Occurrence Of Allograft Rejection Research Articles

Monoclonal gammopathy of undetermined significance coexisting in patients undergoing kidney transplantation does not adversely influence post-graft clinical outcome.

BackgroundManagement of patients with oncohaematological disorders such as monoclonal gammopathy of undetermined significance (MGUS) is a frequent problem in pre-transplant work-up. Insights on disease progression and long-term functional outcomes are still lacking in this setting.MethodsThis was a retrospective analysis on all patients with MGUS who underwent kidney transplant (KT) at our centre between 1 January 2000 and 31 December 2017 (cases, n = 65). Patients were matched with a control group (KTs with similar characteristics but without history of haematological disease, controls, n = 1079). Primary endpoints were graft and patient survival; secondary endpoints were causes of graft failure, patient death, occurrence of allograft rejection, post-transplant neoplasia (not correlated to previous disorder) and/or infectious episodes.ResultsThe MGUS and control groups had a similar mean age [60 (29–79) versus 55.2 (19.3–79.5) years, respectively] and percentage of males (69.2% versus 64.6%, respectively). Median follow-up time since KT was 3.5 years (0–14) in cases and 8.3 years (0–14.9) in controls. All MGUS patients underwent KT following extensive multidiscliplinary investigations. No differences were found between cases and controls regarding patient and graft survival or post-transplant complications except for lower incidence of infections (58.7% versus 69.8%, P = 0.019) and increased use of mTOR inhbitors (30.3% versus 14.7%, P = 0.001) in MGUS. MGUS isotype did not influence graft and patient survival. The absence of difference in patients and graft survival was also confirmed in an adjunctive analysis where MGUS were compared with controls (ratio 1:2) matched for recipient age, gender, number of transplantations and transplant period.ConclusionPatients with MGUS may undergo KT without significantly increased risks of complications, provided that appropriate diagnostic procedures are carefully followed. Multidiscipline-based studies are crucial for establishing well designed pre- and post-transplant protocols for the best management of patients with coexisting MGUS and end-stage renal disease.

Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.

Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.

Decline in rejection in the first year after pediatric cardiac transplantation: A multi-institutional study

Rejection is a major cause of morbidity and mortality after pediatric heart transplantation (HTx). Survival after pediatric HTx has improved over time, but whether there has been an era-related improvement in the occurrence of allograft rejection is unknown. The Pediatric Heart Transplant Study (PHTS) database was queried for patients who underwent HTx from January 1993 to December 2005 to determine the incidence of rejection and identify factors associated with the first episode of rejection in the first year after HTx. Data were reviewed in 1,852 patients from 36 centers. The incidence of rejection declined over 13 years at a rate of -2.58 +/- 0.41 (p < 0.001) from approximately 60% to 40% (p < 0.001). The mean number of episodes of rejection also significantly fell at a rate of -0.05 +/- 0.01 per patient/year from 1.19 to 0.66 (p < 0.001). The incidence of rejection with hemodynamic compromise and death from rejection did not change. Multivariate analysis for the risk of a first rejection episode demonstrated decreased risk of rejection with later year of HTx (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.85-0.91; p < 0.001) and use of mechanical support (OR, 0.65; 95% CI, 0.42-0.99; p = 0.046). Increased risk of rejection was associated with positive donor-specific crossmatch (OR, 1.85; 95% CI, 1.18-2.88; p = 0.007) and older recipient age (OR, 1.05; 95% CI, 1.02-1.07; p < 0.001). Although the overall incidence and prevalence of rejection has substantially decreased over time in pediatric HTx recipients in the first year after HTx, the rate of rejection with hemodynamic compromise or death from rejection remains unchanged.

Temporary withdrawal of immunosuppression for life-threatening infections after liver transplantation.

Temporary withdrawal of immunosuppression for life-threatening infections after liver transplantation.

EXPRESSION OF THE INTERLEUKIN 2 RECEPTOR β CHAIN (p75) IN RENAL TRANSPLANTATION—APPLICABILITY OF ANTMNTERLEUKIN-2 RECEPTOR β CHAIN MONOCLONAL ANTIBODY

The interaction of interleukin 2 with specific cellular receptors plays an essential role in the allostimulated proliferation and differentiation of T cells. Recent chemical linking studies have demonstrated that the human high-affinity IL-2 receptor is a membrane complex composed of at least two distinct subunits, which are the p55 (alpha-chain) and p75 (beta-chain) subunits. The IL-2R beta chain is supposed to play a role in the signal transduction of IL-2, but the exact mechanism is still unknown. In this study, we investigated the effects of a newly established anti-IL-2R beta chain monoclonal antibody (MoAb, TU-27) on the induction of cytotoxic T lymphocytes (CTLs) using the cell-mediated lympholysis (CML) assay. TU-27 in combination with H-31, a MoAb directed against the IL-2R alpha chain, produced inhibition of cytotoxicity, while TU-27 alone could not inhibit cytotoxicity, while TU-27 alone could not inhibit cytotoxicity at any concentration. TU-27 plus H-31 prevented the expansion of CD4+ cells and CD8++ cells in mixed lymphocyte culture (MLC). Furthermore, we examined the serial changes in the expression of the IL-2R beta chain on peripheral blood lymphocytes from renal transplant recipients using two-color immunofluorescence flow cytometry, so as to investigate correlations between IL-2R beta chain expression and the occurrence of allograft rejection. Here, we report that the IL-2R beta chain is expressed on CD4-positive (CD4+) cells and strongly CD8-positive (CD8(+)+) cells in association with acute rejection, indicating that IL-2R beta chain expression appears to increase on alloreactive T cells.