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      Fetal Microchimeric Cells in Blood of Women with an Autoimmune Thyroid Disease

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          Abstract

          Context

          Hashimoto's thyroiditis (HT) and Graves' disease (GD), two autoimmune thyroid diseases (AITD), occur more frequently in women than in men and show an increased incidence in the years following parturition. Persisting fetal cells could play a role in the development of these diseases.

          Objective

          Aim of this study was to detect and characterize fetal cells in blood of postpartum women with and without an AITD.

          Participants

          Eleven patients with an AITD and ten healthy volunteers, all given birth to a son maximum 5 years before analysis, and three women who never had been pregnant, were included. None of them had any other disease of the thyroid which could interfere with the results obtained.

          Methods

          Fluorescence in situ hybridization (FISH) and repeated FISH were used to count the number of male fetal cells. Furthermore, the fetal cells were further characterized.

          Results

          In patients with HT, 7 to 11 fetal cells per 1.000.000 maternal cells were detected, compared to 14 to 29 fetal cells in patients with GD ( p = 0,0061). In patients with HT, mainly fetal CD8 + T cells were found, while in patients with GD, fetal B and CD4 + T cells were detected. In healthy volunteers with son, 0 to 5 fetal cells were observed, which was significantly less than the number observed in patients ( p<0,05). In women who never had been pregnant, no male cells were detected.

          Conclusion

          This study shows a clear association between fetal microchimeric cells and autoimmune thyroid diseases.

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          Most cited references28

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          Clinical practice. Graves' disease.

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            Chronic autoimmune thyroiditis.

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              Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum.

              Rare nucleated fetal cells circulate within maternal blood. Noninvasive prenatal diagnosis by isolation and genetic analysis of these cells is currently being undertaken. We sought to determine if genetic evidence existed for persistent circulation of fetal cells from prior pregnancies. Venous blood samples were obtained from 32 pregnant women and 8 nonpregnant women who had given birth to males 6 months to 27 years earlier. Mononuclear cells were sorted by flow cytometry using antibodies to CD antigens 3, 4, 5, 19, 23, 34, and 38. DNA within sorted cells, amplified by PCR for Y chromosome sequences, was considered predictive of a male fetus or evidence of persistent male fetal cells. In the 32 pregnancies, male DNA was detected in 13 of 19 women carrying a male fetus. In 4 of 13 pregnancies with female fetuses, male DNA was also detected. All of the 4 women had prior pregnancies; 2 of the 4 had prior males and the other 2 had terminations of pregnancy. In 6 of the 8 nonpregnant women, male DNA was detected in CD34+CD38+ cells, even in a woman who had her last son 27 years prior to blood sampling. Our data demonstrate the continued maternal circulation of fetal CD34+ or CD34+CD38+ cells from a prior pregnancy. The prolonged persistence of fetal progenitor cells may represent a human analogue of the microchimerism described in the mouse and may have significance in development of tolerance of the fetus. Pregnancy may thus establish a long-term, low-grade chimeric state in the human female.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                27 December 2011
                : 6
                : 12
                : e29646
                Affiliations
                [1 ]Laboratory for Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium
                [2 ]Department of Endocrinology, University Hospital of Brussels (VUB), Brussels, Belgium
                [3 ]Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
                Cardiff University, United Kingdom
                Author notes

                Conceived and designed the experiments: TL MV KP BV JMK DD. Performed the experiments: TL SH. Analyzed the data: TL SH. Contributed reagents/materials/analysis tools: KP BV JMK DD. Wrote the paper: TL MV DD. Designed the software used in analysis: FVN. Revised manuscript: SH FVN KP BV JMK.

                Article
                PONE-D-11-21267
                10.1371/journal.pone.0029646
                3246474
                22216337
                29839692-5c89-4865-a1fb-8323f0eef22b
                Lepez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 27 October 2011
                : 2 December 2011
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Endocrine System
                Endocrine Physiology
                Thyroid
                Immunology
                Autoimmunity
                Medicine
                Anatomy and Physiology
                Endocrine System
                Endocrine Physiology
                Thyroid
                Clinical Immunology
                Autoimmune Diseases
                Graves' Disease
                Hashimoto Disease
                Endocrinology
                Endocrine Physiology
                Thyroid
                Thyroid
                Graves' Disease
                Hashimoto Disease
                Hypothyroidism
                Obstetrics and Gynecology
                Pregnancy

                Uncategorized
                Uncategorized

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