BACKGROUND: Steroid pulse therapy has been used for patients with acute rejection after kidney transplantation. The ABCB1 gene codes for P-glycoprotein, a transporter that is involved in the metabolism of steroids. However, the role of ABCB1 polymorphisms has not been investigated in patients with acute rejection after kidney transplantation. METHODS: Among 763 patients that received kidney or simultaneous pancreas-kidney transplantation at Seoul National University Hospital between May 1996 and July 2009, 684 patients agreed to genetic sampling for polymorphisms. Acute rejection was defined as biopsy-proven, acute cellular rejection with increased serum creatinine, or in the context of delayed or slow graft function. Steroid-resistance was defined as no improvement in serum creatinine, need for additional OKT3 or ATG treatment, or repeated acute rejection within 30 days. Three polymorphisms of ABCB1 gene (C1236T, C3435T, G2677T/A) were assessed. RESULTS: C allele frequency of C3435T was 59.3% and of C1236T 40.1%. Patients who were steroid-resistant (n=37) had higher serum creatinine at kidney biopsy compared to those who were steroid-sensitive (n=49, P<0.001). The frequency of ABCB1 gene polymorphisms (C1236T and C3435T) did not differ significantly between patients who were steroid-sensitive and those who were resistant. An association with G2677T/A could not be analyzed due to a high failure rate of genotyping. CONCLUSIONS: ABCB1 gene polymorphisms (C1236T and C3435T) were not associated with steroid resistance in patients with acute cellular rejection after kidney transplantation.
Biopsy ; Creatinine ; Gene Frequency ; Humans ; Kidney ; Kidney Transplantation ; Muromonab-CD3 ; P-Glycoprotein ; Rejection (Psychology) ; Steroids ; Transplants

C4d is produced from the direct interaction between antibodies and tissue injury at an antibody binding site in a graft. C4d deposition along peritubular capillaries (PTCs) in a renal allograft is a characteristic finding of antibody-mediated rejection (AMR), and is a useful diagnostic tool of AMR. The C4d along PTCs is associated with poor graft survival. Therefore C4d is regarded as a biomarker of AMR and was included in the diagnosis criteria of AMR at 2007 Banff conference. However, although C4d assay is widely used, it has several limitations. ABO-incompatible transplantations develop C4d along the PTCs in the majority of grafts but this seems to be graft accommodation rather than AMR. Recent studies reported that more than half of renal allograft biopsies with chronic AMR were C4d-negative. Without treatment, the C4d-negative AMR can cause scarring within the graft, transplant glomerulopathy (TG) or even graft loss. C4d is not a certain indicator of antibody-mediated rejection and C4d staining is not always highly sensitive for detecting AMR. Measuring endothelial gene expression in kidney graft biopsies with alloantibody can be another sensitive and specific method to diagnose AMR and predict graft outcomes. Because of these complexities, at the 2011 Banff meeting, criteria for diagnosis of chronic AMR in the kidney were refined, and the need for inclusion of C4d-negative AMR in the Banff classification was investigated.
Antibodies ; Binding Sites, Antibody ; Biopsy ; Capillaries ; Cicatrix ; Factor IX ; Gene Expression ; Graft Survival ; Kidney ; Rejection (Psychology) ; Transplantation, Homologous ; Transplants

BACKGROUND: Heart transplantation in elderly patients has raised concerns because of co-morbidities and limited life expectancy in the era of donor shortage. We examined the outcomes after heart transplantation in elderly patients. MATERIALS AND METHODS: From March 1994 to December 2011, 81 patients (male:female=64:17, 49.1+/-14.0 years) underwent heart transplantation. The outcomes after heart transplantation in the younger patients (<60 years; group Y, n=60) were compared with those in the elderly patients (> or =60 years; group O, n=21). The follow-up duration was 51.8+/-62.7 months. RESULTS: Early mortality (< or =30 days) occurred in 5.0% (3/60) and 4.8% (1/21) of groups Y and O, respectively (p>0.999). There were no differences in overall survival between the two groups (p=0.201). Freedom from rejection was higher in group O than in group Y (p=0.026). Multivariable analysis revealed that age > or =60 years was not a significant risk factor for long-term survival; postoperative renal failure was the only significant risk factor for long-term survival (p=0.011). CONCLUSION: Early and mid-term results of heart transplantation in elderly patients were similar to those in younger patients.
Aged ; Follow-Up Studies ; Freedom ; Heart ; Heart Transplantation ; Humans ; Life Expectancy ; Rejection (Psychology) ; Renal Insufficiency ; Risk Factors ; Tissue Donors

