Thymus Transplantation for Complete Digeorge Syndrome: European Experience
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine T-Lymphocytes medicine.medical_treatment FoxP3 Forkhead box P3 Hematopoietic stem cell transplantation EpCam Epithelial cell adhesion molecule Autoimmune thrombocytopenia HSCT Hematopoietic stem cell transplantation Immune Reconstitution Postoperative Complications 0302 clinical medicine DiGeorge syndrome Immunology and Allergy thymus transplantation Child CTLA4 Cytotoxic T lymphocyte–associated antigen 4 Cells Cultured cTEC Cortical thymic epithelial cell AIRE Autoimmune regulator athymia FOXP3 Autoimmune regulator Europe ATG Antithymocyte globulin Treatment Outcome Thymus transplantation Child Preschool Female DGS DiGeorge syndrome CHARGE Coloboma heart defects atresia choanae retardation of growth and development genital abnormalities ear abnormalities/deafness Immunology Thymus Gland Biology Neutropenia Article Autoimmune Diseases 03 medical and health sciences Organ Culture Techniques mTEC Medullary thymic epithelial cell medicine Humans Transplantation Homologous LCL Lymphoblastoid cell line SCID Severe combined immunodeficiency CMV Cytomegalovirus TEC Thymic epithelial cell TREC T-cell receptor signal joint excision circle Infant cDGS Complete DiGeorge syndrome Organ Transplantation Treg Regulatory T medicine.disease Transplantation 030104 developmental biology TCR T-cell receptor CK Cytokeratin 030215 immunology |
| Zdroj: | Journal of Allergy and Clinical Immunology The Journal of Allergy and Clinical Immunology |
| Popis: | Background Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Methods Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus. Objective We sought to confirm and extend the results previously obtained in a single center. Results 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 × 10 6 /L (range, 11-440 × 10 6 /L) and 200 × 10 6 /L (range, 5-310 × 10 6 /L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/10 6 T cells (range, 320-8,807/10 6 T cells) and 4,184/10 6 T cells (range, 1,582-24,596/10 6 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). Conclusions This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors. |
| Databáze: | OpenAIRE |
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