Intrathyroidal fetal microchimerism in Graves' disease

During pregnancy, fetal cells are known to reach the maternal circulation and infiltrate a variety of tissues (fetal microchimerism). Although the presence of such cells has the potential to modulate the maternal immune response to both self antigens and fetal alloantigens, the degree of their influence remains unclear. The hyperthyroidism of Graves' disease frequently abates during pregnancy and exacerbates after childbearing. Thus, we have hypothesized that fetal cells in the maternal circulation and tissues may influence this decrescendo to crescendo pattern of autoimmune thyroid disease. Part of this hypothesis was tested using an ELISA-PCR for the detection of DNA for a male-specific gene, sex-determining region Y. The sensitivity of this assay was the equivalent of approximately 1 male cell among 10 female cells. We initially examined paraffin-embedded thyroid tissues and detected male cells in 4 of 20 female Graves' thyroid specimens, but not in 6 of 6 female adenoma specimens. Using frozen thyroid tissue specimens, an additional 6 of 7 Graves' disease samples demonstrated intrathyroidal fetal microchimerism, whereas 1 of 4 female samples with thyroid nodules showed male cells. The greater detection of the sex-determining region Y gene in frozen female thyroid tissues was probably due to DNA fragmentation in the paraffin-derived samples. In summary, we demonstrated that intrathyroidal fetal microchimerism was common and profound in female patients with Graves' disease. Thus, fetal male cells are valid candidates for modulating autoimmune thyroid disease in pregnancy and postpartum.