Thymus transplantation can be used to treat infants with DiGeorge syndrome, which results in an absent or hypoplastic thymus, in turn causing problems with the immune system's T-cell mediated response. It is exclusively used in people with complete DiGeorge anomaly, which are entirely athymic. This subgroup represents less than 1% of DiGeorge syndrome patients.
Nezelof syndrome is another thymus-related disease where it can be used.
Effects and prognosis
A study of 54 DiGeorge syndrome infants resulted in all tested subjects having developed polyclonal T-cell repertoires and proliferative responses to mitogens. The procedure was well tolerated and resulted in stable immunoreconstitution in these infants. It had a survival rate of 75%, having a follow-up as long as 13 years.
Complications include an increased susceptibility to infections while the T cells have not yet developed, rashes and erythema.
Theoretically, thymus transplantation could cause two types of graft-versus-host disease (GVHD): First, it could cause a donor T cell-related GVHD, because of T cells from the donor that are present in the transplanted thymus that recognizes the recipient as foreign. Donor T cells can be detected in the recipient after transplantation, but there is no evidence of any donor T cell-related graft-versus-host disease.
Second, a thymus transplantation can cause a non-donor T cell-related GVHD because the recipients thymocytes would use the donor thymus cells as models when going through the negative selection to recognize self-antigens, and could therefore still mistake own structures in the rest of the body for being non-self. This is a rather indirect GVHD because it is not directly cells in the graft itself that causes it, but cells in the graft that make the recipient's T cells act like donor T cells. It would also be of relatively late-onset because it requires the formation of new T cells. It can be seen as a multiple-organ autoimmunity in xenotransplantation experiments of the thymus between different species. Autoimmune disease is a frequent complication after human allogeneic thymus transplantation, found in 42% of subjects over 1 year post transplantation. However, this is partially explained by that the indication itself, that is, complete DiGeorge syndrome, increases the risk of autoimmune disease.
- Markert ML, Devlin BH, Alexieff MJ, et al. (May 2007). "Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants". Blood. 109 (10): 4539–47. doi:10.1182/blood-2006-10-048652. PMC 1885498. PMID 17284531.
- Markert ML, Boeck A, Hale LP, et al. (October 1999). "Transplantation of thymus tissue in complete DiGeorge syndrome". N. Engl. J. Med. 341 (16): 1180–9. doi:10.1056/NEJM199910143411603. PMID 10523153.
- Xia G, Goebels J, Rutgeerts O, Vandeputte M, Waer M (February 2001). "Transplantation tolerance and autoimmunity after xenogeneic thymus transplantation". J. Immunol. 166 (3): 1843–54. doi:10.4049/jimmunol.166.3.1843. PMID 11160231.
- Thymus Transplantation Book Thymus Gland Pathology Publisher Springer Milan DOI 10.1007/978-88-470-0828-1 Copyright 2008 ISBN 978-88-470-0827-4 (Print) 978-88-470-0828-1 (Online) DOI 10.1007/978-88-470-0828-1_30 Pages 255-267