Along this line, it was interesting that inflammatory Th17 differ

Along this line, it was interesting that inflammatory Th17 differentiation was intact, if not enhanced, in the absence of γc which, however, can be explained by the negative effect of IL-2 signaling on IL-17 expression. Of note, because Pim1TgγcKO mice lack FoxP3+ Treg cells and since Pim1TgγcKO CD4+ T cells could be induced to differentiate into inflammatory T cells, it was surprising that we did not find any signs of autoimmunity in Pim1TgγcKO mice. The in vivo immune response of these mice is currently under

investigation. Collectively, the present study establishes prosurvival effects as the only factor downstream PI3K Inhibitor Library chemical structure of γc signaling that is required for CD4+ T-cell development. Such characteristics set these cells apart from other T-lineage cells that presumably also require lineage specification signals downstream of γc signaling. We expect that further functional studies of γc-deficient CD4+ T cells, together with genetic reconstitution of other select γc downstream

pathways, such as constitutively active Akt or STAT5, will help decipher the detailed molecular pathways in T-lineage cell development and maintenance. CD45.1+ or CD45.2+ C57BL/6 and γc-deficient mice were obtained from the Jackson Laboratory. Human Bcl-2 transgenic mice were provided by Dr. Alfred Singer (National Cancer Institute, Bethesda, MD, USA) [48]. Pim1 transgenic mice have been described [18], and were provided by Dr. Anton Berns (The Netherlands Cancer Institute, Amsterdam, The Netherlands). Animal experiments phosphatase inhibitor library were approved by the National Cancer Institute Animal Care and Use Committee, and all mice were cared for in accordance with National Institutes of Health guidelines. Cells were stained and analyzed on LSRII, ARIAII, or FACSCalibur flow cytometers (Becton Dickinson). Dead cells were excluded by forward

light scatter gating and propidium iodide staining. Antibodies with the following specificities were used for staining: CD8β, CD44, HSA, IL-7Rα, FoxP3, Ki-67 (eBioscience); CD4, CD8α, TCR-β, CD103, γc, human CD3, IL-4, IL-17 (Becton Dickinson); γδ TCR, IFN-γ (Biolegend). For intracellular cytokine staining, in vitro differentiated cells were restimulated for 3 h with PMA and ionomycin with the addition of brefeldin A (eBioscience). Cells N-acetylglucosamine-1-phosphate transferase were fixed and permeabilized with IC fixation buffer (eBioscience). For nuclear FoxP3 staining, cells were first surface stained and then fixed and permeabilized using FoxP3 intracellular staining buffer set according to the manufacturer’s instructions (eBioscience). Active caspase-3 was assayed using a CaspGLOW active caspase-3 kit following the manufacturer’s instructions (eBioscience). Intestines were harvested and washed using 2% FBS in HBSS. After slicing into smaller pieces, intestines were washed using 2% FBS in HBSS and stirred for 20 min at 37°C in 10% FBS in HBSS with 1 mM DTT.

Given the impaired

regulation of antigen presentation and

Given the impaired

regulation of antigen presentation and T-cell proliferation in the absence of CD37 in vitro, one might predict an exaggeration of in vivo adaptive cellular immunity in CD37−/− mice. However, CD37−/− mice show no increased susceptibility to autoimmune induction and conversely, when combined with Tssc6 (Tspan32) deficiency, showed increased susceptibility to the mouse malarial parasite Plasmodium yoelii and poor antigen-specific T-cell responses to influenza infection [16]. It is clear from these findings that data derived in vitro are not predictive of the role of CD37 in immune responses INCB024360 mw in vivo. In this study we examined the role of CD37 in in vivo adaptive cellular immune responses. CD37−/− mice were challenged with live and irradiated tumors, and soluble antigens coupled to the membrane-translocating peptide penetratin — all immunogens known to elicit powerful IFN-γ T-cell responses in WT mice. We show that CD37−/− mice make poor CD4+ and CD8+ T-cell IFN-γ responses to both tumor and model antigen challenge. Furthermore, we present evidence that CD37 ablation impairs various aspects of DC function including cell migration and adhesion. This study demonstrates that a defect in DC migration is a major cellular impairment that underlies poor cell-mediated and anti-tumor responses in CD37−/− mice. Studies of pathogen resistance

