ABO incompatible renal transplants and decreased likelihood for developing immune responses to HLA and kidney self-antigens

Immune responses to HLA and tissue-restricted self-antigens (SAgs) have been proposed to play a role in the pathogenesis of renal allograft (KTx) rejection. However, ABO incompatible (ABOi) KTx recipients (KTxR) following depletion of antibodies (Abs) to blood group antigens had fewer rejections. To determine the mechanisms, pre- and post-transplant sera from ABOi (n = 18) and ABO-compatible (ABOc) (n = 45) KTxR were analyzed for Abs against HLA class I and II by LABScreen single antigen assay. The development of Abs to SAgs was measured by ELISA. Immunity to Collagen IV (Col-IV) and cytokines induced were measured by ELISPOT. While 8/45 (18%) ABOc KTxR developed new donor specific antibodies to HLA (DSA) following transplantation, 0/18 ABOi KTxR developed DSA. ABOi KTxR failed to develop Abs to kidney SAgs (Col-IV and fibronectin (FN)). In contrast, 7 ABOc KTxR developed Abs to both Col-IV and FN. Col-IV stimulation of lymphocytes from ABOc KTxR demonstrated increased IFNγ, IL-17 and decreased IL-10. In contrast ABOi recipients following stimulation with antigens resulted in more IL10 and reduced IFN-γ and IL17 production. At one year, the GFR in ABOi KTxR were significantly better (p < 0.04) than ABOc KTxR. De novo DSA and immune responses to SAgs are reduced or absent in ABOi KTxR which we propose leads to less acute rejection and better long term function following ABOi KTx.     

Successful treatment of Talaromyces marneffei infection in a kidney transplant recipient with voriconazole followed by itraconazole for the first time

Talaromyces (Penicillium) marneffei (T. marneffei) is an important pathogenic thermally dimorphic fungus in Southeast Asia that leads to a life-threatening systemic mycosis in immunodeficient hosts, especially in AIDS patients. With the increasing AIDS epidemic, the number of patients with T. marneffei infections in mainland China has increased rapidly in recent years. The infection can be life-threatening in people with immunodeficiencies, such as HIV, organ transplantations, autoimmune diseases, and malignant tumors. Here, we present a disseminated T. marneffei infection case in a renal transplant recipient successfully treated with voriconazole followed by itraconazole. We describe the patient's clinical progression from onset symptoms to recovery and review the additional 14 published cases with T. marneffei infections in renal transplant recipients. In addition, we discuss the route of infection and treatment strategies of T. marneffei. Our data suggest that patients with kidney transplantations in T. marneffei infection-endemic areas should presume the possibility of infection and initiate appropriate antifungal treatment.     

Infection with hepatitis E virus in kidney transplant recipients in southeastern France

Hepatitis E virus (HEV) is an emerging cause of acute hepatitis in Europe, particularly in southern France, and HEV is a new causative agent of chronic hepatitis and cirrhosis in immunocompromised patients. However, the data regarding HEV infection after kidney transplantation are still scarce with respect to the clinical issues that have been raised, and no study has specifically focused on kidney transplant recipients. This study described the clinical features and outcomes of HEV infections in a cohort of kidney transplant recipients living in southeastern France. The epidemiological, clinical, and virological characteristics of HEV infections diagnosed by PCR over a 53‐month period were retrospectively analyzed in a cohort of 1,350 kidney transplant recipients monitored at the Marseille University Hospital. Sixteen HEV infections were diagnosed, all of which were autochthonous and involved genotype 3 viruses (HEV‐3). Chronic infections occurred in 80% of these patients and resolved in half of the cases after a median time of 39 months. The rate of HEV clearance was 54% after a decrease in the dose of immunosuppressants. One patient developed liver cirrhosis 14 months after infection and experienced acute rejection after a decrease in the dose of immunosuppressants. Autochthonous HEV‐3 infections in kidney transplant recipients progress to chronicity in most cases and might be complicated by early liver cirrhosis. Chronic HEV infection can resolve following the reduction of immunosuppressive therapy, but ribavirin may be required if reduction of the immunosuppressant dose is not associated with HEV clearance or is inappropriate for the patient management. J. Med. Virol. 85:462–471, 2013. © 2012 Wiley Periodicals, Inc.     

