Anti-HLA Donor-Specific IgG Subclasses and C1q-binding Evolution in Posttransplant Monitoring.

BACKGROUND: The identification of low-level antibodies by single-antigen bead methodology has brought advancements to risk evaluation of kidney transplant recipients. However, the use of mean fluorescence intensity (MFI) to quantify antibodies and to guide therapy is not enough. Notably, immunoglobulin G (IgG) subclass switching is hypothesized to follow a programmed sequence after an emergency signal from the germinal center. In transplantation this process is not clear yet. In the present study, we sequentially evaluate anti-HLA donor specific antibody (DSA) subclasses, their profile changes, and C1q-binding ability and the influence of those characteristics on antibody mediated rejection (AMR) occurrence and allograft function. METHODS: A total of 30 DSA-positive patients were tested for IgG subclass content and C1q-binding in sequential serum samples. RESULTS: Twenty-one patients were DSA-positive before transplant; patients sensitized only by transfusion or pregnancies had IgG1 and/or IgG3, and patients sensitized by both transfusion and pregnancies or previous transplant showed a broader range of IgG subclasses. C1q binding was detected in high MFI made up of IgG1 or multiple IgG subclasses. Only 4 patients were positive for C1q posttransplantation and 3 of these showed an increase in MFI, changes in subclasses patterns, AMR, and allograft dysfunction. CONCLUSIONS: Posttransplant evaluation of DSA subclasses and the ability to bind C1q may be informative for both AMR occurrence and allograft dysfunction. Monitoring these events may help to better define risk and interventional time points.

Complement-fixing donor-specific anti-HLA antibodies and kidney allograft failure.

Detection of donor-specific antibodies (DSA) has improved the risk classification and post-transplant evaluation of kidney recipients. Moreover, assessment of DSA C1q-binding ability has been shown to improve the individual risk classification of transplant patients for allograft loss, especially when detected after transplantation. The aim of this study was to evaluate the additional clinical impact of C1q-binding DSA detection in a population that was extensively monitored for DSA and MFI alterations. Forty-two kidney allograft recipients were followed-up at multiple time points for up to 5 years after transplantation for the presence of anti-HLA DSA-IgG total. The samples that were positive for these antibodies were retrospectively tested for the presence of complement-binding antibodies. Overall, 24 patients presented DSA, 29% (7) of which also produced complement-binding DSA. Compared to patients with non-C1q-binding DSA and non-sensitized patients, patients with C1q-binding DSA after transplantation had the lowest allograft survival rate at 5 years (p = 0.042) and showed a lower estimated glomerular filtration rate (based on the Modification of Diet in Renal Disease formula) during the post-transplant follow-up period (p = 0.01). Thus, post-transplant monitoring for complement-binding DSA is a useful tool for predicting individuals most at risk for allograft failure, and might also be beneficial for evaluation of immunosuppression regimens.

Improvement in renal function in kidney transplant recipients switched from cyclosporine or tacrolimus to belatacept: 2-year results from the long-term extension of a phase II study.

Kidney transplant recipients who switched from a calcineurin inhibitor (CNI) to belatacept demonstrated higher calculated glomerular filtration rates (cGFRs) at 1 year in a Phase II study. This report addresses whether improvement was sustained at 2 years in the long-term extension (LTE). Patients receiving cyclosporine or tacrolimus were randomized to switch to belatacept or continue CNI. Of 173 randomized patients, 162 completed the 12-month main study and entered the LTE. Two patients (n = 1 each group) had graft loss between Years 1-2. At Year 2, mean cGFR was 62.0 ml/min (belatacept) vs. 55.4 ml/min (CNI). The mean change in cGFR from baseline was +8.8 ml/min (belatacept) and +0.3 ml/min (CNI). Higher cGFR was observed in patients switched from either cyclosporine (+7.8 ml/min) or tacrolimus (+8.9 ml/min). The frequency of acute rejection in the LTE cohort was comparable between the belatacept and CNI groups by Year 2. All acute rejection episodes occurred during Year 1 in the belatacept patients and during Year 2 in the CNI group. There were more non-serious mucocutaneous fungal infections in the belatacept group. Switching to a belatacept-based regimen from a CNI-based regimen resulted in a continued trend toward improved renal function at 2 years after switching.

[Laparoscopic cholecystectomy in transplant patients]. / Colecistectomia laparoscópica em transplantados.

OBJECTIVE: This study reviews our experience with laparoscopic cholecystectomy in the treatment of cholelithiasis in transplant patients. METHODS: Demographic data, medications used, and operative and postoperative data of all transplant recipients who were subjected to laparoscopic cholecystectomy for cholelithiasis at our hospital were obtained. RESULTS: A total of 15 transplant patients (13 renal transplantation and 2 bone marrow transplantation) underwent laparoscopic cholecystectomy. All patients were admitted to the hospital on the day of the operation. The immunosuppressive regimen was not modified during hospitalization. Clinical presentation of cholelithiasis was biliary colicky (n=12), acute cholecystitis (n=2), and jaundice (n=1). The operation was uneventful in all patients. Postoperative complications were nausea and vomiting in 2 patients, prolonged tracheal intubation in 1, wound infection in 1 and large superficial hematoma in 1 patient. CONCLUSION: Laparoscopic cholecystectomy is associated to a low morbidity and mortality and good postoperative outcome in transplant patients with uncomplicated cholecystitis.

Colecistectomia laparoscópica em transplantados / Laparoscopic cholecystectomy in transplant patients

OBJETIVO: Apresentar a nossa experiência com a colecistectomia laparoscópica no tratamento da colelitíase em transplantados. MÉTODOS: Dados demográficos, medicamentos utilizados e dados operatórios e pós-operatórios de todos transplantados que foram submetidos à colecistectomia laparoscópica por colelitíase no nosso hospital foram obtidos. Resultados: Quinze pacientes (13 transplantes renais e dois transplantes de medula óssea) foram submetidos à colecistectomia laparoscópica. Todos pacientes foram internados no hospital no dia da operação. O esquema imunossupressor não foi modificado durante a hospitalização. A apresentação clínica da colelitíase foi cólica biliar (n=12), colecistite aguda (n=2) e icterícia (n=1). A colecistectomia transcorreu sem intercorrências em todos pacientes. Complicações pós-operatórias foram náusea e vômitos em dois pacientes, intubação traqueal prolongada em um, infecção de ferida operatória em um e hematoma superficial grande em um paciente. CONCLUSÃO: Colecistectomia laparoscópica é associada à baixa morbidade e mortalidade e bom prognóstico pós-operatório em pacientes transplantados com colecistite não complicada.

OBJECTIVE: This study reviews our experience with laparoscopic cholecystectomy in the treatment of cholelithiasis in transplant patients. METHODS: Demographic data, medications used, and operative and postoperative data of all transplant recipients who were subjected to laparoscopic cholecystectomy for cholelithiasis at our hospital were obtained. RESULTS: A total of 15 transplant patients (13 renal transplantation and 2 bone marrow transplantation) underwent laparoscopic cholecystectomy. All patients were admitted to the hospital on the day of the operation. The immunosuppressive regimen was not modified during hospitalization. Clinical presentation of cholelithiasis was biliary colicky (n=12), acute cholecystitis (n=2), and jaundice (n=1). The operation was uneventful in all patients. Postoperative complications were nausea and vomiting in 2 patients, prolonged tracheal intubation in 1, wound infection in 1 and large superficial hematoma in 1 patient. CONCLUSION: Laparoscopic cholecystectomy is associated to a low morbidity and mortality and good postoperative outcome in transplant patients with uncomplicated cholecystitis.