scholarly journals First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques

2020 ◽  
Vol 9 (11) ◽  
pp. 3694
Author(s):  
Iori Kisu ◽  
Yojiro Kato ◽  
Yohei Masugi ◽  
Hirohito Ishigaki ◽  
Yohei Yamada ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Antithymocyte Globulin ◽  
Nonhuman Primates ◽  
Humoral Rejection ◽  
Term Survival ◽  
Uterus Transplantation ◽  
Histocompatibility Complex ◽  
Cynomolgus Macaques ◽  
Donor Specific Antibodies

Delivery following uterus transplantation (UTx)—an approach for treating uterine factor infertility—has not been reported in nonhuman primate models. Here, six female major histocompatibility complex (MHC)-defined cynomolgus macaques that underwent allogeneic UTx were evaluated. Antithymocyte globulin and rituximab were administered to induce immunosuppression and a triple maintenance regimen was used. Menstruation resumed in all animals with long-term survival, except one, which was euthanized due to infusion associated adverse reaction to antithymocyte globulin. Donor-specific antibodies (DSA) were detected in cases 2, 4, and 5, while humoral rejection occurred in cases 4 and 5. Post-transplant lymphoproliferative disorder (PTLD) developed in cases 2 and 3. Pregnancy was attempted in cases 1, 2, and 3 but was achieved only in case 2, which had haploidentical donor and recipient MHCs. Pregnancy was achieved in case 2 after recovery from graft rejection coincident with DSA and PTLD. A cesarean section was performed at full-term. This is the first report of a successful livebirth following allogeneic UTx in nonhuman primates, although the delivery was achieved via UTx between a pair carrying haploidentical MHCs. Experimental data from nonhuman primates may provide important scientific knowledge needed to resolve unsolved clinical issues in UTx.

scholarly journals Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques

2019 ◽  
Vol 8 (10) ◽  
pp. 1572 ◽  
Author(s):  
Kisu ◽  
Ishigaki ◽  
Emoto ◽  
Kato ◽  
Yamada ◽  
...  
Keyword(s):  
Cynomolgus Macaque ◽  
Uterine Blood Flow ◽  
Long Term Outcomes ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Uterus Transplantation ◽  
Cynomolgus Macaques ◽  
Donor Specific Antibodies ◽  
Experimental Stage

Uterus transplantation (UTx) is an option for women with uterine factor infertility to have a child, but is still in the experimental stage. Therefore, allogeneic animal models of UTx are required for resolution of clinical issues. In this study, long-term outcomes were evaluated in four recipients (cases 1–4) after allogeneic UTx in cynomolgus macaques. Immunosuppression with antithymocyte globulin induction and a triple maintenance regimen was used. Postoperative ultrasonography and biopsy of the transplanted uterus and immunoserological examinations were performed. All four recipients survived for >3 months after surgery, but continuous menstruation did not resume, although temporary menstruation occurred (cases 1 and 2). All animals were euthanized due to irreversible rejection and no uterine blood flow (cases 1, 2 and 4) and post-transplant lymphoproliferative disorder (case 3). Donor-specific antibodies against MHC class I and II were detected in cases 1, 2 and 4, but not in case 3. Peripheral lymphocyte counts tended to elevate for CD3+, CD20+ and NK cells in conjunction with uterine rejection, and all animals had elevated stimulation indexes of mixed lymphocyte reaction after surgery. Establishment of allogeneic UTx in cynomolgus macaque requires further exploration of immunosuppression, but the clinicopathological features of uterine rejection are useful for development of human UTx.

Anti–B-Cell Monoclonal Antibody Treatment of Severe Posttransplant B-Lymphoproliferative Disorder: Prognostic Factors and Long-Term Outcome

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3137-3147 ◽  
Author(s):  
Malika Benkerrou ◽  
Jean-Philippe Jais ◽  
Véronique Leblond ◽  
Anne Durandy ◽  
Laurent Sutton ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Lymphoproliferative Disorder ◽  
Long Term Results ◽  
Cytotoxic T Cell ◽  
Antibody Treatment ◽  
Term Survival ◽  
Long Term Outcome ◽  
Long Term Study

