang-Yun;Rodriguez-Pinto, Daniel;Wen, Li
通讯作者：
Wen, Li