调节性B细胞在天疱疮患者外周血中的水平及临床意义

2017-07-17 许人超、潘萌 上海交通大学学报

许人超、潘萌,上海市嘉定区中心医院皮肤科 上海交通大学医学院附属瑞金医院皮肤科目的:探讨天疱疮患者外周血调节性B细胞的水平及其在天疱疮发病中的意义。方法:选取天疱疮患者40例,正常对照组 20例,抽取外周静脉血,流式细胞术检测外周血中CDl9+B细胞和刺激5 h、48 h后CDl9+IL·10+B细胞水平;酶联免疫吸附法检测血清中抗dsgl和抗ds93抗体滴度。结果:天疱疮患者外周血CDl9+B细

许人超、潘萌,上海市嘉定区中心医院皮肤科 上海交通大学医学院附属瑞金医院皮肤科


目的:探讨天疱疮患者外周血调节性B细胞的水平及其在天疱疮发病中的意义。


方法:选取天疱疮患者40例,正常对照组 20例,抽取外周静脉血,流式细胞术检测外周血中CDl9+B细胞和刺激5 h、48 h后CDl9+IL·10+B细胞水平;酶联免疫吸附法检测血清中抗dsgl和抗ds93抗体滴度。


结果:天疱疮患者外周血CDl9+B细胞比例与正常对照组差异无统计学意义(P>0.05),CDl9+ B细胞在急性发作期、慢性活动期及稳定期的天疱疮患者中差异亦无统计学意义(P>0.05)。体外刺激5 h后,天疱疮患者外周血 CDl9+IL一10+B细胞水平显著高于正常对照组(P=0.008),但在刺激48 h后,2组差异无统计学意义(P>0.05)。20例寻常型天疱疮患 者中,急性发作期和慢性活动期患者的抗ds93抗体滴度均显著高于稳定期患者(P<0.05);20例落叶型天疱疮患者中,急性发作期和慢性活动期患者的抗dsgI抗体滴度均显著高于稳定期患者(P<0.05)。


结论:天疱疮患者血清中致病性自身抗体滴度水平与B细胞数 量无关,与疾病活动期有关;天疱疮患者外周血调节性B细胞功能可能存在缺陷。


讨论:传统意义上的B细胞通过分泌抗体发挥致病作用,在 体液免疫中起主导地位。B细胞还可作为抗原递呈细胞 对CD4+T细胞发挥作用,促进原始CD4+T细胞向Thl或 Th2型细胞转化,并调节T细胞的功能。因此,B细胞可 以通过其细胞和体液免疫的双重调节功能对机体的各种免疫成分进行调节,在自身免疫性疾病中发挥正向致病作用。利妥昔单抗注射液是抗B细胞CD20抗原的单克隆 抗体,天疱疮患者使用后通过清除体内B细胞从而抑制抗体的产生,缓解疾病,进一步证实了B细胞的致病性。 本研究对天疱疮患者外周血CDl9+B细胞进行检测,发现患者和正常对照组CDl9+B细胞比例无明显差异,并且在 各疾病期患者中也无明显差异,说明疾病活动度与CDl9+ B细胞数目无相关性。


调节性B细胞是最近被发现的一群具有负向免疫调节作用的B细胞,目前已成为国际上新兴的研究热点。 Breg主要通过分泌IL一10发挥作用,但是近期也有研究 发现,除几IL一10外,Breg还可通过不依赖IL-10的途径发挥作用。在天疱疮患者中,通过利妥昔单抗治疗后达到完全缓解的患者,其外周血IL一10+Breg细胞水平是不完全缓解患者的4倍多,提示Breg细胞在天疱疮中的保护作用。本研究对天疱疮患者和正常对照组外周血 CDl9+IL-10+B细胞进行检测,发现在未刺激情况下,几乎检测不到CDl9+IL-10+B细胞,在体外经CpG、LPS和 CD40L刺激5 h后可检测到CDl9+IL一10+B细胞,并且在患者中比例显著高于正常对照组。在刺激48 h后,2组CDl9+IL.10+B细胞均显著升高,但正常对照组增高更为明显,其增高的倍数高于天疱疮患者。上述结果提示,天疱疮患者调节性B细胞分泌IL-10功能可能存在缺陷,从而不能有效发挥其免疫抑制作用,导致了疾病的产生,其具体作用机制需进一步研究。


天疱疮是抗体介导的以体液免疫为主的器官特异性自身免疫病的典型。将患者血清被动转移到新生鼠体内,新 生鼠出现了与患者一致的临床和组织病理改变,证明了天 疱疮自身抗体的致病性体水平存在相关性。本研究对40例天疱疮患者血 清中致病性抗dsgl和ds93抗体进行检查,发现PV患者中, 急性发作期和慢性活动期患者抗ds93抗体滴度显著高于 稳定期患者;PF患者中,急性发作期和慢性活动期患者抗 gl抗体滴度显著高于稳定期患者;说明疾病活动度与抗体水平存在相关性。


原始出处:


上海交通大学学报(医学版),2016,08:1154-1158.


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    2017-07-23 laoli

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    2017-07-19 松鼠上树

    学习了,谢谢分享

    0

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    2017-07-18 1e10c84am36(暂无匿称)

    文章不错,谢谢分享

    0

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    2017-07-18 清风拂面

    谢谢分享,学习了

    0

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    2017-07-18 189****7206

    学习了谢谢分享

    0

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