title: Donor-derived peripheral mononuclear cell DNA is associated with stable kidney allograft function: a randomized controlled trial.
abstract: A large body of literature has documented an inconsistent relationship of peripheral donor cell chimerism with alloimmune tolerance following kidney transplantation. We revisit this association with assays capable of quantifying cellular microchimerism with 150-1500-fold greater sensitivity than previously utilized allo-antibody based flow cytometric approaches. Forty renal transplant patients, 20 with concurrent donor bone marrow infusion (DBMI) and 20 control participants without infusion were prospectively monitored for peripheral blood microchimerism using donor polymorphism-specific quantitative real-time PCR. Thirty-eight patients were evaluated for microchimerism, 19 in each group. The frequency of testing positive for (95% vs. 58%, p = 0.02) and mean concentrations of microchimerism (115 ± 66 vs. 13 ± 3 donor genomes/million recipient genomes, p = 0.007), respectively, were higher in infused patients compared with controls. Thirty-one patients maintained stable graft function; 17 in the DBMI group vs. 14 in controls. Patients with stable graft function in the DBMI group compared with control patients harbored microchimerism more frequently (94 vs. 50%, p = 0.01) and at higher concentrations (123 ± 67 vs. 11 ± 4, p = 0.007), respectively. Significant correlation between dose of infused cells and microchimerism levels was found post-transplant (p = 0.01). Using very sensitive assays, our findings demonstrate associations between the presence and quantity of microchimerism with stable graft function in infused patients.
authors.affiliation: Immunology Department, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Ghasem
authors.initials: G
authors.lastname: Solgi
authors.forename: Joannis
authors.initials: J
authors.lastname: Mytilineos
authors.forename: Vijayakrishna
authors.initials: V
authors.lastname: Gadi
authors.forename: Biswajit
authors.initials: B
authors.lastname: Paul
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Pourmand
authors.forename: Abdolrasoul
authors.initials: A
authors.lastname: Mehrsai
authors.forename: Behrouz
authors.initials: B
authors.lastname: Nikbin
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Amirzargar
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D046528:Chimerism; D004247:DNA / Q000378:metabolism*; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D004247:DNA