Acalabrutinib molecular weight in CD37−/− mice suggested a role for CD37 during development of antigen-specific T-cell responses [16]. Since antigen-specific effector T cells are a critical requirement for tumor elimination [17], rejection of a syngeneic lymphoma-derived cell line transfected with the human cancer antigen Mucin 1 (RMA-Muc1) was compared between WT and CD37−/− mice. While RMA cells grow unchecked in mice of a C57BL/6 (WT) background (Fig. 1A), RMA-Muc1 cells provoke antigen-specific

T-cell responses and tumor rejection typically within 2 weeks [18]. However, CD37−/− Carnitine palmitoyltransferase II mice challenged with RMA-Muc1 failed to reject these tumors over a similar time course (Fig. 1B). Similarly, when challenged with fewer RMA-Muc1 cells, tumors grew significantly larger in CD37−/− mice than in their WT counterparts (Fig. 1C), indicating a role for CD37 in antitumor responses. To compare development of antitumor T-cell responses in WT and CD37−/− mice, γ-irradiated RMA-Muc1 cells were injected i.d. and ELISPOT analyses performed 2 weeks later. While overall splenocyte numbers and leucocyte population frequencies did not differ between WT and CD37−/− mice (Supporting Information Fig. 1), the frequency of Muc1-specific IFN-γ-producing T cells induced in CD37−/− mice was significantly lower than that of WT mice (Fig. 2A), correlating with increased tumor growth observed in CD37−/− mice after RMA-Muc1 tumor challenge (Fig. 1).

Therefore, a role of non-cellular components in the epidermal ant

Therefore, a role of non-cellular components in the epidermal antifungal defence was suggested. To investigate the presence of such factors in these infections, the expression of human beta defensins 2 and 3 (hBD-2, hBD-3), RNase 7, psoriasin, toll-like receptors 2, 4 and 9 (TLR2, TLR4

and TLR9) and dectin 2 was analysed by use of immunostainings in skin biopsies. We found that hBD2, hBD3, psoriasin, see more RNase7, TLR2 and TLR4 were significantly more often expressed in distinct layers of lesional epidermis as compared with uninfected epidermis. In both infections but not in normal skin, hBD2 and hBD3 were commonly expressed within the stratum corneum and in the stratum granulosum. Similarly, psoriasin was seen more often in the upper skin layers of both infections as compared with normal skin. No significant differences between normal and infected skin were found for

the expression of TLR9 and dectin 2. Our findings clearly show Dorsomorphin nmr the expression of specific antimicrobial proteins and defence-related ligands in superficial tinea as well as in pityriasis versicolor, suggesting that these factors contribute to fungal containment. “
“Although the consequences of invasive fungal infections (IFIs) secondary to chronic hepatitis B infections secondary IFIs are serious, the incidence and main pathogenic factors of IFIs in acute-on-chronic liver failure (ACLF) patients remain unclear. This study included 1200 Vasopressin Receptor hepatitis B patients who were treated in the Department of Infectious Diseases, Shanghai Changzheng Hospital from January 2006 to January 2009. Patients with ACLF were screened according to the diagnostic guidelines for liver failure. Patients with ACLF and secondary IFI were the disease group, and patients with ACLF without secondary IFI were the controls. The incidence of IFI, mortality, and possible IFI causes in two groups

were evaluated retrospectively. Sixty patients with ACLF had secondary IFI, of which 14 were confirmed cases and 46 were suspected cases. The incidence of IFI was 47.62% for ACLF patients. Logistic regression analysis showed that the level of hepatitis B viral (HBV) DNA was an important risk factor for secondary IFI in ACLF patients. Receiver operating characteristic curve analysis suggested that when the number of HBV DNA copies was higher than 3.16 × 103 copies ml−1, the possibility of secondary IFI in ACLF patients increased significantly, while white blood cell levels showed protective effects for these patients. The incidence of IFI is high in ACLF patients and high hepatitis B virus DNA levels may be an independent risk factor of secondary IFI in these patients. “
“A total of 165 sporotrichosis cases occurring in Nagasaki prefecture, and examined at Nagasaki University Hospital, were evaluated.

