Saturday, June 25, 2016

Acquired down-regulation of donor-specific antibody production after ABO-incompatible kidney transplantation

The mechanism of long-term B cell immunity against donor blood group antigens in recipients who undergo ABO-incompatible (ABOi) living-donor kidney transplantation (LKTx) is unknown. To address this question, we evaluated serial anti-A and anti-B antibody titers in 50 adult recipients. Donor-specific antibody titers remained low (≤1:4) in 42 recipients (84%). However, antibodies against nondonor blood group antigens were continuously produced in recipients with blood type O. We stimulated recipients’ peripheral blood mononuclear cells in vitro to investigate whether B-cells produced antibodies against donor blood group antigens in the absence of graft adsorption in vivo. Antibodies in cell culture supernatant were measured using specific enzyme-linked immunosorbent assays (ELISA). Thirty-five healthy volunteers and 57 recipients who underwent ABO-compatible LKTx served as controls. Antibody production in vitro against donor blood group antigens by cells from ABOi LKTx patients was lower than in the control groups. Immunoglobulin deposits were undetectable in biopsies of grafts of eight recipients with low antibody titers (≤1:4) after ABOi LKTx. One patient with blood type A1 who received a second ABOi LKTx from a type B donor did not produce B-specific antibodies. These findings suggest diminished donor-specific antibody-production function in the setting of adult ABOi LKTx (read more)

Saturday, June 4, 2016

Pretransplantation donor-recipient pair seroreactivity against BK polyomavirus predicts viremia and nephropathy after kidney transplantation

Kidney transplant donors are currently not implicated in predicting BK polyomavirus (BKPyV) infection in kidney transplant recipients. It has been postulated, however, that BKPyV infection originates from the kidney allograft. Since BKPyV-seroreactivity correlates with BKPyV-replication and, therefore, might mirror the infectious load, we investigated whether BKPyV-seroreactivity of the donor predicts viremia and BKPyV-associated nephropathy (BKPyVAN) in the recipient. In a retrospective cohort of 407 living kidney donor-recipient pairs pretransplantation donor and recipient sera were tested for BKPyV IgG-levels and correlated with the occurrence of recipient BKPyV viremia and BKPyVAN within one year posttransplantation. As such, donor BKPyV IgG-level was strongly associated with BKPyV viremia and BKPyVAN (p < 0.001), while recipient BKPyV-seroreactivity showed a non-significant inverse trend. Pairing of high BKPyV-seroreactive donors with low seroreactive recipients resulted in a 10-fold increased risk for BKPyV viremia (HR 10.1, 95% CI: 3.5 – 29.0, p < 0.001). In multivariate analysis, donor BKPyV-seroreactivity was the strongest pretransplantation factor associated with viremia (p < 0.001) and BKPyVAN (p = 0.007). The proportional relation between donor BKPyV-seroreactivity and recipient infection suggests that donor BKPyV-seroreactivity reflects the infectious load of the kidney allograft, and calls for the use of pretransplantation BKPyV-serological testing of (potential) donors and recipients (read more)