Thymus transplantation for complete DiGeorge syndrome: European experience

被引：100

作者：

Davies, E. Graham ^{[1
,2
]}

Cheung, Melissa ^{[1
]}

Gilmour, Kimberly ^{[2
]}

Maimaris, Jesmeen ^{[1
]}

Curry, Joe ^{[2
]}

Furmanski, Anna ^{[1
,3
]}

Sebire, Neil ^{[2
]}

Halliday, Neil ^{[4
]}

Mengrelis, Konstantinos ^{[1
]}

Adams, Stuart ^{[2
]}

Bernatoniene, Jolanta ^{[5
]}

Bremner, Ronald ^{[6
]}

Browning, Michael ^{[7
]}

Devlin, Blythe ^{[8
]}

Erichsen, Hans Christian ^{[9
]}

Gaspar, H. Bobby ^{[1
,2
]}

Hutchison, Lizzie ^{[5
]}

Ip, Winnie ^{[1
,2
]}

Ifversen, Marianne ^{[10
]}

Leahy, T. Ronan ^{[11
]}

McCarthy, Elizabeth ^{[8
]}

Moshous, Despina ^{[12
]}

Neuling, Kim ^{[13
]}

Pac, Malgorzata ^{[14
]}

Papadopol, Alina ^{[15
]}

Parsley, Kathryn L. ^{[1
,2
]}

Poliani, Luigi ^{[16
]}

Ricciardelli, Ida ^{[1
]}

Sansom, David M. ^{[4
]}

Voor, Tiia ^{[17
]}

Worth, Austen ^{[1
,2
]}

Crompton, Tessa ^{[1
]}

Markert, M. Louise ^{[7
]}

Thrasher, Adrian J. ^{[1
]}

机构：

[1] UCL Great Ormond St Inst Child Hlth, Infect Immun & Inflammat Theme, London, England

[2] Great Ormond St Hosp Sick Children, Dept Immunol, London, England

[3] Univ Bedfordshire, Sch Life Sci, Luton, Beds, England

[4] UCL, Inst Immun & Transplantat, Sch Life & Med Sci, Div Infect & Immun,Royal Free Hosp, London, England

[5] Bristol Childrens Hosp, Dept Paediat Immunol & Infect Dis, Bristol, Avon, England

[6] Birmingham Childrens Hosp, Dept Gastroenterol, Birmingham, W Midlands, England

[7] Leicester Royal Infirm, Dept Immunol, Leicester, Leics, England

[8] Duke Univ, Div Allergy & Immunol, Dept Pediat, Med Ctr, Durham, NC 27706 USA

[9] Oslo Univ Hosp, Div Paediat & Adolescent Med, Sect Paediat Med & Transplantat, Oslo, Norway

[10] Copenhagen Univ Hosp, Rigshosp, Paediat Clin 2, Copenhagen, Denmark

[11] Our Ladys Childrens Hosp, Dept Paediat Immunol & Infect Dis, Dublin, Ireland

[12] Hop Necker Enfants Malad, Paediat Immunol Haematol & Rheumatol Unit, Paris, France

[13] Univ Hosp, Dept Paediat, Coventry, W Midlands, England

[14] Childrens Mem Hlth Inst, Dept Immunol, Warsaw, Poland

[15] Polyclin Regina Maria Baneasa, Paediat Clin, Bucharest, Romania

[16] Univ Brescia, Inst Immun & Translat Med, Brescia, Italy

[17] Tartu Univ Hosp, Childrens Clin, Tartu, Estonia

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2017年 / 140卷 / 06期

基金：

英国惠康基金;

关键词：

DiGeorge syndrome; athymia; thymus transplantation; T-CELLS; AUTOIMMUNE REGULATOR; RECONSTITUTION;

D O I：

10.1016/j.jaci.2017.03.020

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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 x 10(6)/L (range, 11-440 x 10(6)/L) and 200 x 10(6)/L (range, 5-310 x 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.

引用

页码：1660 / +

页数：27

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