Ching and colleagues have developed a rapid immunochromatographic

Ching and colleagues have developed a rapid immunochromatographic flow test to detect the anti-O. tsutsugamushi IgG and IgM in patients’ sera for diagnosis of scrub typhus, by employing a Karp r56 protein that contained deletions of 79 and 77 amino acid residues at the N and C terminals, respectively, as the diagnostic antigen (19, 20). Antibodies prepared from serum of patients with scrub typhus tend to recognize this protein in general. Mice immunized with the 56-kDa protein generated neutralizing antibodies and showed increased resistance to homologous O. tsutsugamushi infection (21). These data suggest that it is a favorable diagnostic antigen and

vaccine candidate. In this report, we describe the this website molecular cloning, expression and purification of the 56-kDa protein from O. tsutsugamushi strain Karp and investigate the immunogenicity of the recombinant protein. Primers were designed based on the check details published 56-kDa gene nucleotide sequence (GenBank accession no. M33004.1). The upstream and downstream primers were designed to contain NcoI and XhoI restriction sites, respectively: Ot56-F

(positions 298–316), 5′-AGACCATGGCTCAGGTTGAAGAAGGTA-3′; and Ot56-R (positions 1386–1404), 5′-GTCTCGAGCTAAGTATAAGCTAACCCT-3′. Genomic DNA isolated from O. tsutsugamushi strain Karp was used as a template. PCR was performed in a final volume of 50 μL containing approximately 50 ng DNA, 200 μM each deoxyribonucleotide triphosphate, 10 pmol each primer, 5 μL of 10 × PCR buffer (Mg2+ Plus; TaKaRa Biotechnology, Dalian, China) see more and 0.5 U of Ex-Taq DNA polymerase (Takara Biotechnology). Thermal cycling conditions were as follows: 2 min at 95°C, 2 min at 95°C, followed by 30 cycles of 30 s at 94°C, 30 s at 57°C and 1 min at 72°C. A final step of 10 min at 72°C was added to the last cycle. PCR products were analyzed by 1% agarose gel electrophoresis. pET30a(+) and purified PCR products were digested with restriction enzymes NcoI and XhoI (TaKaRa Biotechnology), then ligated overnight at

16°C. The ligation mixture was initially introduced into E. coli DH5α. The recombinant plasmids were identified by PCR, enzyme digestion and were confirmed by sequencing. The plasmid construct was then transformed into E. coli Rossetta (Novagen, Madison, WI, USA) for expression. Escherichia coli Rossetta containing the appropriate plasmid was cultured at 37°C in LB broth containing kanamycin and chloramphenicol. Cultures were induced at an OD600 of 0.6–0.7 with IPTG to a final concentration of 1 mM, and grown for a further 5 hrs. Cells were then pelleted and resuspended in 50 mM phosphate buffer (pH 7.4). After cell lysis by sonication, cellular debris were eliminated by centrifugation at 8000 g for 15 min at 4°C. The water-soluble fraction of the lysate was collected for purification, as described below. To purify the recombinant protein, the cell lysate, containing protein with six His tags, was filtered through a 0.

