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Substitution of corticosteroid with everolimus after lung transplantation: a pediatric case report.

We report the case of a 12 year-old lung transplant recipient, in whom compressive epidural lipomatosis secondary to corticosteroid prompted us to replace prednisone with everolimus. Discontinuing corticosteroid treatment after lung transplantation is associated with a risk of graft rejection despite concomitant immunosuppressive therapy with tacrolimus and mycophenolate mofetil. During a follow-up of 18 months with everolimus instead of prednisone, we did not observe graft rejection. In parallel, all symptoms related to epidural compression disappeared within a month.

Histoincompatibility-associated differences in the phenotypes of murine cardiac allograft infiltrating T cells.

Mechanisms of graft rejection may be governed in part by the kind and degree of histocompatibility differences between donor and recipient. Cardiac allograft rejection was studied in three murine models selected to provide disparity at different major histocompatibility complex (MHC), minor lymphocyte stimulating (Mls) and other minor histocompatibility loci. Graft survival for the A.TL to A.TH combination (M3) was significantly longer (median day of rejection 15.0 days) than both the B10.A to AKR (M2) or the C57BL/6 to C3H/HeN (M1) donor-recipient combinations (median days of rejection: 9.0 d…

Negative impact of underlying non-insulin-dependent diabetes mellitus nephropathy on long-term allograft survival in kidney transplantation: a 10-year analysis from a single center.

INTRODUCTION: We analyzed the relationship between underlying nephropathy and long-term outcomes in kidney transplant recipients. METHODS: We retrospectively analyzed data from 678 patients who underwent kidney transplantation (KTx) between 1998 and 2011. Recipients with 13 major nephropathies were evaluated for graft and patient survival, and causes of graft loss. RESULTS: The best 10-year graft survival rates (100%) were in the patients with autosomal-dominant polycystic kidney disease, preeclampsia, Alport syndrome, and purpura nephritis. The worst rate (50.8%) was in patients with non-in

Non-invasive molecular biomarkers for monitoring solid organ transplantation: A comprehensive overview.

Solid organ transplantation is a life-saving intervention for individuals with end-stage organ failure. Despite the effectiveness of immunosuppressive therapy, the risk of graft rejection persists in all viable transplants between individuals. The risk of rejection may vary depending on the degree of compatibility between the donor and recipient for both human leucocyte antigen (HLA) and non-HLA gene-encoded products. Monitoring the status of the allograft is a critical aspect of post-transplant management, with invasive biopsies being the standard of care for detecting rejection. Non-invasive…

Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets.

The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage r … ue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literatu …

Predictive role of pretransplant serum CXCL10 for cardiac acute rejection.

BACKGROUND: The detection of acute rejection in heart transplantation remains an important feature of transplant management, especially in the early phase. Frequent surveillance with endomyocardial biopsy is necessary, even though it is an invasive procedure and carries a certain risk. Hence, noninvasive biomarkers able to predict acute rejection could be a further helpful tool in patient management. The interferon-gamma-inducible chemokine CXCL10 is required for initiation and development of graft failure caused by acute or chronic rejection. It has been reported that CXCL10 serum level is pr

Late acute rejection after liver transplantation impacts patient survival.

Hepatic allograft rejection still remains an important problem following liver transplantation. Early acute rejection, occurring within three months of transplant, is a common event and usually of lesser significance with respect to prognosis than other non-immune-related post-transplant morbidities. However, little is known about late acute rejection (LAR) including factors affecting its occurrence and long-term outcome. In this study, we analyzed LAR including the incidence, clinical risk factors, patient survival, and graft survival. LAR was defined as acute cellular rejection later than si…

[Retrospective evaluation of 2 123 cases of kidney transplantation].

OBJECTIVE: To summarize the experiences in kidney transplantation for 23 years. METHODS: From 1978 to 2001, 2123 kidney transplantations we … were 86.7%/76.3%, 72.5%/67.9% and 69.5%/59.3% respectively. In the 1700 cases (1991 to 2001), acute graft rejection occurred in 252 (14.8%) but no hyper-acute rejection was observed. The 1-, 3-, and 5 year patient/graft survival rates were 98.6%/96.7%, 93.1%/87.3% and 88.1%/83.6% respectively. CONCLUSIONS: Kidney transplantation is a treatment of choice for pati …

Postoperative flow cytometry crossmatch in living donor liver transplantation: clinical significance of humoral immunity in acute rejection.

BACKGROUND: The role of humoral immunity in acute rejection in solid organ transplantation remains controversial, although it is known that the presence of antidonor antibodies may precipitate graft rejection. We investigated the clinical relevance of antidonor humoral immunity for living donor liver transplantation (LDLT) by means of flow cytometry crossmatch (FCXM). METHODS: T cell FCXM using fresh donor peripheral lymphocytes was performed before and up to 1 month after LDLT in 58 patients. Ten patients received ABO-incompatible grafts. IgM and IgG antidonor antibodies were analyzed in rel…

Complement and complement regulatory protein in allogeneic and xenogeneic kidney transplantation.

Kidney transplantation is the most optimal treatment for patients with end-stage renal disease, offering significant improvements in patient outcomes over dialysis. However, the potential for immune rejection, where the recipient's immune system attacks the transplanted kidney, can compromise transplant success. The complement system, a key component of the immune response, plays a crucial role in both acute and chronic rejection, including T-cell- and antibody-mediated rejection. Understanding and controlling the complement system is essential for managing rejection and enhancing graft surviv

Immunoprotection of cellular transplants for autoimmune type 1 diabetes through local drug delivery.

