Peripheral blood microchimerism in human liver and renal transplant recipients: rejection despite donor-specific chimerism.
BACKGROUND
Development of donor-specific microchimerism (DSM) has been proposed as one of the possible mechanisms for induction and maintenance of allograft tolerance. The aim of this study was to determine: (1) the state of DSM in liver transplant (LTx) and renal transplant (RTx) recipients, (2) whether the persistent presence of an allograft is a requirement for maintenance of chimerism, and (3) whether donor-specific blood transfusions (DST) facilitate chimerism development in RTx recipients and whether this correlates with allograft function.


METHODS
Qualitative and quantitative analysis of DSM in peripheral blood of LTx and RTx recipients was assessed by polymerase chain reaction and competitive polymerase chain reaction using HLA-DR probes for mismatched antigens between the donor and recipient.


RESULTS
LTx recipients (11 of 12) who had or were having rejection were positive for DSM in circulation compared with 4 of 11 with normal allograft function (P<0.01). The number of donor cells did not correlate with allograft function. LTx recipients (4 of 4) who lost their first allograft and underwent retransplantation retained DSM for the first donors. RTx recipients who received DST (8 of 8) were positive for DSM compared with 6 of 12 of nontransfused recipients (P<0.045).


CONCLUSIONS
The results suggest that LTx and RTx recipients undergo rejection despite DSM. The development of DSM may not be a prerequisite for normal allograft function. Once DSM is established, the presence of the allograft is not required for maintenance of chimerism. DST facilitated the development of DSM in RTx recipients. Direct correlation was not observed between the development of DSM and allograft function in either DST or nontransfused RTx recipients.
Sivasai
K S
KS
Department of Surgery, Washington University of Medicine, St. Louis, Missouri 63110, USA.
Alevy
Y G
YG
Duffy
B F
BF
Brennan
D C
DC
Singer
G G
GG
Shenoy
S
S
Lowell
J A
JA
Howard
T
T
Mohanakumar
T
T
D000483:Alleles; D001803:Blood Transfusion; D015139:Blotting, Southern; D016026:Bone Marrow Transplantation / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000473:pathology; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D016133:Polymerase Chain Reaction; D012086:Reoperation; D018183:Transplantation Chimera / Q000502:physiology; D014184:Transplantation, Homologous / Q000502:physiology
D006684:HLA-DR Antigens