A clinical research consortium sponsored by NIAID and JDRF
Newell KA, Asare A, Gisler T, Turka L, Seyfert-Margolis V, Suthanthiran MS, Burlingham W, Marks W
Introduction. Decisions about the minimization and ultimate withdrawal of immunosuppression (IS) would be facilitated by the identification of biomarkers associated with operational tolerance (OT).
Methods. Tolerant kidney transplant recipients (off all IS for > 1yr with stable function, N=22) were compared to recipients with stable function on IS (SIS N=34), recipients with CAN (N=20), and healthy volunteers (HV, N=18). PBMC, whole blood total RNA, and urine samples from each group were examined using flow cytometry, microarrays, and RT-PCR respectively.
Results. Analysis of microarrays revealed significantly higher expression of B cell differentiation genes in tolerant recipients compared to the SIS and CAN groups. Consistent with this finding, tolerant recipients also displayed higher numbers of naïve B cells in peripheral blood and increased expression of CD20 in urine relative to the SIS and CAN groups. No differences in Treg or genes associated with regulatory cells were observed in tolerant recipients. These analyses failed to demonstrate significant differences between tolerant recipients and HVs although support vector machine learning methods suggested potential differences in a number of genes including NFAT and calcineurin. Finally, relative to tolerant patients, those with CAN showed decreased numbers of T and NK cells and expressed lower levels of genes associated with immune cell activation in peripheral blood.
Conclusions. Differences in B cell numbers may be useful in identifying tolerant renal transplant recipients or those predisposed to developing tolerance and could potentially provide insights into the mechanisms of tolerance.
