Thymus transplantation for complete digeorge syndrome: European experience

2.50
Hdl Handle:
http://hdl.handle.net/10547/622087
Title:
Thymus transplantation for complete digeorge syndrome: European experience
Authors:
Davies E Graham; Cheung, Melissa; Gilmour, Kimberly; Maimaris, Jesmeen; Curry, Joe; Furmanski, Anna L.; Sebire, Neil; Halliday, Neil; Mengrelis, Konstantinos; Adams, Stuart; Bernatoniene, Jolanta; Bremner, Ronald; Browning, Michael; Devlin, Blythe; Erichsen, Hans Christian; Gaspar, H. Bobby; Hutchison, Lizzie; Ip, Winnie; Ifversen, Marianne; Leahy, T. Ronan; McCarthy, Elizabeth; Moshous, Despina; Neuling, Kim; Pac, Malgorzata; Papadopol, Alina; Parlsey, Kathryn L.; Poliani, Luigi; Ricciardelli, Ida; Sansom, David M.; Voor, Tiia; Worth, Austen; Crompton, Tessa ( 0000-0002-8973-4021 ) ; Markert, M. Louise; Thrasher, Adrian J.
Abstract:
Background: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Methods: Twelve patients with cDGS were transplanted with allogeneic cultured thymus. Objective: To confirm and extend the results previously obtained in a single centre. Results: Two 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 (x10663 /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 65 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). Conclusions: This study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors.
Affiliation:
University College London; Great Ormond Street Hospital; University of Bedfordshire; Royal Free Hospital; Bristol Children’s Hospital; Birmingham Children’s Hospital; Leicester Royal Infirmary; Duke University Medical Center; Oslo University Hospital; Copenhagen University Hospital; Our Lady’s Children’s Hospital, Dublin; Hopital Necker, Paris; University Hospital, Coventry; Children’s Memorial Health Institute, Warsaw; Paediatric Clinic, Bucharest; University of Brescia; Tartu University Hospital
Citation:
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, Parlsey KL, Poliani L, Ricciardelli I, Sansom DM, Voor T, Worth A, Crompton T, Markert ML, Thrasher AJ (2017) 'Thymus transplantation for complete digeorge syndrome: European experience', Journal of Allergy and Clinical Immunology.
Publisher:
Elsevier
Journal:
Journal of Allergy and Clinical Immunology
Issue Date:
1-Apr-2017
URI:
http://hdl.handle.net/10547/622087
DOI:
10.1016/j.jaci.2017.03.020
Additional Links:
http://www.jacionline.org/article/S0091-6749(17)30576-6/abstract; http://www.sciencedirect.com/science/article/pii/S0091674917305766
Type:
Article
Language:
en
ISSN:
0091-6749
Sponsors:
The research leading to these results has received funding from: European Union Seventh Framework Programme ([FP7/2007-2013] [FP7/2007-2011]) under grant agreement N° 261387; Great Ormond Street Hospital Children’s Charity, Mason Medical Research Fund, Wellcome Trust.The work reported is based on independent research, partly supported by the National Institute for Health Research, Great Ormond Street Hospital Biomedical Research Centre (KG, EGD, AJT).
Appears in Collections:
Biomedical and biological science