Evolution of hepatitis C virus quasispecies in renal transplant patients with de novo glomerulonephritis

Long-term renal allograft survival in kidney transplant recipients infected by hepatitis C virus (HCV) may be influenced by the occurrence of de novo glomerulopathy associated with this virus. Therefore, we studied the evolution of HCV quasispecies in kidney transplant recipients infected by HCV with or without de novo glomerulopathy. The hypervariable region 1 (HVR-1) of the virus envelope was analyzed by cloning and sequencing 20 clones per sample to assess complexity and diversity from six kidney transplant patients who developed de novo glomerulopathy (group I) matched to six kidney transplant recipients without glomerular disease (group II), according to age, time since renal transplantation, and HCV genotype. Two sera were analyzed for each patient: one at the time of renal transplantation and the other at the time of appearance of de novo glomerulopathy, or after a similar duration since transplantation in group II. Overall, there was a significant increase of HCV viremia after the transplantation. This increase did not differ significantly between group I (+0.5 log copies/ml) and group II patients (+1 log copies/ml). The intersample diversity of HCV was similar in the two groups. Complexity and viral diversity were also similar at the time of transplantation. By contrast, complexity, diversity, and the proportion of nonsynonymous substitutions per nonsynonymous site were significantly higher after transplantation in group I patients. Our findings suggest a higher immune response and/or a particular cytokine production in patients developing de novo glomerulopathy rather than a direct effect of HCV on renal cells.     

Fatty acids profile in patients after heart or renal transplantation who developed metabolic complications

Purpose

Diabetes mellitus and hyperlipidemia are frequently observed after organ transplantation. It is known that in these disorders the fatty acid metabolism is impaired. The aim of this study was to compare the fatty acid profile in the heart and renal transplant recipients who developed metabolic disorders since there is no such research available.

Case report: human herpesvirus 6 reactivation associated with colitis in a lung transplant recipient

Whereas human herpesvirus 6 (HHV-6) reactivation is frequent in solid organ transplant recipients, symptomatic disease is rare. A case of colitis associated with HHV-6B reactivation was observed in a lung transplant recipient. This case report suggests that symptomatic HHV-6 infection may occur in the absence of detectable viremia.     

Rhodococcus equi pneumonia in a heart transplant recipient in Korea, with emphasis on microbial diagnosis

Rhodococcus equi is an opportunistic pathogen that usually causes infection in immunocompromised hosts. A heart transplant recipient who had been treated with amphotericin B for pulmonary aspergillosis showed newly developed multiple nodules with a central necrotic area in the right lower lobes. Cultures of several blood samples and an aspirate of the lung nodule yielded a Gram-positive coccobacillary bacterium, which was initially reported as a Corynebacterium species, but was later identified as R. equi by API CORYNE (bioMerieux SA, Marcy l'Etoile, France) and by demonstrating the production of 'equi factor'. The identification was subsequently confirmed by an R. equi -specific polymerase chain reaction (PCR). The patient was successfully treated with ciprofloxacin and azithromycin for 14 weeks. This is the first documented case of R. equi infection in Korea. There is a possibility of underestimation of R. equi infections due to the misidentification of the organism as a contaminating diphtheroid. Because R. equi will not respond to the conventional empirical therapy, the microbiology laboratory should identify R. equi in a timely manner. R. equi -specific PCR will be a useful confirmatory test in human infection.     

Hematopoietic Stem Cell Transplantation in Solid Organ Recipients with Emphasis on Transplant Complications: A Nationwide Retrospective Survey on Behalf of the Japan Society for Hematopoietic Stem Cell Transplantation Transplant Complications Working Group

Little is known about stem cell transplantation in solid organ transplantation (SOT) recipients. We conducted a nationwide retrospective survey of Japan Society for Hematopoietic Stem Cell Transplantation centers. A total of 19 patients who underwent 22 hematopoietic stem cell transplantations (HSCTs) after SOT were identified: 5 autologous HSCTs and 17 allogeneic HSCTs were performed. Patients who underwent autologous HSCT received a liver (n = 4) or kidney (n = 1) transplant. All 5 patients achieved neutrophil engraftment, and 2 of 3 patients with hepatoblastoma were alive at 1 year after HSCT. Allogeneic HSCT was performed in 16 patients (7 liver transplant recipients and 9 kidney transplant recipients). Among these, 2 donors were identical for both transplantations. All but 1 patient achieved neutrophil engraftment. The 5-year overall survival rate was 41.7%, but that in patients with malignant disease (n = 13) was much lower than the overall rate (23.1%). Only 1 patient with malignant disease underwent allogeneic HSCT in nonremission. In allogeneic HSCT after kidney transplantation, post-transplantation (1 year) kidney function in 5 evaluable patients was significantly lower than that before allogeneic HSCT, and 3 patients experienced renal rejection. However, no severe hepatic rejection was noted. In SOT recipients, HSCT is a potentially curable treatment for hematologic disorders, but it must be performed with caution, especially in patients with malignancy.     

