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Pregnancy After Liver and Other Transplantation
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Belatacept is an immunosuppressant agent that works as a selective T-cell co-stimulator blocker. It was approved for use in kidney transplant recipients in 2011. The Food and Drug Administration (FDA) has not approved its use during pregnancy [50]; however, case reports of uncomplicated pregnancies in KTx recipients have been published since it was first used in two pregnant patients in 2018 [51]. Again in 2020, a successful pregnancy was reported in a woman with two previous LTx in the setting of belatacept use [52].
Future therapies in lung transplantation
Published in Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell, LUNG Transplantation, 2016
Elizabeth A. Lendermon, John F. McDyer
To effectively block interaction of CD28 and B7 without consequent agonistic effects, the extracellular portion of CTLA4 was fused to a mutated Fc portion of human IgG1 to create CTLA4Ig (abatacept [Orencia]). Because CTLA4 binds to B7 with higher avidity and affinity than to CD28, CTLA4Ig competes with CD28 for binding. CTLA4Ig alone or in combination with other stimulation blockade has been shown in several experimental rodent transplant models to result in improved allograft acceptance.3–9 Notably, CTLA4Ig in combination with anti-CD154 has been demonstrated to improve lung allograft acceptance in mouse orthotopic lung transplantation.10 However, in at least some models, donor-specific transfusion appears to be required for durable tolerance.11 Abatacept was approved for use in patients with rheumatoid arthritis in 2006. Because abatacept unfortunately did not effectively improve allograft acceptance in nonhuman primate renal transplant recipients, the second-generation drug belatacept, which demonstrates improved affinity for B7, was developed. Belatacept was approved for use in renal transplantation in 2011, and it has shown some favorable effects in clinical studies of renal transplant patients.
Immunosuppressive therapy post-transplantation in children: what the clinician needs to know
Published in Expert Review of Clinical Immunology, 2020
Newer drugs such as belatacept have not been systematically studied in the pediatric transplant patient population. Since the approval of belatacept in 2011 for use in de novo adult kidney transplantation, this CD80/86 – CD28 co-stimulation blocker has been shown to be a valuable treatment option for maintenance immunosuppression [98]. Belatacept in adults has been associated with superior glomerular filtration rate as compared to calcineurin inhibitor-based treatments because of the absence of nephrotoxicity. Additionally, belatacept avoids the cardiovascular side effects (e.g. hypertension and dyslipidemia) caused by a calcineurin inhibitor-based-regimen [98]. Clearly, much additional work is needed to define optimal immunosuppressive regimens in pediatric renal transplant patients, particularly with respect to newer and evolving regimens. The safety and efficacy of these protocols with special emphasis on long-term graft survival and PTLD need to be established.
Belatacept in kidney transplantation and its limitations
Published in Expert Review of Clinical Immunology, 2019
Johan Noble, Thomas Jouve, Bénédicte Janbon, Lionel Rostaing, Paolo Malvezzi
In 2019, the cornerstone of immunosuppression after kidney transplantation still relies on calcineurin inhibitors (CNIs: cyclosporine A or tacrolimus). However, these drugs are known to be nephrotoxic and can cause acute and/or chronic toxicity on the kidney graft [1,2], and also contribute to new-onset diabetes (NODAT) [3] and hypertension [4]. This nephrotoxicity is supported by clinical and animal studies. Although the link between CNI and chronic graft failure is still controversial, it has led clinicians to seek new immunosuppressive regimens that avoid calcineurin inhibitors [5]. Although CNIs act on the first signal, inhibition of the second signal, or the co-stimulation signal, is a promising approach. Several proteins are involved in the co-stimulation of effector T-cells. To date, the more clinically relevant co-stimulation pathway that is targeted after organ transplantation is the interaction between the clusters of differentiation (CD) between CD28 and CD80 (B7–1)/86 (B7–2) [6,7]. The single agent interfering with this co-stimulation pathway and currently used in clinical transplantation is belatacept, which targets CD80/CD86 antigens. However, targeting CD28 via a monoclonal antibody is still in its infancy. In this review we examine the use of belatacept in kidney transplantation and address its clinical limitations.
Intravenous immunoglobulins modify relapsing membranous glomerulonephritis after kidney transplantation: a case report
Published in Acta Clinica Belgica, 2018
Sanne Steyaert, Jo Van Dorpe, Anne Hoorens, Wim Van Biesen, Steven Van Laecke
A complimentary role of the co-stimulatory blockade of belatacept, however, cannot be excluded. Belatacept is a human fusion protein combining a modified extra-cellular portion of CTLA-4 with the Fc fragment of human IgG1 and inhibits T cell activation 10 times stronger than abatacept [8]. There are some preliminary data concerning the therapeutic potential of abatacept, a co-stimulatory inhibitor that targets the podocytic B7-1 protein (CD80). Abatacept induced a total or partial remission in five patients with relapsing focal segmental glomerulosclerosis (FSGS) in the kidney graft and strong expression of the co-stimulatory molecule B7-1, thereby protecting from beta1-integrin activation, which leads to podocyte migration [9]. The role of the podocyte in glomerular diseases has already been well-established and is the primary target in the onset of IMGN, causing proteinuria secondary to foot process effacement [10]. Very strong staining of B7-1 can, as in FSGS, also be found on the podocytes of patients with IMGN but the clinical use of abatacept could not be validated afterward in FSGS or in other glomerulopathies [9]. The potential role of belatacept seems less likely since the relapse occurred under treatment with it.