Full metadata record

DC FieldValue Language
dc.contributor.authorDavies E Grahamen
dc.contributor.authorCheung, Melissaen
dc.contributor.authorGilmour, Kimberlyen
dc.contributor.authorMaimaris, Jesmeenen
dc.contributor.authorCurry, Joeen
dc.contributor.authorFurmanski, Anna L.en
dc.contributor.authorSebire, Neilen
dc.contributor.authorHalliday, Neilen
dc.contributor.authorMengrelis, Konstantinosen
dc.contributor.authorAdams, Stuarten
dc.contributor.authorBernatoniene, Jolantaen
dc.contributor.authorBremner, Ronalden
dc.contributor.authorBrowning, Michaelen
dc.contributor.authorDevlin, Blytheen
dc.contributor.authorErichsen, Hans Christianen
dc.contributor.authorGaspar, H. Bobbyen
dc.contributor.authorHutchison, Lizzieen
dc.contributor.authorIp, Winnieen
dc.contributor.authorIfversen, Marianneen
dc.contributor.authorLeahy, T. Ronanen
dc.contributor.authorMcCarthy, Elizabethen
dc.contributor.authorMoshous, Despinaen
dc.contributor.authorNeuling, Kimen
dc.contributor.authorPac, Malgorzataen
dc.contributor.authorPapadopol, Alinaen
dc.contributor.authorParlsey, Kathryn L.en
dc.contributor.authorPoliani, Luigien
dc.contributor.authorRicciardelli, Idaen
dc.contributor.authorSansom, David M.en
dc.contributor.authorVoor, Tiiaen
dc.contributor.authorWorth, Austenen
dc.contributor.authorCrompton, Tessaen
dc.contributor.authorMarkert, M. Louiseen
dc.contributor.authorThrasher, Adrian J.en
dc.date.accessioned2017-04-20T10:46:35Z-
dc.date.available2017-04-20T10:46:35Z-
dc.date.issued2017-04-01-
dc.identifier.citationDavies 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, Parlsey KL, Poliani L, Ricciardelli I, Sansom DM, Voor T, Worth A, Crompton T, Markert ML, Thrasher AJ (2017) 'Thymus transplantation for complete digeorge syndrome: European experience', Journal of Allergy and Clinical Immunology.en
dc.identifier.issn0091-6749-
dc.identifier.doi10.1016/j.jaci.2017.03.020-
dc.identifier.urihttp://hdl.handle.net/10547/622087-
dc.description.abstractBackground: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Methods: Twelve patients with cDGS were transplanted with allogeneic cultured thymus. Objective: To confirm and extend the results previously obtained in a single centre. Results: Two 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 (x10663 /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 65 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). Conclusions: This study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors.en
dc.description.sponsorshipThe research leading to these results has received funding from: European Union Seventh Framework Programme ([FP7/2007-2013] [FP7/2007-2011]) under grant agreement N° 261387; Great Ormond Street Hospital Children’s Charity, Mason Medical Research Fund, Wellcome Trust.The work reported is based on independent research, partly supported by the National Institute for Health Research, Great Ormond Street Hospital Biomedical Research Centre (KG, EGD, AJT).en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://www.jacionline.org/article/S0091-6749(17)30576-6/abstracten
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0091674917305766en
dc.rightsGreen - can archive pre-print and post-print or publisher's version/PDF-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDiGeorge syndromeen
dc.subjectathymiaen
dc.subjectthymus transplantationen
dc.subjectimmunologyen
dc.subjectC550 Immunologyen
dc.titleThymus transplantation for complete digeorge syndrome: European experienceen
dc.typeArticleen
dc.contributor.departmentUniversity College Londonen
dc.contributor.departmentGreat Ormond Street Hospitalen
dc.contributor.departmentUniversity of Bedfordshireen
dc.contributor.departmentRoyal Free Hospitalen
dc.contributor.departmentBristol Children’s Hospitalen
dc.contributor.departmentBirmingham Children’s Hospitalen
dc.contributor.departmentLeicester Royal Infirmaryen
dc.contributor.departmentDuke University Medical Centeren
dc.contributor.departmentOslo University Hospitalen
dc.contributor.departmentCopenhagen University Hospitalen
dc.contributor.departmentOur Lady’s Children’s Hospital, Dublinen
dc.contributor.departmentHopital Necker, Parisen
dc.contributor.departmentUniversity Hospital, Coventryen
dc.contributor.departmentChildren’s Memorial Health Institute, Warsawen
dc.contributor.departmentPaediatric Clinic, Bucharesten
dc.contributor.departmentUniversity of Bresciaen
dc.contributor.departmentTartu University Hospitalen
dc.identifier.journalJournal of Allergy and Clinical Immunologyen
dc.date.updated2017-04-20T10:24:15Z-
dc.description.noteOpen access funded by Wellcome Trust-
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