A high concentration of TGF-β correlates with opportunistic infection in liver and kidney transplantation

Transforming growth factor-β (TGF-β) has been associated with numerous human infections, but its role in the occurrence of opportunistic infection (OI) after solid organ transplantation remains unexplored. This study aimed to assess the utility of the TGF-β following in vitro stimulation of whole peripheral blood (WPB) as a surrogate biomarker of post-transplant OI in a cohort of liver and kidney recipients.Thirty liver and thirty-one kidney transplant recipients were recruited to be prospectively monitored for one-year post-transplantation. Enzyme-linked immunosorbent assay (ELISA) was performed to calculate IFN-γ, IL-17, IL-10 and TGF-β concentration in the supernatant from the activated WPB.Recipients showed higher TGF-β concentrations compared to IFN-γ, IL-17, IL-10 at baseline, although these differences were not significant between INF and NoINF. However, recipients who developed an OI within the first sixth months had a higher concentration of TGF-β than those without OI. A concentration of TGF-β > 363.25 pg/ml in liver and TGF-β > 808.51 pg/ml in kidney recipients were able to stratify patients at high risk of OI with a sensitivity and specificity above 70% in both types of solid organ transplantations.TGF-β could provide valuable information for the management of liver and kidney recipients at risk of post-transplant infection.     

Activation-induced T cell death, and aberrant T cell activation via TNFR1 and CD95-CD95 ligand pathway in stable cardiac transplant recipients

Specific blockade by antibodies (Abs) utilized in induction therapy may cause activation-induced cell death (AICD) in lymphocytes of transplant recipients, preactivated via CD95 and tumour necrosis factor-alpha receptor type 1 (TNFR1), and reduce allograft rejection frequency. Amongst 618 heart transplant (HTX) patients receiving antithymocytes globulin (ATG) therapy, 14 recipients with IVUS-verified freedom of transplant vasculopathy were studied. The control group contained 14 patients awaiting transplantation, classified by the New York Hearth Association heart failure as class IV. From 618 HTX patients 89% were free of rejection grade ISHLT > or =2-3 within 3-month post transplantation and 86% after one year. The death inducing receptors (DIR) such as CD95, CD95L and soluble TNFR1 were significantly increased in HTX recipients versus controls, as demonstrated by FACS, immunoblotting or ELISA (P < 0.001). The presence of increased DIR and in vivo apoptosis in HTX recipients, indicated by annexin-V binding, was further confirmed by the presence of high concentration of histones in the sera of patients. ATG, anti-IL-2R and OKT-3 Abs inhibited cell proliferation in a dose-dependent manner. The induction of apoptosis and/or necrosis was demonstrated in cells cultured with these Abs by annexin-V and 7-aminoactinomycin staining, respectively. Our findings demonstrate that T cells from HTX recipients express high level of CD95, CD95L and soluble TNFR1, and undergo apoptosis and AICD. These cells recognizing donor alloantigens may be selectively eliminated in vivo, and should be responsible for the observed immunological unresponsiveness, indicated by low rejection rates in our patient cohort treated by conventional triple therapy.     

Review: cognitive and psychological outcomes in pediatric heart transplantation

OBJECTIVE: To review empirical literature investigating the cognitive and psychological effects of pediatric heart transplantation. METHODS: Electronic and library searches were used to identify empirical studies examining the cognitive and psychological effects of pediatric heart transplantation. Only studies investigating cognitive or psychological outcomes, either prospectively or cross-sectionally, were reviewed. RESULTS: Preliminary findings suggest that children and adolescents generally functioned within the normal range on most measures of cognitive functioning post-transplant. However, a complicated transplant course caused by infections or rejections may place these recipients at increased risk for cognitive difficulties post-transplant. Studies also suggested that approximately 20%-24% of pediatric heart transplant recipients experienced significant symptoms of psychological distress (e.g., anxiety, depression, behavior problems) during the first year post-transplant. CONCLUSIONS: Research suggests that some recipients are at risk for cognitive and psychological difficulties post-transplant and may require additional academic remediation and/or psychological intervention to address these challenges. Given the limited number of empirical studies available at this time, continued research investigating cognitive and psychological outcomes following pediatric heart transplantation is needed.     

Colonization and infection due to carbapenemase-producing Enterobacteriaceae in liver and lung transplant recipients and donor-derived transmission: a prospective cohort study conducted in Italy

Objectives

A prospective cohort study was conducted in Italy in order to describe the microbiologic aspects of colonization/infection by carbapenemase-producing Enterobacteriaceae (CPE) in donors and recipients of lung and liver transplants and the possible CPE transmission from donors to recipients.