Abstract B-lymphoproliferative disorder (BLPD) is a rare but severe complication of organ and bone marrow transplantation (BMT). Profound cytotoxic T-cell deficiency is thought to allow the outgrowth of Epstein-Barr virus–transformed B cells. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure BLPD. Therapeutic approaches using chemotherapy or antiviral drugs have limited effects on survival. Adoptive immunotherapy with donor T-cell infusions has given promising results in BMT recipients. We previously reported that administration of two monoclonal anti–B-cell antibodies (anti-CD21 and anti-CD24) could contribute to the control of oligoclonal BLPD. Here we report the long-term results of treatment with these monoclonal anti–B-cell antibodies for cases of severe BLPD. In an open multicenter trial, 58 patients in whom aggressive B-cell lymphoproliferative disorder developed after BMT (n = 27) or organ (n = 31) transplantation received 0.2 mg/kg/d of specific anti-CD21 and anti-CD24 murine monoclonal antibodies (MoAbs) for 10 days. The treatment was well tolerated. Thirty-six of the 59 episodes of BLPD in the 58 patients presented complete remission (61%). The relapse rate was low (3 of 36, 8%). Multivariate analysis identified the following risk factors for partial or no response to anti–B-cell MoAb therapy: multivisceral disease (P ≤ .005), central nervous system involvement (P ≤ .05), and late onset of BLPD (P ≤ .005). The overall long-term survival was 46% (median follow-up, 61 months); it was lower among BMT patients (35%) than organ transplant patients (55%). None of the patients who had received BMT for hematological malignancy survived for 1 year. Eight of these 11 patients presented monoclonal BLPD. Tumor burden was the only other variable that contributed significantly to poor survival. Thus, as assessed from this long-term study, the use of anti–B-cell MoAbs therefore appears to be a safe and relatively effective therapy for severe posttransplant BLPD. © 1998 by The American Society of Hematology.

scholarly journals Antibody-Mediated Rejection and Sponge Effect in a Redo Lung Transplant Recipient

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Ashwini Arjuna ◽  
Michael T. Olson ◽  
Sofya Tokman ◽  
Rajat Walia ◽  
Thalachallour Mohanakumar ◽  
...  
Keyword(s):  
Transplant Recipient ◽  
Lung Transplant ◽  
Human Leukocyte ◽  
Lung Transplant Recipient ◽  
Term Survival ◽  
Antibody Mediated Rejection ◽  
Leukocyte Antigens ◽  
Allograft Failure ◽  
Donor Specific Antibodies

Long-term survival after lung transplant remains severely limited by chronic lung allograft dysfunction. Antibody-mediated rejection of lung transplant allografts is usually caused by donor-specific antibodies (DSAs) directed toward donor human leukocyte antigens (HLAs). Typically, patients with antibody-mediated rejection have significantly higher circulating DSAs and increased mean fluorescence intensity than those without antibody-mediated rejection. However, some patients with antibody-mediated rejection have low mean fluorescence intensities, partly due to the “sponge effect” related to DSAs binding to HLA molecules within the lung. Herein, we report the case of an 18-year-old, female lung transplant recipient who required retransplantation and developed circulating DSAs directed toward the first allograft but detected in circulation only after retransplantation. The present case draws attention to a rare finding of sponge effect in a patient with antibody-mediated rejection leading to allograft failure.

scholarly journals Colchicine allows prolonged survival of highly reactive renal allograft in the rat.

1993 ◽  
Vol 4 (6) ◽  
pp. 1294-1299
Author(s):  
D Ostermann ◽  
N Perico ◽  
O Imberti ◽  
C Barbui ◽  
M Bontempelli ◽  
...  
Keyword(s):  
Mixed Lymphocyte Culture ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocyte Culture ◽  
Brown Norway ◽  
Time Intervals ◽  
Term Survival ◽  
Kidney Allograft ◽  
Beneficial Effects ◽  
Histocompatibility Complex

Colchicine, with its immunosuppressive properties, has been used with beneficial effects in autoimmune diseases. Whether colchicine, by virtue of the above properties, could attenuate the process of kidney allograft rejection in the rat is investigated in this report. Untreated Lewis rats (N = 6) given an incompatible kidney allograft from Brown-Norway rats rejected the graft within 12 days. Colchicine at a daily ip dose of 40 (N = 6) or 10 (N = 4) micrograms/kg promoted long-term survival (> 170 days) of major histocompatibility complex-incompatible kidney grafts. Animals (N = 4) given 4 micrograms of colchicine per kilogram had a graft failure within 10 days. Experiments have also been performed to evaluate the effect of colchicine withdrawal at different time intervals from transplantation on subsequent allograft survival. Colchicine (40 micrograms/kg per day ip) was given for 12, 6, or 1 mo or for 15 days to an additional four groups of six animals each without any other immunosuppressants. The withdrawal of colchicine did confer long-term inhibition of the immune system in animals treated for at least 1 mo, as documented by a graft survival of more than 80 days. By contrast, those animals who discontinued colchicine after only 15 days of treatment had graft rejection within the next 8 days. Mixed lymphocyte culture experiments showed a significant (P < 0.01) reduction of the proliferation of peripheral blood lymphocytes taken from all groups of animals 30 days after colchicine withdrawal when challenged with Brown-Norway lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

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