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


METHODS
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.


CONCLUSIONS
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.
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.
Valentina
V
Cirello
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.
Roberta
R
Rizzo
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.
Milena
M
Crippa
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.
Irene
I
Campi
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.
Daria
D
Bortolotti
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.
Silvia
S
Bolzani
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.
Carla
C
Colombo
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.
Guia
G
Vannucchi
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.
Maria Antonia
MA
Maffini
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.
Federica
F
de Liso
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.
Stefano
S
Ferrero
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.
Palma
P
Finelli
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 laura.fugazzola@unimi.it.
Laura
L
Fugazzola
D000328:Adult; D000369:Aged, 80 and over; D001808:Blood Vessels / Q000473:pathology; D046528:Chimerism / Q000196:embryology*; D041322:Chromosomes, Human, Y / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D005333:Fetus / Q000166:cytology*; D006111:Graves Disease / Q000235:genetics / Q000473:pathology; D059951:HLA-G Antigens / Q000235:genetics; D050031:Hashimoto Disease / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D013961:Thyroid Gland / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000235:genetics*
D059951:HLA-G Antigens; D004247:DNA