RAW cells were treated with 20 ng mL−1 of murine recombinant TNF-

RAW cells were treated with 20 ng mL−1 of murine recombinant TNF-α and RCAN-1 levels were assessed 1.5, 4, and 8 h later. As shown in Fig. 6, RCAN1-4 was increased modestly, but these increases did not reach statistical significance and are therefore unlikely to contribute much, if at all, to the inductions observed learn more in Figs 1–5. The above data, as well as previous studies implicating RCAN1 in T-lymphocyte function (Rothermel et al., 2000; Narayan et al., 2005), suggest that RCAN1 plays an important overall role in immune function. In order to better determine the functional significance of RCAN1 in the macrophage and immune

response, we carried out in vivo infection analyses on RCAN1 KOs and WT controls. The animals used for these studies have been described previously (Ryeom et al.,

2003), and have a portion of these C-terminus coding region removed, leading to the total loss of expression of both major RCAN1 isoforms. KO and WT mice were nasally infected with 10 000 CFU of the gram-negative bacteria F. tularensis. After 7 days, the mice were sacrificed and the bacterial burden and proinflammatory cytokine levels were assessed in the lung (the main target of intranasally administered F. tularensis) and spleen. As shown in Fig. 7, no statistically significant change in bacterial burden was observed in the 7-day KO lung as compared with the WT when using a using a two-tailed Mann–Whitney test (note: significance was observed using a one-tailed Mann–Whitney test, but because the two-tailed test is a more stringent comparison, we have chosen to use these results). Spleen

bacterial see more burden was also assessed, with much lower bacterial numbers observed and no differences found between KO and WT (data not shown). NFAT proteins are major transcription factors critical for the immune response, especially in the induction of cytokine genes such as IL-2, why IL-4, IL-6, IFN-γ, and TNF-α (Rao et al., 1997; Crabtree, 1999; Rusnak & Mertz, 2000; Kiani et al., 2001; Peng et al., 2001; Crabtree & Olson, 2002; Ryeom et al., 2003). Because NFATs are tightly regulated by calcineurin and RCAN1 regulates calcineurin, it is reasonable to assume that RCAN1 may regulate calcineurin-dependent cytokine production. To assess this in vivo, KO and WT mice were nasally infected with 10 000 CFU of F. tularensis, and then evaluated for inflammatory cytokine levels in the lung and spleen 7 days after infection. As expected, a strong elevation in all of the proinflammatory cytokines examined, including MCP-1, IL-6, IFN-γ, and TNF-α, was observed in F. tularensis-infected vs. noninfected mice (N=6–7 for infected; N=2 for noninfected controls). Importantly, a statistically significant increase in all the tested F. tularensis-infected KO mice cytokine levels was observed in the lung as compared with F. tularensis-infected WT mice cytokines (Fig. 8).

The data indicate that LPG and L mexicana parasites exert opposi

The data indicate that LPG and L. mexicana parasites exert opposing effects on PKCα activity of susceptible and resistant mouse macrophages, which correlate with the magnitude of burst oxidation and with the survival of the parasites within macrophages. Taken together, our data suggest that PKCα plays an important role in the L. mexicana infection outcome in vitro. One of the primary defence mechanisms of macrophages against Leishmania infections is the oxidative metabolism. It has been shown that L. donovani Dabrafenib parasites avoid triggering the oxidative burst by actively inhibiting

PKC in macrophages (30), and the molecule responsible of this inhibition is LPG (20). LPG is a

glycosylinositolphospholipid (GPI)-anchored polymer formed by repeating disaccharide-phosphate units, through which promastigotes interact with both the insect vector and the mammalian host. LPG is essential for infecting macrophages through various mechanisms. It has been shown that LPG alters the organization of lipid microdomains on the phagosome membrane. Additionally, LPG participates in other immune evasion mechanisms such as the efficient of scavenging toxic oxygen metabolites, modulation of inducible nitric oxide synthase (iNOS) and downregulation of PKC activation, required for the assembly of the NADPH oxidase complex (31,32). It has been proposed that Selleck Torin 1 a fraction of LPG intercolates from the lipid bilayer of the parasite to the lipid bilayer of the macrophage (33). PKCα, which is rapidly recruited to the nascent phagosome, is the predominant isoenzyme required for the O2− production and additionally regulates other macrophage functions related to host defence, such as FcγR-mediated phagocytosis and signal transduction leading to activation of ERK1/2 (14,34,35). PKCα is associated with the phagosomal membrane and phosphorylates the

