Presence of Donor-Derived DNA and Cells in the Urine of Sex-Mismatched Hematopoietic Stem Cell Transplant Recipients: Implication for the Transrenal Hypothesis

被引:25
作者
Hung, Emily C. W. [1 ,2 ]
Shing, Tristan K. F. [1 ]
Chim, Stephen S. C. [3 ]
Yeung, Philip C. [1 ]
Chan, Rebecca W. Y. [4 ]
Chik, Ki W. [5 ]
Lee, Vincent [5 ]
Tsui, Nancy B. Y. [1 ,2 ]
Li, Chi-Kong [5 ]
Wong, Cesar S. C. [6 ]
Chiu, Rossa W. K. [1 ,2 ]
Lo, Y. M. Dennis [1 ,2 ]
机构
[1] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Chem Pathol, Shatin, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Prince Wales Hosp, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Obstet & Gynaecol, Shatin, Hong Kong, Peoples R China
[4] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Accid & Emergency, Shatin, Hong Kong, Peoples R China
[5] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Paediat, Shatin, Hong Kong, Peoples R China
[6] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Clin Oncol, Shatin, Hong Kong, Peoples R China
关键词
BONE-MARROW-TRANSPLANTATION; GLOMERULAR MESANGIAL CELLS; FREE FETAL DNA; PRENATAL-DIAGNOSIS; MATERNAL PLASMA; COLORECTAL-CANCER; Y-CHROMOSOME; CHIMERISM; REGENERATION; CONTRIBUTE;
D O I
10.1373/clinchem.2008.113530
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
BACKGROUND: The term "transrenal DNA" was coined in 2000 to signify that DNA in urine may come from the passage of plasma DNA through the kidney barrier. Although DNA in the urine has the potential to provide a completely noninvasive source of nucleic acids for molecular diagnosis, its existence remains controversial. METHODS: We obtained blood and urine samples from 22 hematopoietic stem cell transplant (HSCT) recipients and used fluorescence in situ hybridization, PCR for short tandem repeats, mass spectrometry, quantitative PCR, and immunofluorescence detection to study donor-derived DNA in the urine. RESULTS: All HSCT recipients exhibited high amounts of donor-derived DNA in buffy coat and plasma samples. Male donor-derived DNA was detected in supernatants of urine samples from all 5 female sex-mismatched HSCT recipients. Surprisingly, the amount of DNA in urine supernatants was not correlated with the plasma value. Moreover, cell-free urine supernatants contained DNA fragments >350 bp that were absent in plasma. 'Donor-derived polymorphs were detected in urine by fluorescence in situ hybridization. Coincidentally, donor-derived cytokeratin-producing epithelial cells were discovered in urine samples from 3 of 10 sex-mismatched HSCT recipients as long as 14.2 years after transplantation. CONCLUSIONS: This report is the first to demonstrate the presence of donor-derived DNA in the urine of HSCT recipients; however, we show that much of this DNA originates from donor-derived cells, rather than from the transrenal passage of cell-free plasma DNA. Our discovery of donor-derived cytokeratin-producing epithelial cells raises interesting biological and therapeutic implications, e.g., the capacity of marrow stem cells to serve as an extrarenal source for renal tubule regeneration. (C) 2009 American Association for Clinical Chemistry
引用
收藏
页码:715 / 722
页数:8
相关论文
共 31 条
[1]   Detection of Y chromosome-specific DNA in the plasma and urine of pregnant women using nested polymerase chain reaction [J].
Al-Yatama, MK ;
Mustafa, AS ;
Ali, S ;
Abraham, S ;
Khan, Z ;
Khaja, N .
PRENATAL DIAGNOSIS, 2001, 21 (05) :399-402
[2]   Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: Recommendations from a Workshop at the 2001 Tandem Meetings [J].
Antin, JH ;
Childs, R ;
Filipovich, AH ;
Giralt, S ;
Mackinnon, S ;
Spitzer, T ;
Weisdorf, D .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2001, 7 (09) :473-485
[3]  
Botezatu I, 2000, CLIN CHEM, V46, P1078
[4]   Isolation and comparative study of cell-free nucleic acids from human urine [J].
Bryzgunova, Olga E. ;
Skvortsova, Tatyana E. ;
Kolesnikova, Elena V. ;
Starikov, Andrey V. ;
Rykova, Elena Yu. ;
Vlassov, Valentin V. ;
Laktionov, Pavel P. .
CIRCULATING NUCLEIC ACIDS IN PLASMA AND SERUM IV, 2006, 1075 :334-340
[5]   Size distributions of maternal and fetal DNA in maternal plasma [J].
Chan, KCA ;
Zhang, J ;
Hui, ABY ;
Wong, N ;
Lau, TK ;
Leung, TN ;
Lo, KW ;
Huang, DWS ;
Lo, YMD .
CLINICAL CHEMISTRY, 2004, 50 (01) :88-92
[6]  
Chiu RWK, 2001, CLIN CHEM, V47, P1607
[7]  
Cornacchia F, 2001, J CLIN INVEST, V108, P1649
[8]   Bone marrow transplantation can attenuate the progression of mesangial sclerosis [J].
Guo, Jian-Kan ;
Schedl, Andreas ;
Krause, Diane S. .
STEM CELLS, 2006, 24 (02) :406-415
[9]  
Gupta S, 2002, KIDNEY INT, V62, P1285, DOI 10.1046/j.1523-1755.2002.00569.x
[10]   Detection of cell-free fetal DNA in maternal urine [J].
Illanes, S. ;
Denbow, M. L. ;
Smith, R. P. ;
Overton, T. G. ;
Soothill, P. W. ;
Finning, K. .
PRENATAL DIAGNOSIS, 2006, 26 (13) :1216-1218