Prospective study of microchimerism in transplant recipients.
BACKGROUND
We evaluated peripheral blood microchimerism in 48 consecutive organ transplant recipients (35 kidneys, ten livers, one kidney-liver, one kidney-pancreatic islet, one kidney pancreas) up to 12 months post-transplantation. Patients were categorized according to the presence or absence of rejection episodes, and the patterns of microchimerism in the two groups were then compared.


METHODS
DNA was extracted from donor, pre-transplant, and post-transplant peripheral blood samples. Several polymerase chain reaction (PCR)-based assays were developed for the detection of microchimerism. Assay sensitivities ranged from 0.0001 to 3%.


RESULTS
Microchimerism was detected only in sex-mismatched cases (male donors and female recipients) using nested PCR for a Y-chromosome marker. There were ten such cases (six kidneys, two livers, and two combined organ transplants). In patients without rejection (n = 7), there was a peak of donor-DNA at 1-3 wk post-transplantation followed by a second peak between 3 wk and 4 months. In patients with biopsy-proven rejection (n = 3), the peaks were absent and the levels of microchimerism were extremely low (< 0.001%). Microchimerism levels declined in all 10 patients and were barely detectable 1 yr post-transplantation. Microchimerism was not detected in the remaining 38 patients despite using a battery of sensitive PCR-based assays.


CONCLUSIONS
In our study, microchimerism was detected using the Y-chromosome PCR assay only and the level of donor-DNA in a given patient varied over time. This study highlights the difficulties in establishing a correlation between microchimerism and transplant tolerance.
McDaniel
H B
HB
Department of Surgery, Indiana University Hospital, Indianapolis 46202-5250, USA.
Yang
M
M
Sidner
R A
RA
Jindal
R M
RM
Sahota
A
A
D000293:Adolescent; D000328:Adult; D001769:Blood; D004247:DNA / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology; D006085:Graft Survival; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000473:pathology; D016030:Kidney Transplantation / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000473:pathology; D011446:Prospective Studies; D012737:Sex Factors; D018183:Transplantation Chimera / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics
D004247:DNA