Başkent Üniversitesi Makaleler

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    Leflunomide Derivative FK778 Inhibits Production of Antibodies in an Experimental Model of Alloreactive T-B Cell Interaction
    (Başkent Üniversitesi, 2009-12) Ramos-Barrón, M. Angeles; Arias, Manuel; Merino, Ramón; Merino, Jesus; Gimenez, Teresa; Benito, Adalberto; Cosme, Lorena San; Agüeros, Consuelo; Santiuste, Ines; Gómez-Alamillo, Carlos
    Objectives: The contribution of humoral immune response in allograft and xenograft rejection has been clearly demonstrated in recent years. For this reason, inhibition of alloantibody production has become essential in managing transplanted patients. Here, we assessed the effects of the leflunomide derivative FK778 (FK778) in the control of antibody production resulting from semi­allogeneic cognate T-B–cell interactions. Materials and Methods: BALB/c mice were tolerized at birth with semiallogeneic spleen cells from (BALB/c × C57BL/6) F1 mice, with or without overexpression of human bcl-2 transgene in B cells. These tolerized mice were treated with different dosages of FK778, either from birth, or from the third week of age, when autoantibody production was detected. The production of autoantibodies, used as markers of semiallogeneic cognate T-B–cell interactions, was evaluated at different time points during drug administration or after the interruption of treatment. Results: FK778 treatment started at birth inhibited the production of semiallogeneic-driven antibodies in a dose-dependent manner. In addition, FK778 also reduced the levels of preformed circulating autoantibodies in adult mice, although the dosage required was 4 times higher than that used in neonates. However, the levels of IgG antibodies in these tolerized mice increased after FK778 withdrawal, indicating that FK778 failed to induce tolerance to semiallogeneic host CD4+ Th2 and/or donor B cells. Conclusions: Our results demonstrate the efficacy of FK778 in the control of antibody production resulting from semiallogeneic cognate T-B–cell interactions.
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    Plasmapheresis in the Treatment of Early Acute Kidney Allograft Dysfunction
    (Başkent Üniversitesi, 2006-12) Nafar, Mohsen; Farrokhi, Farhat; Hemati, Keyvan; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Einollahi, Behzad
    Objective: To evaluate the efficacy of plasmapheresis (PP) in kidney transplant recipients with acute humoral rejection (AHR). Patients and Methods: A retrospective review was conducted of all kidney allograft recipients who had undergone PP rescue therapy for early acute allograft dysfunction diagnosed as AHR at Shaheed Labbafinejad Medical Center from 1995 to 2002. Results: Twelve patients (4 men and 8 women; median age, 32 years; age range, 15-68 years) with AHR were treated with PP. The median time from transplantation to AHR was 6 days (range, 2-7 days). PP was performed in 2 to 11 sessions (median, 8.5 sessions) in the patients studied. Eight patients responded to that treatment, and their creatinine value normalized. Those responders were monitored for a median of 162.5 weeks (range, 69.3-484.7 weeks), and all had a functioning allograft during the follow-up period except for 1 patient in whom the graft failed 154 weeks after transplantation. In the 4 remaining patients (nonresponders), the allograft failed within the first posttransplant month. The median time from the acute serum creatinine elevation to the initiation of PP was 6 days in responders and 18.6 days in nonresponders (P = .37). Conclusions: We suggest that PP with or without other therapeutic measures may have a role in the salvage of grafts with early acute dysfunction that is resistant to conventional therapy. Our findings indicate that graft survival in patients with AHR who respond to PP can be comparable to that in other kidney recipients.