B-cell activity in children with malaria
B-cell activity in children with malaria
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DOI：
10.1186/1475-2875-11-66
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发表时间：
2012-03-09
期刊：
影响因子：
3
通讯作者：
Waitumbi, John N.
中科院分区：
文献类型：
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作者：
Korir, Jackson C.;Magambo, Japhet K.;Waitumbi, John N.
背景：最近的研究表明红细胞 (RBC) 补体调节蛋白（CR1 和 CD55）的缺乏与疟疾贫血的发病机制有关。本研究探索了 B 细胞 CD21 的参与，其作用与 RBC CR1 类似。方法：在肯尼亚西部基苏木区医院进行的一项病例对照研究中，通过流式细胞术评估 B 细胞 (CD20+) 数量、CD21 表达水平和 C3dg 沉积，并通过 ELISA 评估可溶性 CD21 (sCD21)。使用配对 t 检验确定 a = 0.05 时的统计显着性。结果：SMA 儿童的淋巴细胞计数显着较高（UM 组为 9,627.7 +/- 8786.1 SD 对比 5,507 +/- 2436 SD，P = 0.04），并且根据绝对淋巴细胞计数计算出的成熟 B 细胞数量的几何平均值显着高于 SMA 组：1,823 UM 组为（1,126 至 2,982，95% CI）和 826.6（564 至 1,220，95% CI）（P = 0.003）。 SMA 组的 CD20+ B 细胞百分比也较高（UM 中为 26.8 +/- 9.7SD 对比 20.9 +/- 9.01 SD）（P = 0.03），表明多克隆 B 细胞活化相当多。 SMA 中的 CD21 中位荧光强度较低（246.4 +/- 87.4 SD vs 369 +/- 137.7 SD）（P < 0.0001），可能是由于固定组织巨噬细胞补体介导的 CD21 剃削所致。 SMA 的 CD20+ B 细胞具有较高水平的补体裂解产物 C3dg（18.35 +/- 10 SD vs 11.5 +/- 6.8 S.D），（P = 0.0002），证实了补体在 CD21 去除中的可能作用。出乎意料的是，SMA 的 sCD21 水平较低（UM 中为 226.5 +/- 131.5 SD 对比 341.4 +/- 137.3 SD）（P < 0.0001），表明被削去的 CD21 不会释放到外周循环。结论：这些结果表明 B 细胞参与严重疟疾的病理生理学，涉及 B 细胞增殖增加、补体沉积增加和随后的损失膜结合 CD21。 CD21 的丢失不是由经典的酶裂解引起的。
Background: Recent studies implicate deficiency of red blood cell (RBC) complement regulatory proteins (CR1 and CD55) in the pathogenesis of malarial anaemia. This study explored the involvement of B cell CD21, which has an analogous role to RBC CR1.Methods: In a case control study conducted in Kisumu District hospital, western Kenya, children with severe malaria anaemia (SMA) and those with uncomplicated malaria (UM) were assessed by flow cytometry for B cells (CD20+) numbers, expression levels of CD21 and deposition of C3dg and by ELISA for soluble CD21 (sCD21). Paired t tests were used to determine statistical significance at a = 0.05.Results: Children with SMA had significantly higher lymphocyte count (9,627.7 +/- 8786.1 SD vs. 5,507 +/- 2436 SD, P = 0.04 in the UM group) and the computed geometric mean of mature B-cell numbers based on the absolute lymphocyte count was significantly higher for SMA group: 1,823 (1,126 to 2,982, 95% CI) and 826.6 (564 to 1,220, 95% CI)] for UM group (P = 0.003). SMA group also had a higher percentage of CD20+ B cells (26.8 +/- 9.7SD vs 20.9 +/- 9.01 SD in the UM) (P = 0.03), indicating considerable polyclonal B-cell activation. The CD21 median flourescence intensity was lower in the SMA (246.4 +/- 87.4 SD vs 369 +/- 137.7 SD) (P < 0.0001), probably due to complement mediated shaving of CD21 by fixed tissue macrophages. The CD20+ B cells of SMAs had higher levels of the complement split product C3dg (18.35 +/- 10 SD vs 11.5 +/- 6.8 S. D), (P = 0.0002), confirming possible role of complement in CD21 removal. Unexpectedly, the SMAs had lower levels of sCD21 (226.5 +/- 131.5 SD vs 341.4 +/- 137.3 SD in the UM) (P < 0.0001), indicating that the shaved CD21 is not released to peripheral circulation.Conclusions: These results implicate B-cell in pathophysiology of severe malaria that involves increased B-cell proliferation, increased complement deposition and subsequent loss of membrane-bound CD21. The loss of CD21 is not by the classical enzmatic cleavage.