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Correction of both immunodeficiency and hypoparathyroidism by thymus transplantation in complete DiGeorge syndrome
Authors:Alexandra Y. Kreins  Florence Junghanns  William Mifsud  Kathy Somana  Neil Sebire  Dyanne Rampling  Austen Worth  Methap Sirin  Catharina Schuetz  Ansgar Schulz  Manfred Hoenig  Adrian J. Thrasher  Edward G. Davies
Abstract:Combined immune deficiency due to athymia in patients with complete DiGeorge syndrome can be corrected by allogeneic thymus transplantation. Hypoparathyroidism is a frequent concomitant clinical problem in these patients, which persists after thymus transplantation. Cotransplantation of allogeneic thymus and parental parathyroid tissue has been attempted but does not achieve durable correction of the patients' hypoparathyroidism due to parathyroid graft rejection. Surprisingly, we observed correction of hypoparathyroidism in one patient after thymus transplantation. Immunohistochemical analysis and fluorescence in situ hybridization confirmed the presence of allogeneic parathyroid tissue in the patient's thymus transplant biopsy. Despite a lack of HLA‐matching between thymus donor and recipient, the reconstituted immune system displays tolerance toward the thymus donor. Therefore we expect this patient's hypoparathyroidism to be permanently cured. It is recognised that ectopic parathyroid tissue is not infrequently found in the thymus. If such thymuses could be identified, we propose that their use would offer a compelling approach to achieving lasting correction of both immunodeficiency and hypoparathyroidism.
Keywords:clinical research/practice  endocrinology/diabetology  immune deficiency  immunobiology  major histocompatibility complex  thymus/thymic biology  tolerance: mechanisms  translational research/science
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