myristoylated alanine-rich C kinase substrate (MARCKS), Carbohydrate a membrane protein associated with actin-based motility and with membrane trafficking. PKC-dependent phosphorylation of phagosome MARCKS leads to the movement of both lysosomes and phagosomes on microtubules, that is required for their interaction. In the J774 cell line, it has been demonstrated that the inhibition of PKCα by L. donovani LPG leads to the inhibition of F-actin depolymerization at the phagosomal membrane, thereby avoiding the fusion events required for the delivery of endosomal contents into parasitophorous vacuoles, thus permitting parasite multiplication (35–37). In this work, we analysed if the modulation of PKCα by LPG of L. mexicana was related to parasite survival in macrophages of susceptible BALB/c mice vs. cells of the more resistant C57BL/6 mice. We found that L.

[57] A Vβ2-containing ternary complex includes even more CDR3β–CD

[57] A Vβ2-containing ternary complex includes even more CDR3β–CD1d contacts.[56] How can an invariant receptor such as the iNKT TCR show promiscuity in antigen recognition? There is limited polymorphism at position 93 of the Vα24-Jα18 chain,[58] but the major variable region of the iNKT TCR is the CDR3β loop. Evidence suggests that contact between CDR3β and CD1d mitigates the energetic penalty of binding a lower affinity CD1d–ligand complex. Structures of an iNKT TCR with varied ligands clearly show that weaker ligands require more contribution from CDR3β at the TCR–CD1d interface.[54] Mutagenesis studies also

support this conclusion.[50, 59] Naturally occurring CDR3β sequence variants PD-1 inhibitor confer a range of CD1d–ligand affinities on the

iNKT TCR. All iNKT TCRs recognize high-affinity ligands such as αGalCer, yet reduced numbers interact with weaker agonists.[60, 61] Invariant NKT-cell clones show bright, homogeneous staining with αGalCer–CD1d tetramers Sunitinib research buy but when tetramers loaded with the weaker agonist OCH are used, stain as OCH–CD1d tetramer bright, intermediate or dim.[60] The staining pattern observed for OCH–CD1d tetramers matches that for β-glycosylceramide–CD1d tetramers, and the hierarchy was confirmed by surface plasmon resonance analysis of the interaction between cloned TCRs and ligand–CD1d. The CDR3β affinity hierarchy, applicable to diverse GSL antigens, is therefore not indicative of antigen preference by different iNKT TCRs, but is a function of CDR3β sequence. Interestingly, the iNKT-cell repertoire may be selected to exclude cells with high

autoreactivity.[62] Mallevaey et al.[62] modified the CDR3β of a naturally occurring iNKT TCR to create an extra-sticky variant that made additional hydrophobic contacts with αGalCer–CD1d from the CDR3β loop. Only appropriate iNKT cells engage in an NKT response: exposure of mouse iNKT cells to weak antigen leads to enrichment for Vβ7-expressing clones (which Niclosamide use more CDR3β–CD1d contacts) with each cell division cycle, whereas αGalCer, able to engage all iNKT cells, induces no bias.[63] Together, these studies suggest that the iNKT repertoire is selected to fall within a delimited window of affinity for ligand–CD1d, yielding a gamut of iNKT cells of fixed reactivity. Hence, like T cells, not all iNKT cells respond to all antigens; clonal expansion of a specific population ensures an appropriate response. Unlike TCR–pMHC complexes,[64] iNKT TCR–antigen–CD1d ternary complex formation depends upon induced fit of CD1d and antigen to a rigid TCR.[52, 65] Consistently, the antigen–CD1d surface is moulded to resemble the topology of αGalCer–CD1d in the iNKT TCR–αGalCer–CD1d complex. Analysis of αGalCer variants demonstrates the importance of conserved contacts between the galactosyl headgroup and the iNKT TCR.[63, 66] Borrelia burgdorferi αGalDAG has its headgroup repositioned upon binding iNKT TCR,[67] as does S. pneumoniae-derived Glc-DAG-s2.

