Factors affecting success of thymus transplantation for complete DiGeorge anomaly

被引:33
作者
Markert, M. L. [1 ,2 ]
Devlin, B. H. [1 ]
Chinn, I. K. [1 ]
McCarthy, E. A. [1 ]
Li, Y. J. [3 ]
机构
[1] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Med, Ctr Human Genet, Durham, NC 27710 USA
关键词
thymus; transplantation;
D O I
10.1111/j.1600-6143.2008.02301.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
Thymus transplantation shows promise for the treatment of athymia in complete DiGeorge anomaly. This report reviews the effects of dose of thymus tissue, ABO compatibility, HLA matching, culture conditions, age of donor and immunosuppression of recipient on immune outcomes at 1 year after transplantation. Forty-nine athymic subjects have been treated with cultured postnatal allogeneic thymus tissue; 36 (73%) survive with only one subject on immunosuppression at 1.5 years. Of 31 surviving subjects more than 1 year after transplantation, 30 (97%) developed naive T cells, T-cell proliferative responses to mitogens and a diverse T-cell receptor beta variable (TCRBV) repertoire. The dose of thymus tissue, HLA matching and use of immunosuppression had nonsignificant effects on these outcome variables. Removal of deoxyguanosine from culture medium and length of culture did not adversely affect outcomes. Use of thymus tissue from donors over 1 month of age, versus under 1 month, resulted in higher total T-cell numbers (p = 0.03). However, this finding must be confirmed in a prospective trial. Although subtle immune effects may yet be associated with some of the factors tested, it is remarkable that consistently good immune outcomes result despite variation in dose, HLA matching and use of immunosuppression.
引用
收藏
页码:1729 / 1736
页数:8
相关论文
共 23 条
[1]  
BARRETT DJ, 1981, J CLIN LAB IMMUNOL, V6, P1
[2]   PREDICTION OF PERSISTENT IMMUNODEFICIENCY IN THE DIGEORGE ANOMALY [J].
BASTIAN, J ;
LAW, S ;
VOGLER, L ;
LAWTON, A ;
HERROD, H ;
ANDERSON, S ;
HOROWITZ, S ;
HONG, R .
JOURNAL OF PEDIATRICS, 1989, 115 (03) :391-396
[3]   INEFFICIENT POSITIVE SELECTION OF T-CELLS DIRECTED BY HEMATOPOIETIC-CELLS [J].
BIX, M ;
RAULET, D .
NATURE, 1992, 359 (6393) :330-333
[4]   Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells [J].
Choi, EY ;
Jung, KC ;
Park, HJ ;
Chung, DH ;
Song, JS ;
Yang, SD ;
Simpson, E ;
Park, SH .
IMMUNITY, 2005, 23 (04) :387-396
[5]   SPECTRUM OF THE DIGEORGE SYNDROME [J].
CONLEY, ME ;
BECKWITH, JB ;
MANCER, JFK ;
TENCKHOFF, L .
JOURNAL OF PEDIATRICS, 1979, 94 (06) :883-890
[6]   The DiGeorge anomaly [J].
Hong, R .
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY, 2001, 20 (01) :43-60
[7]   Organ culture for thymus transplantation [J].
Hong, R ;
Moore, AL .
TRANSPLANTATION, 1996, 61 (03) :444-448
[8]   FIBROBLASTS CAN INDUCE THYMOCYTE POSITIVE SELECTION IN-VIVO [J].
HUGO, P ;
KAPPLER, JW ;
MCCORMACK, JE ;
MARRACK, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (21) :10335-10339
[9]   Statistical analysis of antigen receptor spectratype data [J].
Kepler, TB ;
He, M ;
Tomfohr, JK ;
Devlin, BH ;
Sarzotti, M ;
Markert, ML .
BIOINFORMATICS, 2005, 21 (16) :3394-3400
[10]   An alternate pathway for CD4 T cell development: Thymocyte-expressed MHC class II selects a distinct T cell population [J].
Li, W ;
Kim, MG ;
Gourley, TS ;
McCarthy, BP ;
Sant'Angelo, DB ;
Chang, CH .
IMMUNITY, 2005, 23 (04) :375-386