Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma.

We generated a comprehensive atlas of the immunologic cellular networks within human malignant pleural mesothelioma (MPM) using mass cytometry. Data-driven analyses of these high-resolution single-cell data identified 2 distinct immunologic subtypes of MPM with vastly different cellular composition, activation states, and immunologic function; mass spectrometry demonstrated differential abundance of MHC-I and -II neopeptides directly identified between these subtypes. The clinical relevance of this immunologic subtyping was investigated with a discriminatory molecular signature derived through comparison of the proteomes and transcriptomes of these 2 immunologic MPM subtypes.

Can we use dilution-titration studies to identify clinically relevant HLA antibody specificities?

These data suggest the presence of virtual crossmatch positive, low titer donor specific anti-human leukocyte antigen antibody (DSA) positive sera does not guarantee that real-time crossmatches will be positive. DSA that are present at an undiluted concentration but absent at a 1:8 or 1:16 dilution may not have to be considered unacceptable. This would allow potential recipients wider access to donor organs by reducing the number of listed unacceptable antigens.

Comparing an early corticosteroid/late calcineurin-free immunosuppression protocol to a sirolimus-, cyclosporine A-, and prednisone-based regimen for pancreas-kidney transplantation.

Aim: A prednisone and calcineurin inhibitor (CNI)-free protocol was compared with a sirolimus, cyclosporine A (CsA), and prednisone-based immunosuppressive regimen for simultaneous pancreas-kidney transplantation (SPK).

Methods: A nonrandomized, single-center, sequential study enrolled low-immune responder SPK transplant recipients. The prednisone/CNI-free (minimization) group of 22 patients received thymoglobulin followed by sirolimus and reduced-dose CsA.

The crossmatch may still be the most clinically relevant histocompatibility test performed.

We evaluated patient sera for flow PRA, FCXM, and end-point donor-antigen titer, and we correlated the results with graft survival. You cannot accurately predict a positive or negative FCXM result-not even when the sera have donor-specific antigens-unless you actually perform a crossmatch. Using fluorescence intensity as a surrogate for antibody concentration does not correlate quantitatively with the occurrence of a positive or negative crossmatch.

Risk factors for impaired wound healing in sirolimus-treated renal transplant recipients.

Aim: As sirolimus has been implicated in impaired wound healing, the aim of this study was to evaluate risk factors for wound complications after renal transplantation in patients treated with this drug de novo.

Methods: This single center retrospective review of wound complications included 194 renal transplant recipients, all of whom received sirolimus immunosuppression in combination with reduced doses of cyclosporine (CsA) and corticosteroids de novo. A wound complication was defined as an infection, incisional hernia, or lymphocele.

Understanding the sensitized patient.

New technologies have resulted in the ability to identify the presence of IgG human leukocyte antigen (HLA) or non-HLA antibodies in the sera of potential solid organ transplant recipients. Knowledge of the presence of these antibodies, their antigen specificities, and strength (titer) is crucial to understanding a patient's state of immunologic sensitization and reactivity. Finally, these data, when correlated with sensitive crossmatch results, allow clinicians to make more knowledgeable clinical decisions when paring donors and recipients for transplant.

Long-term outcomes of single paediatric vs. ideal adult renal allograft transplants in adult recipients.

Aim: To compare the outcomes of single paediatric vs. adult kidneys transplanted into adult recipients.

Methods: A retrospective single-centre review of 38 single cadaver kidney transplants from donors less than five yr of age to wait-listed patients of low body mass index (BMI).

Pancreas transplantation utilizing thymoglobulin, sirolimus, and cyclosporine.

Background: This study aims to determine the impact of thymoglobulin-sirolimus-cyclosporine immunosuppression on the alloimune response of pancreas-kidney transplant recipients.

Methods: Thirty-six pancreas transplant recipients received an induction protocol of thymoglobulin, sirolimus, reduced-dose cyclosporine, and corticosteroids. Ten recipients were also enrolled in a study to measure immune responsiveness.

Allograft rejection requires STAT5a/b-regulated antiapoptotic activity in T cells but not B cells.

STATs play key roles in immune function. We examined the role of STAT5a/b in allograft rejection. STAT5a/b-deficient mice showed a 4-fold increased survival time of heart allografts (p < 0.

The selective use of basiliximab versus thymoglobulin in combination with sirolimus for cadaveric renal transplant recipients at low risk versus high risk for delayed graft function.

Background: We previously reported that the use of basiliximab together with sirolimus permits a window of recovery from delayed graft function before the introduction of reduced-dose cyclosporine. The present study reviews our experience with the substitution of thymoglobulin for basiliximab as induction therapy for recipients at increased risk for early acute rejection episodes.

Methods: We retrospectively reviewed 145 cadaveric renal allograft recipients who received either basiliximab (n=115) or thymoglobulin (n=30) in combination with sirolimus and prednisone, followed by delayed introduction of reduced doses of cyclosporine.

Evolution of HLA antibody detection: technology emulating biology.

New technological advances in the field of histocompatibility have provided an approach to systematically address the specificity of positive lymphocyte crossmatches. These approaches can now confirm whether a positive crossmatch is (or is not) due to class I and/or class II antibodies directed against donor HLA antigens. The information gained from the application of these sensitive and specific technologies can be used to predict crossmatch results for highly sensitized patients.

Antibody-mediated rejection criteria - an addition to the Banff 97 classification of renal allograft rejection.

Antibody-mediated rejection (AbAR) is increasingly recognized in the renal allograft population, and successful therapeutic regimens have been developed to prevent and treat AbAR, enabling excellent outcomes even in patients highly sensitized to the donor prior to transplant. It has become critical to develop standardized criteria for the pathological diagnosis of AbAR. This article presents international consensus criteria for and classification of AbAR developed based on discussions held at the Sixth Banff Conference on Allograft Pathology in 2001.

Thymoglobulin, sirolimus, and reduced-dose cyclosporine provides excellent rejection prophylaxis for pancreas transplantation.

Background: We investigated a novel immunosuppressive protocol including thymoglobulin induction in combination with sirolimus and corticosteroids, followed by introduction of markedly reduced exposures to cyclosporine to prevent pancreas-transplant rejection.

Methods: A 7-day course of thymoglobulin (1.5 mg/kg per day) was begun on postoperative day (POD) 0, together with 15 mg of sirolimus on POD 1, and followed by 5 mg per day, targeting these doses to achieve a trough of 10 to 20 ng/mL.