胎儿细胞微嵌合体：在自身免疫性甲状腺疾病中的保护作用。

Fetal cell microchimerism: a protective role in autoimmune thyroid diseases.

作者信息

Cirello Valentina, Rizzo Roberta, Crippa Milena, Campi Irene, Bortolotti Daria, Bolzani Silvia, Colombo Carla, Vannucchi Guia, Maffini Maria Antonia, de Liso Federica, Ferrero Stefano, Finelli Palma, Fugazzola Laura

机构信息

Endocrine UnitFondazione IRCCS Ca' Granda, Via F. Sforza, 35-20122 Milan, ItalyDepartment of Pathophysiology and TransplantationUniversity of Milan, Milan, ItalySection of Microbiology and Medical GeneticsDepartment of Medical Sciences, University of Ferrara, Ferrara, ItalyLaboratory of Medical Cytogenetics and Molecular GeneticsIstituto Auxologico Italiano, Milan, ItalyDepartment of Clinical Sciences and Community HealthUniversity of Milan, Milan, ItalyLaboratory of Clinical Chemistry and MicrobiologyFondazione IRCCS Ca' Granda, Milan, ItalyDivision of PathologyFondazione IRCCS Ca' Granda, Milan, ItalyDepartments of BiomedicalSurgical and Dental SciencesMedical Biotechnology and Translational MedicineUniversity of Milan, Milan, Italy Endocrine UnitFondazione IRCCS Ca' Granda, Via F. Sforza, 35-20122 Milan, ItalyDepartment of Pathophysiology and TransplantationUniversity of Milan, Milan, ItalySection of Microbiology and Medical GeneticsDepartment of Medical Sciences, University of Ferrara, Ferrara, ItalyLaboratory of Medical Cytogenetics and Molecular GeneticsIstituto Auxologico Italiano, Milan, ItalyDepartment of Clinical Sciences and Community HealthUniversity of Milan, Milan, ItalyLaboratory of Clinical Chemistry and MicrobiologyFondazione IRCCS Ca' Granda, Milan, ItalyDivision of PathologyFondazione IRCCS Ca' Granda, Milan, ItalyDepartments of BiomedicalSurgical and Dental SciencesMedical Biotechnology and Translational MedicineUniversity of Milan, Milan, Italy.

出版信息

Eur J Endocrinol. 2015 Jul;173(1):111-8. doi: 10.1530/EJE-15-0028. Epub 2015 Apr 27.

DOI:10.1530/EJE-15-0028

PMID:25916393

Abstract

OBJECTIVE

The physiological persistence of fetal cells in the circulation and tissue of a previously pregnant woman is called fetal cell microchimerism (FCM). It has been hypothesized to play a role in systemic autoimmune disease; however, only limited data are available regarding its role in autoimmune thyroid disease (AITD).

DESIGN

Circulating FCM was analyzed in a large series of previously pregnant women with Graves' disease (GD), Hashimoto's thyroiditis (HT), or no disease (healthy controls (HCs)). To exclude the possible bias related to placental factors, the polymorphic pattern of human leukocyte antigen-G (HLA-G) gene, which is known to be involved in the tolerance of fetal cells by the maternal immune system, was investigated.

METHODS

FCM was evaluated by PCR in the peripheral blood, and the Y chromosome was identified by fluorescence in situ hybridization in some GD tissues. HLA-G polymorphism typing was assessed by real-time PCR.

RESULTS

FCM was significantly more frequent in HC (63.6%) than in GD (33.3%) or HT (27.8%) women (P=0.0004 and P=0.001 respectively). A quantitative analysis confirmed that circulating male DNA was more abundant in HC than it was in GD or HT. Microchimeric cells were documented in vessels and in thyroid follicles. In neither GD/HT patients nor HC women was the HLA-G typing different between FCM-positive and FCM-negative cases.

CONCLUSION

The higher prevalence of FCM in HC as compared to GD and HT patients suggests that it plays a possible protective role in autoimmune thyroid disorders. Placental factors have been excluded as determinants of the differences found. The vascular and tissue localization of microchimeric cells further highlights the ability of those cells to migrate to damaged tissues.

摘要

目的

胎儿细胞在既往怀孕女性的循环系统和组织中的生理性持续存在被称为胎儿细胞微嵌合体（FCM）。据推测，它在系统性自身免疫性疾病中发挥作用；然而，关于其在自身免疫性甲状腺疾病（AITD）中的作用，仅有有限的数据。

设计

对大量患有格雷夫斯病（GD）、桥本甲状腺炎（HT）或无疾病（健康对照（HC））的既往怀孕女性进行循环FCM分析。为排除与胎盘因素相关的可能偏倚，研究了已知参与母体免疫系统对胎儿细胞耐受性的人类白细胞抗原-G（HLA-G）基因的多态性模式。

方法

通过PCR在外周血中评估FCM，并在一些GD组织中通过荧光原位杂交鉴定Y染色体。通过实时PCR评估HLA-G多态性分型。

结果

HC女性（63.6%）中FCM的发生率显著高于GD女性（33.3%）或HT女性（27.8%）（分别为P = 0.0004和P = 0.001）。定量分析证实，HC中循环男性DNA比GD或HT中更丰富。在血管和甲状腺滤泡中记录到微嵌合体细胞。在GD/HT患者和HC女性中，FCM阳性和FCM阴性病例之间的HLA-G分型均无差异。