Thymus transplantation for complete DiGeorge syndrome: European experience.

Published

Journal Article

Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS).Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus.We sought to confirm and extend the results previously obtained in a single center.Two patients died of pre-existing viral infections without having thymopoiesis, and 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting in graft loss and the need for a second transplant. Evidence of thymopoiesis developed from 5 to 6 months after transplantation in 10 patients. Median circulating naive CD4 counts were 44 × 106/L (range, 11-440 × 106/L) and 200 × 106/L (range, 5-310 × 106/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/106 T cells (range, 320-8,807/106 T cells) and 4,184/106 T cells (range, 1,582-24,596/106 T cells). Counts did not usually reach normal levels for age, but patients were able to clear pre-existing infections and those acquired later. At a median of 49 months (range, 22-80 months), 8 have ceased prophylactic antimicrobials, and 5 have ceased immunoglobulin replacement. Histologic confirmation of thymopoiesis was seen in 7 of 11 patients undergoing biopsy of transplanted tissue, including 5 showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator expression was also demonstrated. Autoimmune complications were seen in 7 of 12 patients. In 2 patients early transient autoimmune hemolysis settled after treatment and did not recur. The other 5 experienced ongoing autoimmune problems, including thyroiditis (3), hemolysis (1), thrombocytopenia (4), and neutropenia (1).This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors.

Full Text

Duke Authors

Cited Authors

  • Davies, EG; Cheung, M; Gilmour, K; Maimaris, J; Curry, J; Furmanski, A; Sebire, N; Halliday, N; Mengrelis, K; Adams, S; Bernatoniene, J; Bremner, R; Browning, M; Devlin, B; Erichsen, HC; Gaspar, HB; Hutchison, L; Ip, W; Ifversen, M; Leahy, TR; McCarthy, E; Moshous, D; Neuling, K; Pac, M; Papadopol, A; Parsley, KL; Poliani, L; Ricciardelli, I; Sansom, DM; Voor, T; Worth, A; Crompton, T; Markert, ML; Thrasher, AJ

Published Date

  • December 2017

Published In

Volume / Issue

  • 140 / 6

Start / End Page

  • 1660 - 1670.e16

PubMed ID

  • 28400115

Pubmed Central ID

  • 28400115

Electronic International Standard Serial Number (EISSN)

  • 1097-6825

International Standard Serial Number (ISSN)

  • 0091-6749

Digital Object Identifier (DOI)

  • 10.1016/j.jaci.2017.03.020

Language

  • eng