Surgical Treatment for Severe Heart Failure: Recent Progress in Treatment Strategy and its Present Status in Japan

Chronic intractable heart failure that is unresponsive to maximum medical therapy can have a wide variety of causes; these include advanced valvular diseases and severe myocardial ischemia, ischemic cardiomyopathy (ICM) in heart failure following extensive myocardial infarction, chronic heart failure due to dilated cardiomyopathy (DCM) in which the myocardium itself is progressively damaged or the acute aggravation of the latter. Heart transplantation has long been considered the only useful treatment for patients with heart failure due to ICM- and DCM-induced severe left ventricular hypofunction. However, because of the extremely limited number of heart transplant donors, other surgical treatments have also been attempted. In this communication, we provide an overview of the current situation with regard to left ventriculoplasty and heart transplantations, as well as of the treatment of severe heart failure using ventricular assist devices, which have recently shown remarkable progress.     

Cardiac antibody production to self-antigens in children and adolescents during and following the correction of severe diabetic ketoacidosis

Diabetic cardiomyopathy (DC) is an independent phenotype of diabetic cardiovascular disease. The understanding of the pathogenesis of DC in young patients with type 1 diabetes (T1D) is limited. The cardiac insults of diabetic ketoacidosis (DKA) and progression of DC could include development of antibodies (Abs) to cardiac self-antigens (SAgs) such as: myosin (M), vimentin (V) and k-alpha 1 tubulin (Kα1T). The goal of this study is to determine if the insults of severe DKA and its inflammatory cascade are associated with immune responses to SAgs. Development of Abs to the SAgs were determined by an ELISA using sera collected at three time points in relation to severe DKA (pH?p?=?0.0452). A significant association is present between T1D duration (<3 years) and Abs to Kα1T (p?=?0.0134). Further, Abs to MYO and VIM are associated with inflammatory cytokines. We propose that severe DKA initiates the synthesis of Abs to cardiac SAgs that are involved in the early immunopathogenesis of DC in young patients with T1D.     

Hepatitis B vaccination of immunosuppressed heart transplant recipients with the vaccine Hepa Gene 3 containing pre-S1, pre-S2, and S gene products

The antibody response of immunosuppressed heart transplant recipients to vaccination with the hepatitis B (HB) virus vaccine Hepa Gene 3 (HG-3), containing HB virus pre-S1, pre-S2, and S gene products, was examined. Three heart transplant recipients who had been vaccinated preoperatively against HB responded well to the vaccination. Five of 38 patients (13.2%) vaccinated postoperatively before HG-3 vaccination with the second-generation vaccine Gen-H-B-Vax-D (37 without and 1 with detectable anti-HBs response) and 3 of 24 (12.5%) without previous HB vaccination developed protective anti-HBs titers (greater than 10 U/1) after immunization with the HG-3 vaccine. The l low response rate (8/62, 12.9%) found for postoperatively vaccinated patients indicates that heart transplant recipients should be vaccinated against HB before immunosuppressive medication.Abbreviations HB hepatitis B - HG-3 Hepa gene 3     

Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients

We review the experience at our institution with galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in the diagnosis of invasive pulmonary aspergillosis (IPA) among solid-organ transplant recipients. Among 81 patients for whom BAL GM testing was ordered (heart, 24; kidney, 22; liver, 19; lung, 16), there were five cases of proven or probable IPA. All five patients had BAL GM of > or = 2.1 and survived following antifungal therapy. The sensitivity, specificity, and positive and negative predictive values for BAL GM testing at a cutoff of > or = 1.0 were 100%, 90.8%, 41.7%, and 100%, respectively. The sensitivity of BAL GM testing was better than that of conventional tests such as serum GM or BAL cytology and culture. Moreover, a positive BAL GM test diagnosed IPA several days to 4 weeks before other methods for three patients. Twelve patients had BAL GM of > or = 0.5 but no evidence of IPA. Among these, lung transplant recipients accounted for 41.7% (5/12) of the false-positive results, reflecting frequent colonization of airways in this population. Excluding lung transplants, the specificity and positive predictive value for other solid-organ transplants increased to 92.9% and 62.5%, respectively (cutoff, > or = 1.0). In conclusion, BAL GM testing facilitated more-rapid diagnoses of IPA and the institution of antifungal therapy among non-lung solid-organ transplant recipients and helped to rule out IPA.     

The Lewis antigen system and its relevance for clinical transplantation.

The influence of the Lewis blood group system on transplant survival was studied retrospectively in 161 kidney transplantations. Le (a-b+) recipients had significantly higher graft survival rates than Le (a+b-) or Le (a-b-) recipients. From the known distribution of the Lewis blood groups among the European population, a high percentage of Lewis-compatible transplants would be expected among Le (a-b+) recipients in contrast to the Le (a+b-) and Le (a-b-) recipients. Other factors which are known to influence transplant prognosis such as HLA-match between donor and recipient, ischemic time of the transplants and pretransplant blood transfusions did not differ significantly in any of the three groups studied. Our data again suggest the relevance of the Lewis blood group system for clinical kidney transplantation. The findings should be confirmed by prospective typing of donor and recipient for Lewis antigens.