Type 1 diabetes mellitus (T1DM) is an autoimmune condition that results in the destruction of insulin-secreting β cells of the islets of Langerhans. Allogeneic islet transplantation could be a successful treatment for T1DM; however, it is limited by the need for effective, permanent immunosuppression to prevent graft rejection. Upon transplantation, islets are rejected through non-specific, alloantigen specific, and recurring autoimmune pathways. Immunosuppressive agents used for islet transplantation are generally successful in inhibiting alloantigen rejection, but they are suboptimal in hind…

Association of Fc gamma receptor IIA polymorphisms with acute renal-allograft rejection.

Acute rejection is a leading cause of early renal-allograft failure. The human Fc gamma receptor IIA (FcgammaRIIA) forms an essential link between the humoral branch and the effector cells of the immune system. In this study, we examined FcgammaRIIA genotypes in renal-allograft recipients (rejectors) with acute graft rejection and in a number of control groups to investigate a possible association between FcgammaRIIA polymorphism and acute renal-allograft rejection. The distribution of the genotypes in the study patient group differed from the control groups. The frequency of homozygosity for …

Transplantation of the entire small bowel in inbred rats using cyclosporine.

Inbred strains of rats were used to analyze unidirectional host-versus-graft disease (transplant rejection) without graft-versus-host disease in small intestinal transplants and the immunosuppressive properties of cyclosporine (CsA). Forty-six Lewis rats received heterotopic transplants of the entire small bowel in four groups: Lewis-to-Lewis isografts, without CsA; Lewis-to-Lewis isografts, with CsA (15 mg/kg/day); (Lewis X ACI)F1-to-Lewis allografts, without CsA; (Lewis X ACI)F1-to-Lewis allografts, with CsA. Small bowel rejection was associated with gross morphological changes that preceded

An analysis of 100 primary cadaver kidney transplants.

A multifactorial analysis of 100 consecutive first cadaver kidney transplants was done to document the current status of this treatment for … vival without sacrificing kidney graft survival. Clinical studies demonstrating decreases in kidney graft rejection should be controlled for pre-transplant blood transfusions and, possibly, for pre-transplant splenectomy for hypersplenism.

Long-term kidney allograft survival in patients with transplant glomerulitis.

BACKGROUND: Renal transplant glomerulitis (G) is associated with acute antibody-mediated rejection (ABMR) in the presence of donor-specific antibodies. However, the long-term prognosis of isolated G (isG) in the absence of donor-specific antibodies or G in combination with T cell-mediated rejection (TCMR) remains unexplored. METHODS: Seventy recipients with G were included in this retrospective study and subdivided into 3 groups: isG, G with TCMR (G+TCMR), and G with acute ABMR. The control groups were: patients with TCMR Banff type I or II without G (TCMR) and patients without rejection (NR)

Association between increased body mass index, calcineurin inhibitor use, and renal graft survival.

OBJECTIVES: Using data from the US Renal Data System, we examined the relation between body mass index and graft survival as mediated through calcineurin inhibitor use. MATERIALS AND METHODS: Adult patients who received a first kidney-only transplant, with at least 6 months' survival were classified into 5 categories (underweight, normal, overweight, obese, and extremely obese) according to body mass index. Associations between calcineurin inhibitor use, body mass index categories, and outcomes were investigated. RESULTS: Underweight and normal-weight recipients lived longer than the other 3

Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis.

BACKGROUND: Delayed graft function (DGF) is a common complication of renal transplantation. The short-term consequences of DGF are well known, but the long-term relationship between DGF and patient and graft survival is controversial in the published literature. We conducted a systematic review and meta-analysis to precisely estimate these relationships. METHODS: We performed a literature search for original studies published through March 2007 pertaining to long-term (>6 months) outcomes of DGF. The primary outcome was graft survival. Secondary outcomes were patient survival, acute rejection

Therapies for Chronic Allograft Rejection.

Remarkable advances have been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) over the past decades, leading to improved graft outcomes. However, long-term failure is still high and effective treatment for chronic ABMR, an important cause of graft failure, has not yet been identified. Chronic ABMR has a relatively different phenotype from active ABMR and is a slowly progressive disease in which graft injury is mainly caused by de novo donor specific antibodies (DSA). Since most trials of current immunosuppressive therapies for rejection have focused

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… FIGURE 1 Immune mechanisms of graft rejection and therapeutic targets.Plasma exchange (PE) and intravenous immunoglobulin (IVIG) remove DSAs. Anti-CD20 monoclonal antibody (mAb) eliminates B cells, memory B cells, and short-lived plasma cells (PC). …

Resident memory T cells form during persistent antigen exposure leading to allograft rejection.

Tissue-resident memory T cells (TRM) contained at sites of previous infection provide local protection against reinfection. Whether they form and function in organ transplants where cognate antigen persists is unclear. This is a key question in transplantation as T cells are detected long term in allografts, but it is not known whether they are exhausted or are functional memory T cells. Using a mouse model of kidney transplantation, we showed that antigen-specific and polyclonal effector T cells differentiated in the graft into TRM and subsequently caused allograft rejection. TRM identity was…

Kidney Allograft Outcomes in Borderline and T Cell-Mediated Rejection With Microvascular Inflammation.

INTRODUCTION: Microvascular inflammation (MVI) is a hallmark feature of antibody-mediated rejection (ABMR), but its prognostic significance when it occurs with T-cell-mediated rejection (TCMR) in the absence of other ABMR features remains unclear. METHODS: We examined the association between pure TCMR phenotypes, defined by the presence or absence of MVI, and graft survival using restricted mean survival time (RMST), and assessed interactions with rejection involving a "v" lesion. RESULTS: Among 1614 recipients with first biopsy-proven pure TCMR (2010-2023), 85% had no MVI, 8% subthreshold M