Thymus Transplantation for Complete Digeorge Syndrome: European Experience

Publication date: Available online 8 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): E Graham Davies, Melissa Cheung, Kimberly Gilmour, Jesmeen Maimaris, Joe Curry, Anna Furmanski, Neil Sebire, Neil Halliday, Konstantinos Mengrelis, Stuart Adams, Jolanta Bernatoniene, Ronald Bremner, Michael Browning, Blythe Devlin, Hans Christian Erichsen, H Bobby Gaspar, Lizzie Hutchison, Winnie Ip, Marianne Ifversen, T Ronan Leahy, Elizabeth McCarthy, Despina Moshous, Kim Neuling, Malgorzata Pac, Alina Papadopol, Kathryn L. Parsley, Luigi Poliani, Ida Ricciardelli, David M. Sansom, Tiia Voor, Austen Worth, Tessa Crompton, M Louise Markert, Adrian J. Thrasher
BackgroundThymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS).MethodsTwelve patients with cDGS were transplanted with allogeneic cultured thymus.ObjectiveTo confirm and extend the results previously obtained in a single centre.ResultsTwo patients died of pre-existing viral infections without developing thymopoeisis and one late death occurred from autoimmune thrombocytopaenia. One infant suffered septic shock shortly after transplant resulting in graft loss and the need for a second transplant. Evidence of thymopoeisis developed from 5-6 months after transplantation in ten patients. The median (range) of circulating naïve CD4 counts (x10⁶/L) were 44(11-440) and 200(5-310) at twelve and twenty-four months post-transplant and T-cell receptor excision circles were 2238 (320-8807) and 4184 (1582 -24596) per10⁶ T-cells. Counts did not usually reach normal levels for age but patients were able to clear pre-existing and later-acquired infections. At a median of 49 months (22-80), eight have ceased prophylactic antimicrobials and five immunoglobulin replacement. Histological confirmation of thymopoeisis was seen in seven of eleven patients undergoing biopsy of transplanted tissue including five showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator (AIRE) expression was also demonstrated. Autoimmune complications were seen in 7/12 patients. In two, early transient autoimmune haemolysis settled after treatment and did not recur. The other five suffered ongoing autoimmune problems including: thyroiditis (3); haemolysis (1), thrombocytopaenia (4) and neutropenia (1).ConclusionsThis study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors.

Teaser

In twelve patients with complete DiGeorge syndrome treated with thymus transplantation, there was a 75% survival with T-cell reconstitution. Autoimmunity, mostly manageable, was a frequent occurrence in survivors.


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