Early hematopoietic microchimerism predicts clinical outcome after kidney transplantation.
BACKGROUND
The presence of a few circulating donor cells in recipient's blood was first thought to be only an epiphenomenon of solid organ transplantation, also called microchimerism, but several authors have suggested that these circulating cells may contribute to tolerance induction. This study aims to assess the rate of microchimerism after kidney transplantation and determine its influence on acute rejection in a 4-year follow-up.


METHODS
A total of 84 single-kidney recipients were included for microchimerism detection and quantification 2, 6, 12, and 18 months after transplantation by specific detection of non-shared STR, VNTR, human leukocyte antigen-A, -B, -DRB1, and SRY alleles. Kinetic establishment of microchimerism was monitored in a double kidney transplanted recipient for 150 min after declamping and after 7 days.


RESULTS
Microchimerism was detected in 56.2% of kidney recipients 2 months after transplantation (M2): this fell to 30.1% at 12 months. In renal calcineurin inhibitor-based immunosuppression cohort (n=73), the microchimerism-negative group (n=32) showed 37.9% biopsy-proven acute rejection (BPAR), whereas in the microchimerism-positive group (n=41), no recipient did (P<0.001). Regardless of immunosuppression, BPAR incidence was 35.6% and 4.9%, respectively (P<0.001). Multivariate study showed microchimerism as a protective factor against BPAR (odds ratio: 8.3; 95% confidence interval: 1.8 to 37.9; P = 0.006), blinding other well-known rejection-risk variables. Microchimerism M2 presence did not correlate with a multifactorial critical outcome such as late graft loss.


CONCLUSIONS
Microchimerism was frequent after kidney transplantation and correlated with a significantly lower incidence of rejection. We propose that early microchimerism monitoring could help early detection of low rejection-risk recipients.
Pujal
Josep-Maria
JM
Alloreactivity Unit, Translational Research Laboratory, Institut Català d'Oncologia, Hospital Duran i Reynals, Barcelona, Spain. jmpujal@idibell.org
Grinyó
Josep M
JM
Gil-Vernet
Salvador
S
Caldes
Anna
A
Hernández
Pilar
P
Mestre
Mariona
M
Encuentra
Maite
M
Perez-Garcia
Arianne
A
Gallardo
David
D
D005500:Follow-Up Studies; D006680:HLA Antigens / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D007700:Kinetics; D016133:Polymerase Chain Reaction; D013997:Time Factors; D018183:Transplantation Chimera; D017211:Treatment Failure; D016896:Treatment Outcome
D006680:HLA Antigens