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Transplantation
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Jonathon Olsburgh, Rhana H. Zakri
Treatment for rejection is guided by features on transplant biopsy, such as:T-cell- or B-cell-mediated rejection.Evidence of donor-specific antibody (antibody-mediated rejection (AMR)).Involvement of graft vasculature (vascular rejection).
Intestinal Transplantation
Published in John K. DiBaise, Carol Rees Parrish, Jon S. Thompson, Short Bowel Syndrome Practical Approach to Management, 2017
Sherilyn Gordon Burroughs, Douglas G. Farmer
Regarding immune risks, the donor and recipient should be blood group identical/compatible to avoid hyperacute (a type of antibody-mediated) rejection. The significance of HLA-preformed antibodies is becoming increasingly evident. HLA antigen typing and donor-specific antibody (DSA) testing is now routinely performed at many centers. Although known to translate to an increased likelihood of early graft dysfunction in sensitized recipients, specifics regarding the interplay of elevated non-DSA and DSA titers and long-term graft function are less clear. Several studies demonstrate the negative impact of preformed antibody as well as the development of de novo antibody on clinical outcomes after ITx [40–42]. Contrary to prior experience with lengthy cross-match times (precluding practical utility in using the test for donor allocation due to prolongation of CIT), virtual cross-match techniques have the promise of offering expeditious results. As shown in a small cohort of ITx recipients [43], as more experience is gained with use of virtual cross-match for organ allocation, the long-term risks associated with the presence of specific titers of B- and T-cell alloantibodies can be better elucidated.
The humoral response to lung transplantation
Published in Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell, LUNG Transplantation, 2016
Glen P. Westall, Miranda A. Paraskeva, Greg I. Snell
Binding of an anti-HLA donor-specific antibody (DSA) with its cognate HLA ligand on the lung allograft triggers a potentially deleterious immune response that results in allograft injury and dysfunction. Amplification of the immune response is dependent on activation of the complement system via the classical pathway. It is now understood that not all DSAs are complement-fixing antibodies; specifically, not all anti-HLA antibodies activate the complement system after binding with HLA molecules. The role of non–complement-fixing antibodies in AMR remains controversial, but an evolving consensus suggests that they are less likely to be alloreactive. The C1q assay aims to distinguish complement-fixing from non–complement-fixing antibodies by identifying only antibodies that can bind to C1q, the first step of the classical complement pathway. C1q-positive anti-HLA DSAs have been shown to be associated with poor outcomes in heart transplantation.14,15 A landmark paper by Loupy and colleagues16 demonstrated that following kidney transplantation, patients with CIq-positive DSAs experienced greater graft loss than did patients with DSAs that were C1q negative. Of note, stratification of patients before transplantation according to C1q positivity did not predict subsequent poor outcomes. Equivalent studies in lung transplantation are awaited.
Graft assessment for acute rejection after intestinal transplantation: current status and future perspective
Published in Scandinavian Journal of Gastroenterology, 2021
Donor specific antibodies are defined as antibodies that are produced against the donor’s antigen (DSA). In transplantation, this definition often refers to antibodies directed towards donor HLA but DSA does also exist against donor ABO antigens and other non-HLA antigens too [37]. These HLA-binding antibodies may exist before the transplantation or develop after the procedure and may persist even after immunosuppression. In solid organ transplantation, DSA has been associated with decreased graft survival and is linked to both acute rejection and chronic rejection after intestinal transplantation [38–41]. In contrast, grafts containing a liver have shown to have a reduced risk for DSA since they are more likely to clear preformed DSAs [39]. The monitoring of DSA is therefore frequently used. However, the optimal management of DSAs is still under debate and improved treatment regimens are emerging [41,42]. The presence of DSA may therefore be viewed as an independent predictor of acute rejection but not as an indicator of rejection itself.
An overview of T follicular cells in transplantation: spotlight on their clinical significance
Published in Expert Review of Clinical Immunology, 2019
Qian Niu, Rens Kraaijeveld, Yi Li, Aleixandra Mendoza Rojas, Yunying Shi, Lanlan Wang, Nicole M Van Besouw, Carla C. Baan
The pathophysiological mechanisms behind humoral rejection are gradually becoming clearer. Recent reports have established a strong association between donor specific antibodies (DSA) that directly target the transplanted organs and markers of humoral immunity, specifically alloantigen specific B cells. As reported by Frank et al. [8] and others [9,10], B cell infiltrates are frequently observed in humoral rejected transplants. These B cells are present in biopsies diagnosed as ABMR [11] but also in specimens of T cell-mediated acute cellular rejection [10,12,13] (Figure 1). More indications of the involvement of T cells in humoral rejection comes from studies by Carpio et al. [12] and de Leur and colleagues [13] reporting that transplant infiltrating CD4+ T cells co-localize with these infiltrated B cells. This suggests a direct pathway of T cell help to B cells in the allograft. This hypothesis is further supported by the discovery that Tfh cells, a specialized T cell subset required for the generation of efficient antibody responses, infiltrate the allograft in follicles where they may locally provide B cell help [14,15]. Proof should come from the functional analysis of Tfh-B cell studies.
JAK3 inhibitor-based immunosuppression in allogeneic islet transplantation in cynomolgus monkeys
Published in Islets, 2019
Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Seong-Jun Kang, Il-Hee Yoon, Hyunwoo Chung, Jiyeon Kim, Eung-Soo Hwang, Jongwon Ha, Chung-Gyu Park
The absolute counts of the T cells, B cells, and NK cells were measured by a flow cytometer (BD FACSCantoTM II; BD Biosciences, San Jose, CA) using suitable fluorochrome-conjugated antibodies. Development of donor-specific antibody (DSA) was assessed by the incubation of donor peripheral blood mononuclear cells (PBMCs) with plasma obtained from the recipient after islet transplantation. After incubation with donor PBMCs, samples were washed extensively and were incubated with FITC-conjugated anti-monkey IgG. After further incubation, samples were washed again, and then the mean fluorescence intensity (MFI) of DSA was measured by flow cytometry. Normal monkey plasma was used as a negative control. The cell count and the MFI data were analyzed with FACSDiva software (BD Biosciences). ELISPOT analysis was performed by the method previously described.19 Briefly, the frequencies of interferon (IFN) γ-secreting donor-specific PBMCs of recipient NHPs were measured using an ELISPOT kit (Mabtech, Nacka Strand, Sweden). The resulting spots were enumerated by a computer-assisted ELISPOT Reader System (AID, Strassberg, Germany).