The biological significance of donor-specific microchimerism (DSM) in solid organ transplantation is unresolved. It has been reported both as a favourable feature, which may facilitate induction and maintenance of tolerance, and as a sign of graft-vs-host disease. Here, we applied a quantitative real-time PCR assay (qRT-PCR) to a selected series of kidney transplant recipients to measure the level of microchimerism in relation to allograft function and survival. DSM level was assessed by scoring the HLA-DRB1 locus in 54 patients (42 males, 12 females) with more than 2 years of follow-up after transplantation; 38 patients were considered to have stable renal function (SRF) and 16 had allograft dysfunction (AD). Among patients with AD, 12 (75%) showed detectable level of microchimerism, compared to 11(29%) SRF patients (Odds Ratio 736, 95% Cl 1.7-35.2; p<0.01). In addition, AD patients showed a higher mean donor genome equivalents (6.5x10(-5) vs. 2.4x10(-5): p<0.001). SRF patients were re-evaluated two years later; 2 out of 27 DSM negative vs. 2 out of 11 DSM positive had lost their transplanted organ. In conclusion, qRT-PCR applied to peripheral blood shows significant association between DSM and allograft dysfunction in kidney transplant patients. (C) 2011 Elsevier B.V. All rights reserved.

Association of donor-specific microchimerism with graft dysfunction in kidney transplant patients

VISTOLI, FABIO;
2012-01-01

Abstract

The biological significance of donor-specific microchimerism (DSM) in solid organ transplantation is unresolved. It has been reported both as a favourable feature, which may facilitate induction and maintenance of tolerance, and as a sign of graft-vs-host disease. Here, we applied a quantitative real-time PCR assay (qRT-PCR) to a selected series of kidney transplant recipients to measure the level of microchimerism in relation to allograft function and survival. DSM level was assessed by scoring the HLA-DRB1 locus in 54 patients (42 males, 12 females) with more than 2 years of follow-up after transplantation; 38 patients were considered to have stable renal function (SRF) and 16 had allograft dysfunction (AD). Among patients with AD, 12 (75%) showed detectable level of microchimerism, compared to 11(29%) SRF patients (Odds Ratio 736, 95% Cl 1.7-35.2; p<0.01). In addition, AD patients showed a higher mean donor genome equivalents (6.5x10(-5) vs. 2.4x10(-5): p<0.001). SRF patients were re-evaluated two years later; 2 out of 27 DSM negative vs. 2 out of 11 DSM positive had lost their transplanted organ. In conclusion, qRT-PCR applied to peripheral blood shows significant association between DSM and allograft dysfunction in kidney transplant patients. (C) 2011 Elsevier B.V. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11697/221584
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