The repair of abdominal aortic aneurysm (AAA) in patients with functioning renal transplant is critical because it is important to avoid ischemic and reperfusion injury to the transplanted kidney. Endovascular aneurysm repair (EVAR) avoids aortic cross clamping and can prevent renal graft ischemia. Here we report the endovascular management and outcome of AAA in two renal transplant patients using a bifurcated aortic stent graft. One patient underwent EVAR using a small amount of contrast (30 mL) due to decreased renal function resulting from chronic rejection. Another patient had EVAR performed with iliac conduit because of the heavily calcified, stenotic lesion of external iliac artery. EVAR in patients with a renal transplant is a feasible option without impairing renal arterial flow.
Aneurysm ; Aortic Aneurysm, Abdominal ; Constriction ; Endovascular Procedures ; Humans ; Iliac Artery ; Ischemia ; Kidney ; Kidney Transplantation ; Rejection (Psychology) ; Reperfusion Injury ; Stents ; Transplants

PURPOSE: There is controversy concerning the effect of a positive T-lymphocytotoxic crossmatch (TLC) on clinical outcomes in adult living donor liver transplantation (LDLT). The aim of this study was to investigate the effect of TLC on clinical outcomes in LDLT and to determine how long a pretransplant positive TLC continues after liver transplantation (LT). METHODS: Between January 2005 and June 2010, 219 patients underwent adult LDLT at National Cancer Center. The TLC test was routinely performed before LDLT. TLC test results were positive in 8 patients (3.7%). Patients were divided into 2 groups according to the result of TLC: positive TLC (n = 8) and negative TLC (n = 211) groups. All patients with a pretransplant positive TLC (n = 6) underwent a TLC test every week until negative conversion of TLC, except 2 patients who refused to receive the TLC test. RESULTS: Acute cellular rejection, surgical complications and patient or graft survival were not significantly different between both groups. All patients with a positive TLC (n = 6) had a posttransplant negative TLC. The median time to negative conversion of TLC was 1.5 weeks (range, 1 to 3 weeks). CONCLUSION: A pretransplant positive TLC does not affect clinical outcomes in adult LDLT. Moreover, T-lymphocytotoxic cross-reactivity disappeared within 3 weeks (range, 1 to 3 weeks) after LT.
Adult ; Graft Survival ; Humans ; Liver ; Liver Transplantation ; Living Donors ; Rejection (Psychology)

BACKGROUND: Ischemic injury and the rejection process are the main reasons for graft failure in tracheal transplantation models. To enhance the acceptance, we investigated the influence of mesenchymal stem cells (MSCs) on tracheal allografts. METHODS: Extracted tracheal grafts from New Zealand white rabbits were cryopreserved for 4 weeks and orthotopically transplanted (control group A, n=8). In group B (n=8), cyclosporin A (CsA, 10 mg/kg) was injected daily into the peritoneal cavity. In group C (n=8), MSCs (1.0x10(7) cells/kg) from the same donor of the tracheal allograft, which had been pre-cultured for 4 weeks, were infused intravenously after transplantation. In group D (n=8), MSCs were infused and CsA was injected daily. Four weeks after transplantation, gross and histomorphological assessments were conducted for graft necrosis, measuring the cross-sectional area of the allograft, determining the degree of epithelization, lymphocytic infiltration, and vascular regeneration. RESULTS: The morphologic integrity of the trachea was retained completely in all cases. The cross-sectional areas were decreased significantly in group A (p=0.018) and B (p=0.045). The degree of epithelization was enhanced (p=0.012) and the lymphocytic infiltration was decreased (p=0.048) significantly in group D compared to group A. The degree of vascular regeneration did not differ significantly in any of the groups. There were no significant correlations among epithelization, lymphocytic infiltration, and vascular regeneration. CONCLUSION: The administration of MSCs with concurrent injections of CsA enhanced and promoted epithelization and prevented lymphocytic infiltration in tracheal allografts, allowing for better acceptance of the allograft.
Cryopreservation ; Cyclosporine ; Mesenchymal Stromal Cells ; Necrosis ; Peritoneal Cavity ; Rabbits ; Regeneration ; Rejection (Psychology) ; Tissue Donors ; Trachea ; Transplantation, Homologous ; Transplants