01) Ub fusion DNA vaccine enhanced the cytotoxic T cell response

01). Ub fusion DNA vaccine enhanced the cytotoxic T cell response,

compared with Ag85A DNA inoculation (P < 0.05). The blank vector or pcDNA3-ub immunization did not induce CTL response. The spontaneous release was below 10%. It has been reported that DNA vaccines preferentially induced Th1-dominant immune response. The exact mechanism of driving Th1- or Th2-type response has not been well known, but it has been suggested that CpG motifs from a bacterial plasmid might be responsible for driving immune responses towards Th1 type. Th1-type response has been reported to correlate with protective immunity in certain tumour, bacterial or viral infection, as well as some parasitic disease. Protective immunity against tuberculosis mainly depends

Crizotinib on cellular immune responses and some cytokines of Th1 type, such as IFN-γ. Hence, to improve the DNA vaccines against Mycobacterium see more tuberculosis, some strategies must be explored to enhance the protective immune response. In our study, we chose ub to modulate the immune response elicited by Ag85A DNA vaccine. It is well known that ub–proteasome pathway is the main source for intracellular protein turnover. MHC class I most often presents peptides derived from endogenously synthesized proteins, which are degraded by the proteasome. Hence, higher rates of intracellular antigen turnover should increase the number and variety of fragments and peptides available for MHC I binding, which may result in an increase in cell-mediated response to the expressed antigens. To this point, conjugation of the antigen with ub should target the endogenously synthesized antigens to the proteasome pathway and result in an enhanced cellular immune response. Some researchers have optimized the efficacy of DNA vaccines by increasing the antigen degradation [22–25]. There are two methods of fusing the ub with the interest protein. One is to mutate the C-terminal residue of Ub from glycine Erastin in vitro (G) to alanine (A), resulting in a stable ub-protein (UbAAg). This stable ub-protein can be polyubiquitinated and degraded quickly by the proteasome. The other method

is to add an arginine (R) to the C-terminus of ub, resulting in an unstable ub-protein (UbGR-Ag). This fusion protein can be quickly recognized and degraded by the ub system according to the N-end rule, also resulting in promoted protein degradation. Based on the ub paradigm, we fused UbGR with Ag85A antigen from M.TB in our study. The change in the immune response elicited by UbGR-Ag85A fusion DNA vaccine indirectly showed the change in Ag85A degradation. Compared with the Ag85A DNA immunization, UbGR-Ag85A fusion DNA vaccine resulted in an lower antibody IgG, an enhanced lymphocytes proliferation, a stronger Th1-type immune response and an enhanced cytotoxicity of CTL. To generate a protective immune response against infection by Mtb, CD4+ and also CD8+ T cell responses are essential.

1 g greater LVMI (95% CI 0 5–1 6) 118 However, analysis of the NH

1 g greater LVMI (95% CI 0.5–1.6).118 However, analysis of the NHANES III data did not show any association between high dietary phosphate intake and mortality in 1105 CKD patients (HR 0.98 per 100 mg/dL increase (95% CI 0.93–1.03)).119

Few clinical trials have looked at lowering dietary phosphate absorption in participants with normal phosphate levels to prevent the complications of CKD-MBD. An experimental study using a rat model of CKD-MBD reported animals with reduced GFR fed a grain-based diet, see more compared with standard synthetic casein animal diets, had lower serum phosphate, urinary phosphate excretion and serum levels of FGF-23.120 The same investigators conducted a cross-over trial in nine patients (mean eGFR 32 mL/min) and compared vegetarian and meat diets. They reported decreased urine phosphate excretion, lower serum phosphate and decreased FGF-23 levels with a vegetarian diet

