A clinical research consortium sponsored by NIAID and JDRF
Porcheray F, Wong W, Saidman Sl, Girouard TC, Chittenden M, Shaffer J, Tolkoff-Rubin N, Dey BR, Spitzer TR, Colvin RB, Cosimi AB, Kawai T, Sachs DH, Sykes M, Zorn E, DeVito J
Massachusetts General Hospital, Boston, MA
Five patients with end-stage kidney disease received combined kidney and bone marrow transplants from HLA haploidentical donors following non-myeloablative conditioning to induce renal allograft tolerance. Immunosuppressive therapy was successfully discontinued in 4 patients with subsequent follow up of 3 to 6 years. This allograft acceptance was accompanied by specific T cell unresponsiveness to donor antigens. However, 2 of these 4 patients showed evidence of a de novo antibody response to the graft between one and two years after transplant. These humoral responses were characterized by the presence of donor ClassII-specific antibodies in the serum of these 2 patients and by C4d deposition in the graft of one patient, and are still ongoing while no functional graft impairment has been observed. Immunofluorescence staining, ELISA assays and antibody profiling using protein microarrays demonstrated the co-development of auto- and alloantibodies in these patients. These responses were preceded by elevated serum BAFF levels only for these 2 patients and coincided with B cell reconstitution as revealed by a high frequency of transitional B cells in the periphery.
