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Farris A.B.,Massachusetts General Hospital | Farris A.B.,Emory University | Farris A.B.,Harvard University | Taheri D.,Massachusetts General Hospital | And 28 more authors.
American Journal of Transplantation | Year: 2011

An idiopathic capillary leak syndrome ('engraftment syndrome') often occurs in recipients of hematopoietic cells, manifested clinically by transient azotemia and sometimes fever and fluid retention. Here, we report the renal pathology in 10 recipients of combined bone marrow and kidney allografts. Nine developed graft dysfunction on day 10-16 and renal biopsies showed marked acute tubular injury, with interstitial edema, hemorrhage and capillary congestion, with little or no interstitial infiltrate (≤10%) and marked glomerular and peritubular capillary (PTC) endothelial injury and loss by electron microscopy. Two had transient arterial endothelial inflammation; and 2 had C4d deposition. The cells in capillaries were primarily CD68; mononuclear cells and CD3; T cells, the latter with a high proliferative index (Ki67). B cells (CD20) and CD4 T cells were not detectable, and NK cells were rare. XY FISH showed that CD45 cells in PTCs were of recipient origin. Optimal treatment remains to be defined; two recovered without additional therapy, six were treated with anti-rejection regimens. Except for one patient, who later developed thrombotic microangiopathy and one with acute humoral rejection, all fully recovered within 2-4 weeks. Graft endothelium is the primary target of this process, attributable to as yet obscure mechanisms, arising during leukocyte recovery. © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.


Levesque V.,Transplantation Biology Research Center | Bardwell P.D.,Transplantation Biology Research Center | Shimizu I.,Transplantation Biology Research Center | Haspot F.,Transplantation Biology Research Center | And 3 more authors.
American Journal of Transplantation | Year: 2011

Presensitization to HLA antigens limits the success of organ transplantation. The achievement of donorspecific tolerance via mixed chimerism could improve outcomes of transplantation in presensitized patients. In presensitized B-cell-deficient lMT B6 mice, we developed nonmyeloablative bone marrow transplantation (BMT) regimens that successfully tolerized presensitized T cells, achieving long-term(LT) multilineage chimerism and tolerance to donor-type skin. To apply these regimens in wild-type (WT) animals while avoiding antibody-mediated destruction of donor bone marrow cells, presensitized WT B6 mice were rested >2 years to allow alloantibody clearance. However, chimerism and tolerance were not reliably achieved in LT presensitized WT B6 mice in which alloantibody had declined to minimal or undetectable levels before BMT. Strong antidonor memory T-cell responses were detected in LT presensitizedWT B6mice after rejection of donor bone marrow (BM) occurred, whereas levels of alloantibody remained consistently low. In contrast, presensitized lMT B6 mice had diminished memory Tcell responses compared to WT B6 mice. These data implicate T-cell memory, but not alloantibody, in rejection of donor BM in LT presensitized WT mice. © Copyright 2011 The American Society of Transplantation.

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