IL-12 is a secretory heterodimeric cytokine composed of p35 and p40 subunits. IL-12 p35 and p40 subunits are sometimes produced as monomers or homodimers. IL-12 is also produced as a membrane-bound form in some cases. In this study, we hypothesized that the membrane-bound form of IL-12 subunits may function as a costimulatory signal for selective activation of TAA-specific CTL through direct priming without involving antigen presenting cells and helper T cells. MethA fibrosarcoma cells were transfected with expression vectors of membrane-bound form of IL-12p35 (mbIL-12p35) or IL-12p40 subunit (mbIL-12p40) and were selected under G418-containing medium. The tumor cell clones were analyzed for the expression of mbIL-12p35 or p40 subunit and for their stimulatory effects on macrophages. The responsible T-cell subpopulation for antitumor activity of mbIL-12p35 expressing tumor clone was also analyzed in T cell subset-depleted mice. Expression of transfected membrane-bound form of IL-12 subunits was stable during more than 3 months of in vitro culture, and the chimeric molecules were not released into culture supernatants. Neither the mbIL-12p35-expressing tumor clones nor mbIL-12p40-expressing tumor clones activated macrophages to secrete TNF-alpha. Growth of mbIL-12p35-expressing tumor clones was more accelerated in the CD8+ T cell-depleted mice than in CD4+ T cell-depleted or normal mice. These results suggest that CD8+ T cells could be responsible for the rejection of mbIL-12p35-expressing tumor clone, which may bypass activation of antigen presenting cells and CD4+ helper T cells.
Animals ; Antigen-Presenting Cells ; Clone Cells ; Corynebacterium ; Fibrosarcoma ; Interleukin-12 ; Interleukin-12 Subunit p35 ; Interleukin-12 Subunit p40 ; Macrophages ; Mice ; Rejection (Psychology) ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Tumor Necrosis Factor-alpha

OBJECTIVES: The Patient rejection scale (PRS) has been reported as a valid tool for the assessment of rejecting feelings of family respondents toward schizophrenics who return to live with their families. The aim of this study was to assess the reliability and validity of the Korean-version of PRS (K-PRS). METHODS: A sample of 272 primary caregivers of schizophrenics completed the K-PRS and the data were analyzed for internal consistency and factor structure. Additionally 117 caregivers refilled K-PRS after two weeks for test-retest reliability. To test for validity, Family Questionnaire (FQ), Drug Attitude Inventory-10 (DAI-10) and the Scale to Assess Unawareness of Mental Disorder (SUMD) were administered. RESULTS: Internal consistency of K-PRS was good (Cronbach' alpha=0.787) and principal component factor analysis revealed the three-factor structure. The K-PRS also showed reasonable test-retest reliability (r=0.795). Convergent validity was examined through correlations between the K-PRS and the FQ-criticism subscale (r=0.78). Divergent validity was examined through correlations between the K-PRS and KDAI-10 (r=-0.02, p=0.001), and between the K-PRS and SUMD-K (r=-0.02, p=0.796). CONCLUSION: The Korean version of PRS proved to be a reliable and valid instrument measuring rejecting feelings in relatives of Korean patients with schizophrenia.
Caregivers ; Surveys and Questionnaires ; Humans ; Mental Disorders ; Rejection (Psychology) ; Reproducibility of Results ; Schizophrenia

Transplant biopsy has always been the gold standard for assessing the immune response to a kidney allograft (Chandraker A: Diagnostic techniques in the work-up of renal allograft dysfunction-an update. Curr Opin Nephrol Hypertens 8:723-728, 1999). A biopsy is not without risk and is unable to predict rejection and is only diagnostic once rejection has already occurred. However, in the past two decades, we have seen an expansion in assays that can potentially put an end to the "drug level" era, which until now has been one of the few tools available to clinicians for monitoring the immune response. A better understanding of the mechanisms of rejection and tolerance, and technological advances has led to the development of new noninvasive methods to monitor the immune response. In this article, we discuss these new methods and their potential uses in renal transplant recipients.
Biopsy ; Kidney ; Monitoring, Immunologic ; Organothiophosphorus Compounds ; Rejection (Psychology) ; Transplantation, Homologous ; Transplants

Antibody-mediated rejection (AMR) by preformed and/or de novo human leukocyte antigen alloantibodies is a leading cause of early and late allograft loss. In this review, we describe strategic approaches to various forms of AMR in clinical settings that are not based on pathologic classification, which is controversial for atypical AMR (C4d-, DSA-, subclinical etc.). For acute AMR, a variety of modalities like plasmapheresis, intravenous immunoglobulin, and anti-CD20 antibodies have been utilized singly, or in combination, with variable results; however, no established treatment for chronic AMR is known. Significant research efforts are being made for developing new and novel therapies. Improvements in clinical outcomes can be expected from studies evaluating innovative therapeutic concepts, such as proteasome inhibition or complement-blocking agents.
Antibodies ; Humans ; Immunoglobulins ; Isoantibodies ; Leukocytes ; Plasmapheresis ; Proteasome Endopeptidase Complex ; Rejection (Psychology) ; Transplantation, Homologous