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Rogers N.M.,Central Northern Adelaide Renal and Transplantation Services | Rogers N.M.,University of Adelaide | Lawton P.D.,Renal Services | Jose M.D.,Menzies Research Institute

Introduction: Plasma cell-rich rejection is a distinct histological phenomenon associated with poor renal allograft outcomes. Aboriginal and Torres Straight Islander (ATSI) transplant recipients have poorer allograft survival and higher rates of acute rejection. We sought to determine whether a higher incidence of plasma cell-rich infiltrates (PCIR) could account for poorer survival. Methods: Renal transplant biopsies performed in recipients from the Northern Territory of Australia between 1985 and 2007 were reviewed and correlated with outcome. Biopsies were designated PCIR positive when plasma cells constituted >10% of the interstitial infiltrate. Results: Four hundred and seventy-seven biopsies from 177 recipients (108 ATSI) were performed. Median graft survival was shorter for recipients with PCIR: 4.0 years (interquartile range 2.18-6.41) versus 5.4 years (2.0-9.99) (P = 0.013). ATSI recipients had higher rates of plasma cell-rich rejection (RR 1.76, 95% CI 1.43-2.17, P< 0.0001), which occurred earlier (251 vs 869 days, P = 0.03) compared with non-indigenous recipients. On multivariate analysis, PCIR did not independently influence allograft survival. There was a correlation between PCIR and panel reactive antibody peak >20% (RR 1.29, 95% CI 1.03-1.56, P = 0.025), ≥5 human leukocyte antigen mismatches (RR 1.91, 1.41-2.58, p< 0.0001), increasing post-transplant infection rate (>10 infections RR 5.11, 1.69-15.5, P = 0.004), and subsequent death from septicaemia (RR 1.6, 1.17-2.18, P = 0.003). Conclusion: PCIR is associated with infection and markers of chronic immunological stimulation but does not independently contribute to inferior renal allograft outcomes, even in ATSI recipients. © 2011 The Authors. Source

Burke M.T.,University of Queensland | Morais C.,University of Queensland | Oliver K.A.,University of Queensland | Lambie D.L.J.,IQ Pathology | And 11 more authors.
American Journal of Clinical Pathology

Objectives: This study aims to investigate how immunosuppression influences the protein expression of antiapoptotic members of the Bcl-2 family - namely, Bcl-xL and Mcl-1 - in nonmelanoma skin cancer (NMSC) and the peritumoral epidermis of renal transplant recipients. Methods: NMSC and peritumoral epidermis protein expression of Bcl-xL and Mcl-1 were assessed by immunohistochemistry in renal transplant recipients receiving tacrolimus or sirolimus and the general population not receiving immunosuppression. Results: NMSC from renal transplant recipients compared with patients not receiving immunosuppressant medications had a reduced Bcl-xL expression intensity (P = .042). Mcl-1 expression intensity in NMSC was decreased in tacrolimus-treated patients compared with sirolimus-treated patients and the nonimmunosuppressed population (P = .024). Bcl-xL expression intensity was increased in peritumoral epidermis compared with NMSC (P = .002). Conclusions: It was shown for the first time that Bcl-xL and Mcl-1 expression are widespread in the peritumoral epidermis and NMSC of renal transplant recipients. Importantly in NMSC, Bcl-xL expression was reduced with immunosuppression exposure, and Mcl-1 expression was reduced in tacrolimus-treated compared with sirolimus-treated patients. © American Society for Clinical Pathology. Source

Rogers N.M.,Central Northern Adelaide Renal and Transplantation Services | Rogers N.M.,Basil Hetzel Institute | Rogers N.M.,University of Adelaide | Eng H.S.,Red Cross | And 13 more authors.
Transplant International

Desensitization protocols reduce donor-specific anti-HLA antibodies (DSA) and enable renal transplantation in patients with a positive complement-dependent cytotoxic cross-match (CDC-CXM). The effect of this treatment on protective antibody and immunoglobulin levels is unknown. Thirteen patients with end-stage renal disease, DSA and positive CDC-CXM underwent desensitization. Sera collected pre- and post-transplantation were analysed for anti-tetanus and anti-pneumococcal antibodies, total immunoglobulin (Ig) levels and IgG subclasses and were compared to healthy controls and contemporaneous renal transplant recipients treated with standard immunosuppression alone. Ten patients developed negative CDC-CXM and enzyme-linked immunosorbent assay (ELISA) and underwent successful transplantation. Eight recipients achieved good graft function without antibody-mediated or late rejection, BK virus or cytomegalovirus infection. One patient had primary non-function due to recurrent oxalosis, and one patient with immediate graft function died from septicaemia. Seven recipients required post-operative transfusion and three developed septicaemia. DSA remained negative by ELISA at 12 months, but were detectable by Luminex®. Anti-tetanus and anti-pneumococcal antibodies, total Ig and IgG subclasses were below the normal range but comparable to levels in renal transplant recipients who had not undergone desensitization. Desensitization protocols effectively reduce DSA and allow successful transplantation. Post-operative bleeding and short-term infectious risk is increased. Protective antibody and serum immunoglobulin levels are relatively preserved. © 2010 European Society for Organ Transplantation. Source

Mohanasundaram D.,Central Northern Adelaide Renal and Transplantation Services | Mohanasundaram D.,University of Adelaide | Drogemuller C.,Central Northern Adelaide Renal and Transplantation Services | Drogemuller C.,University of Adelaide | And 15 more authors.
General and Comparative Endocrinology

The New world primates (NWP) Callithrix jacchus separated from man approximately 50. million years ago and is a potential alternative small non-human primate model for diabetes research. Ultrastructure, and gene expression of pancreatic islets and the recently described diabetes auto antigenic zinc transporters families in human, NWP and pig pancreas were studied. Morphologically NWP islets were larger than pig islets and similar in size to human islets. NWP islets alpha cells had high dense core surrounded by a limiting membrane, beta cells by the mixed morphology of the granule core, and delta cells by moderate opaque core. Antibody staining for insulin, glucagon, somatostatin and Glucagon-like peptide-1 (GLP-1) showed that the distribution pattern of the different cell types within islets was comparable to pig and human islets. In all three species protein expression of zinc transporter ZnT8 was detected in most of the insulin producing beta cells whereas Zip14 expression was widely expressed in alpha and beta cells. In both human and NWP little or no expression of Glut2 was observed compared to Glut1 and glucokinase at the protein level, however the messenger RNA level of Glut2 was greater than Glut1 and glucokinase. In contrast all three glucose transporters were expressed in pig islets at the protein level. The expression of Zip14 in islets is reported for the first time. In conclusion NWP pancreatic islets express comparable islet cell types and distribution to humans and pigs. Importantly, marmosets have a similar glucose transporter profile to humans, making this non-endangered primate species a useful animal model for pancreatic biology. © 2011. Source

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