after 1 week.121 This study also highlighted that higher dietary phosphate intake was associated with increased FGF-23. Dietary phosphate counselling for CKD patients can be complex and patients are often confused by the multitude of recommendations. Simplifying the approach by asking them to eat more grains and less meat and less pre-prepared or packaged foods may potentially lead to increased dietary adherence and subsequent improved phosphate homeostasis. One study educating ESKD patients on dialysis to avoid phosphate-containing food additives resulted in modest improvements in hyperphosphataemia.122 However, further dietary studies are required in CKD patients as additives are increasingly being added PI3K inhibitor to processed and fast foods and the effect of dietary modifications on serum phosphate levels in early CKD is unclear. Despite the rapidly growing body of literature suggesting phosphate dysregulation is associated with increased morbidity and mortality in CKD, what remains to be established is whether early intervention

to prevent phosphate retention can impact on the development of the adverse clinical outcomes associated with CKD-MBD. To date, there has not been an adequately powered, placebo-controlled, multicentre RCT evaluating Dipeptidyl peptidase the effects of phosphate-lowering therapy on reduction of CVD burden in CKD patients. One of the first questions to help design an RCT addressing phosphate homeostasis in early CKD would be to determine the trigger for intervention or the abnormality that one should aim to correct. Hyperphosphataemia occurs late in CKD, at which point arterial or ventricular function may be impaired, so the approach should probably be to intervene before this occurs. Rising phosphate levels within the normal range maybe both a trigger for intervention and its target, but phosphate levels undergo circadian and dietary variation and fasting levels may also be uninformative, so this approach may not prove valuable.

Results: Twenty-three studies (n≥4675 respondents) were included

Results: Twenty-three studies (n≥4675 respondents) were included. The studies were conducted in the United Kingdom, United States, Australia, Sweden, Netherlands, and this website Iran. Four (17%) were multinational

studies. Nephrologists’ preferences varied with respect to: medical suitability – some indicated lower likelihood of recommending transplantation for patients with cardiovascular disease, diabetes, obesity, and infection; non-adherence was regarded by some as a contraindication for transplantation; and socio-demographic characteristics – patients of older age, ethnic minorities, or low socio-economic status were less likely to be recommended. Six major themes underpinned nephrologists’ perspectives: prioritising individual benefit and safety, maximising efficiency, patient accountability, justifying gains, protecting unit outcomes, and reluctance to raise patients’ expectations. Conclusions: Variability in nephrologists’ preferences may be contributing to disparities in access to transplantation. Evidence-based guidelines supplemented with pragmatic tools for determining Alvelestat purchase medical and psychosocial criteria for referral and waitlisting may support more systematic and equitable decision-making.

Continuing medical education informed by current evidence on transplant outcomes, and psychosocial and educational interventions, particularly for high-risk or disadvantaged patient populations, could help to reduce overall disparities in access to transplantation. 259 POLYCYSTIC KIDNEY DISEASE AS A RISK FACTOR FOR NEW ONSET DIABETES AFTER RENAL TRANSPLANTATION: A META-ANALYSIS J JANARDAN1, R WALKER2,3 1Department of General Medicine, The Alfred hospital, Melbourne, Victoria; 2Department of Renal Medicine, The Alfred hospital, Rho Melbourne; 3Monash University, Melbourne, Victoria, Australia Aim: A systematic review of published medical literature on autosomal dominant polycystic kidney disease (ADPKD) as a risk factor for new onset diabetes after transplantation

(NODAT) in renal transplant recipients. Background: NODAT is an important complication of renal transplantation with reported rates varying from 3% to 46%, depending on the diagnostic criteria and length of follow-up. There is conflicting data regarding the increased incidence of NODAT in patients with ADPKD. Methods: We searched the PUBMED database for studies published before February 2014. Out of 129 citations, 12 suitable studies were selected for analysis. The incidence of NODAT in patients with ADPKD was compared to patients with alternative renal pathology using odds ratio (OR) and respective 95% confidence interval (CI). Results: The analysis revealed a higher incidence of NODAT in the ADPKD population (OR: 1.15, 95% CI: 1.06–1.25).