[Characteristics of distribution and quantity of dendritic cells subtypes in hyperplastic thymus in patients with myasthenia gravis]

Zhonghua Yi Xue Za Zhi. 2017 May 23;97(19):1463-1468. doi: 10.3760/cma.j.issn.0376-2491.2017.19.008.
[Article in Chinese]

Abstract

Objective: To investigate the characteristics of the distribution and amount of different subtypes of dendritic cell (DC) in myasthenia gravis(MG). Methods: We collected the thymic specimens from 32 patients who received thymoctomy because of cardiac surgery from January 2016 to December 2016 and selected 14 of them as normal control. Meantime, 61 MG patients who combined with thymic hyperplasia and received extended thymectomy were collected and selected 8 of them as experiment group.Immunohistochemical methods were used to label the two subtype DCs: plasmacytoid dendritic cell (pDC) and classical/conventional dendritic cell (cDC), to observe the distribution of these two DC subtypes in thymus and also quantify them in different thymus structures by image analysis software.Comparing with normal thymus of the same age, we intended to demonstrate the characteristics of distribution and density of DC subtypes in patients who had MG and hyperplastic thymus. Results: (1) We labeled pDC and cDC by staining with CD123 and CD11c.The two DC subtypes distributed in both cortex and medulla, and the majority gathered in medulla, the density of pDC in thymus cortex was (34±6)/mm(2)(n=14), the density of pDC in thymus medulla was (247±35)/mm(2)(n=14), the density of cDC in thymus cortex was (21±4)/mm(2)(n=14), the density of cDC in thymus medulla was (123±16)/mm(2) (n=14). (2) The density of pDC in thymus cortex and medulla of patients with MG was lower when compared with the normal group (the density of pDC in thymus cortex, [(39±10)/mm(2) vs (29±5)/mm(2)], the density of pDC in thymus medulla, [(279±48)/mm(2) vs (236±49)/mm(2)], but with no significant difference.There was no significant difference between the density of cDC in thymus cortex of patients with MG patients and normal people, however, the amount of cDC increases in medulla and the difference was statistically significant (P<0.05). (3) The density of cDC in thymus medulla (except for germinal center) was higher than normal people (110±18) /mm(2) vs (187±29/mm(2)), though the difference was not statistically significant (P=0.059 9). The density of cDC in the ectopic germinal center (GC) of MG patients increased obviously compared with that in thymus medulla [(203±44) /mm(2) vs (439±69)/mm(2)] and the difference was statistically significant (P<0.05). Conclusions: The density of cDC increases significantly in thymus medulla of MG patients, especially gathering around or in the ectopic GC. It indicates that cDC may play an important role in the formation of ectopic GC in the hyperplasia thymus, thus involves in the disease process.

目的: 探讨胸腺中树突状细胞(DC)的不同亚型分布和数量的特点及其与重症肌无力(MG)发生的相关性。 方法: 收集2016年1—12月在中山大学附属第一医院因心脏手术需行胸腺切除的32例患者的胸腺标本,并选取其中14例病人胸腺标本作为正常对照组;同时收集合并胸腺增生并行胸腺扩大切除术的61例MG患者胸腺标本,并选取其中8例作为MG组。利用免疫酶组织化学方式标记DC的两种亚型:浆细胞样树突状细胞(pDC)和经典树突状细胞(cDC);观察两种DC亚型在胸腺中的分布情况;通过使用图像分析软件,统计DC亚型在不同胸腺结构中的数量,并计算其相应的密度;通过与同年龄段正常胸腺的比较,阐明MG患者增生胸腺中DC亚型的分布和密度特点。 结果: (1)通过CD123和CD11c染色可分别标记pDC和cDC这两种DC的亚型;对照组两种DC亚型在皮质和髓质均有分布,但大多数分布于髓质区[胸腺皮质中pDC的密度为(34±6)/mm(2)(n=14),髓质中pDC的密度为(247±35)/mm(2)(n=14);皮质中cDC的密度为(21±4)/mm(2)(n=14),髓质中cDC密度为(123±16)/mm(2)(n=14)]。(2)MG患者胸腺皮髓质中pDC的密度较正常组低[皮质pDC:(39±10) /mm(2)比(29±5)/mm(2);髓质pDC:(279±48)/mm(2)比(236±49)/mm(2)];MG患者胸腺皮质中cDC的密度与正常对照组无明显差异[(17±6)/mm(2) 比(21±6)/mm(2)];但髓质中cDC升高[(110±18)/mm(2)比(194±28)/mm(2)],两者差异有统计学意义(P<0.05)。(3)MG患者胸腺髓质(除去生发中心)的cDC密度高于对照组胸腺髓质[(110±18)/mm(2) 比(187±29)/mm(2)],但差异无统计学意义(P=0.059 9);MG患者胸腺生发中心的cDC密度较胸腺髓质平均cDC明显增高[(203±44)/mm(2) 比439±69/mm(2)],且差异有统计学意义(P<0.05)。 结论: MG患者胸腺髓质中cDC密度明显增高,尤其集中于异位生发中心中及其周围,这提示cDC可能在MG"病灶"的形成和维持中起重要作用。.

Keywords: Conventional dendritic cell; Myasthenia gravis; Plasmacytoid dendritic cell; Thymus.

MeSH terms

  • Dendritic Cells*
  • Humans
  • Myasthenia Gravis / pathology*
  • Myasthenia Gravis / therapy
  • Thymectomy
  • Thymus Gland
  • Thymus Hyperplasia / surgery*