Lymphatic Reconstruction in Kidney Allograft Aggravates Chronic Rejection by Promoting Alloantigen Presentation

Chronic rejection of the renal allograft remains a major cause of graft loss. Here, we demonstrated that the remodeling of lymphatic vessels (LVs) after their broken during transplantation contributes to the antigen presenting and lymph nodes activating. Our studies observed a rebuilt of interrupted lymph draining one week after mouse kidney transplantation, involving preexisting lymphatic endothelial cells (LECs) from both the donor and recipient. These expanding LVs also release C-C chemokine ligand 21 (CCL21) and recruit CCR7+ cells, mainly dendritic cells (DCs), toward lymph nodes and spleen, evoking the adaptive response. This rejection could be relieved by LYVE-1 specific LVs knockout or CCR7 migration inhibition in mouse model. Moreover, in retrospective analysis, posttransplant patients exhibiting higher area density of LVs presented with lower eGFR, severe serum creatinine and proteinuria, and greater interstitial fibrosis. These results reveal a rebuilt pathway for alloantigen trafficking and lymphocytes activation, providing strategies to alleviate chronic transplantation rejection.

Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes

Allogeneic islet transplantation has become an effective treatment option for severe Type 1 diabetes with intractable impaired awareness due to hypoglycemic events. Although current immunosuppressive protocols effectively prevent the acute rejection associated with initial T cell activation in recipients, chronic rejection has remained an obstacle for achieving long-term allogeneic islet engraftment. The development of donor-specific immune tolerance to the allograft is the ultimate goal given its potential ability to overcome chronic rejection and disregard the need for maintenance immunosuppression, which may be toxic to islet grafts. Recently, a breakthrough in tolerance induction during allogeneic islet transplantation using apoptotic donor lymphocytes (ADLs) in a non-human primate model had been reported. Several studies have suggested that the clonal depletion, anergy, and expansion of the antigen-specific regulatory immune network are the mechanisms for donor-specific tolerance with ADLs, which act synergistically to induce robust transplant tolerance. This achievement represents a huge step forward toward the clinical application of immune tolerance induction. We herein summarize the reported operational induction therapies in islet transplantation using the ADLs. Moreover, a few obstacles for the engraftment of transplanted islets, such as islet immunogenicity and instant blood-mediated response, which need to be resolved in the future, are also discussed.

Leydig cell tumor of the testis: an incidental finding at 18F-FDG PET/CT imaging

Background Leydig cell tumors (LCTs) represent the most common form of stromal tumors. We reported the 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) findings of a patient with testicular LCT. Case presentation A 50-year-old man with a history of end-stage renal disease and renal transplantation 19 years ago. One year earlier, he started to have a chronic rejection. During the investigation to determine the cause of chronic rejection, a suspicious lesion in the graft with a collection around it was seen on ultrasound (US) images, raising the possibility of post-transplant lymphoproliferative disorder (PTLD). The patient was referred for further evaluation by whole body 18F-FDG PET/CT imaging. The image finding revealed an incidental hypermetabolic focal lesion in the right testicle—no other specific findings in the remaining parts of the body nor definitive FDG avid lymphadenopathy to suggest PTLD. Testicular US was requested and showed a well-defined right-sided heterogeneous hypoechoic intratesticular focal mass at the upper pole of the right testis with significant internal vascularity on the color Doppler imaging. The patient underwent a right radical orchidectomy, and the tumor was pathologically confirmed as an LCT. Conclusion In our case, 18F-FDG-PET/CT has been helpful in incidentally detecting this rare testicular tumor in a patient with suspected PTLD.

Graft rejection after pediatric living related liver transplantation

Background: Rejection is an important adverse event after pediatric liver transplantation (LT). Aim: We aimed to study the incidence and risk factors for post-transplant rejection in pediatrics. Methods: The study included 40 pediatric patients underwent LT. All patients' records were reviewed. A wide range of potential risk factors for rejection, were recorded. Results: Rejection occurred in 13/40 (32.5%) of recipients. For the 13 rejecters, a total of 24 rejection attacks have occurred. 25% of which occurred during the 1st month post-LT. Acute rejection accounted for 54% of total rejection attacks, while chronic rejection occurred in 46%. LT for biliary atrasia (BA) was a significant risk factor for rejection. The means of transaminases levels were 268 ± 141 (IU/L) AST and 221 ± 119 (IU/L) ALT, biliary enzymes were 962 ± 687 (IU/L) for the ALKP and 485 ± 347 (IU/L) for the GGT, total BIL was 6.5 ± 7.1 (mg/dl), and FKL levels were 10.4 ± 5.6 (ng/ml) during the rejection attacks. Chronic rejection contributed to death of only one of the cases. Conclusion: BA was a significant risk for rejection. Elevated transaminases and biliary enzymes but not FK trough level is alarming signs for presence of rejection. Keywords: liver transplantation; pediatrics; rejection.