Correction of both immunodeficiency and hypoparathyroidism by thymus transplantation in complete DiGeorge syndrome.

clinical research/practice endocrinology/diabetology immune deficiency immunobiology major histocompatibility complex thymus/thymic biology tolerance: mechanisms translational research/science

Journal

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638

Informations de publication

Date de publication:
05 2020
Historique:
received: 23 08 2019
revised: 06 10 2019
accepted: 16 10 2019
pubmed: 31 10 2019
medline: 22 6 2021
entrez: 31 10 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31663273
doi: 10.1111/ajt.15668
pii: S1600-6135(22)22331-4
doi:

Types de publication

Case Reports Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1447-1450

Informations de copyright

© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.

Références

Davies EG, Cheung M, Gilmour K, et al. Thymus transplantation for complete DiGeorge syndrome: European experience. J Allergy Clin Immunol. 2017;140(6):1660-1670.
Markert ML, Devlin BH, Alexieff MJ, et al. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007;109(10):4539-4547.
Chinn IK, Markert ML. Induction of tolerance to parental parathyroid grafts using allogeneic thymus tissue in patients with DiGeorge anomaly. J Allergy Clin Immunol. 2011;127(6):1351-1355.
Brandi ML, Bilezikian JP, Shoback D, et al. Management of hypoparathyroidism: summary statement and guidelines. J Clin Endocrinol Metab. 2016;101(6):2273-2283.
US FDA. Natpara (parathyroid hormone) for injection: US prescribing information. 2015. https://www.fda.gov/media/91054/download November 12, 2019.
Garcia-Roca R, Garcia-Aroz S, Tzvetanov IG, et al. Simultaneous living donor kidney and parathyroid allotransplantation: first case report and review of literature. Transplantation. 2016;100(6):1318-1321.
Schneider R, Waldmann J, Ramaswamy A, Dominguez Fernandez E, Bartsch DK, Schlosser K. Frequency of ectopic and supernumerary intrathymic parathyroid glands in patients with renal hyperparathyroidism: analysis of 461 patients undergoing initial parathyroidectomy with bilateral cervical thymectomy. World J Surg. 2011;35:1260-1265.
Chinn IK, Devlin BH, Li YJ, Markert ML. Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly. Clin Immunol. 2008;126(3):277-281.

Auteurs

Alexandra Y Kreins (AY)

Great Ormond Street Hospital for Children NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, London, UK.

Florence Junghanns (F)

Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.

William Mifsud (W)

Great Ormond Street Hospital for Children NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, London, UK.

Kathy Somana (K)

Great Ormond Street Hospital for Children NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, London, UK.

Neil Sebire (N)

Great Ormond Street Hospital for Children NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, London, UK.

Dyanne Rampling (D)

Great Ormond Street Hospital for Children NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, London, UK.

Austen Worth (A)

Great Ormond Street Hospital for Children NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, London, UK.

Methap Sirin (M)

Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.

Catharina Schuetz (C)

Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.
Department of Pediatrics, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Ansgar Schulz (A)

Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.

Manfred Hoenig (M)

Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.

Adrian J Thrasher (AJ)

Great Ormond Street Hospital for Children NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, London, UK.

Edward G Davies (EG)

Great Ormond Street Hospital for Children NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, London, UK.

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