Indeed, microbial exposure in early life may have long-lasting effects into later life, as suggested by an epidemiological association with prevention of diseases such as IBD and

Trametinib asthma [34, 35]. Similarly, delayed colonization of GF mice was shown to result in increased morbidity in experimental models of IBD and allergic asthma [36]. The modulation of epithelial immunity by commensal microorganisms has been unveiled by recent studies (reviewed in [37]). Many mechanisms have been described by which the intestinal microbiota is essential for the full development and function of mucosal immunity. For example, in mammals the full maturation of the gut-associated lymphoid tissues (GALTs) and the recruitment of IgA-secreting plasma cells and activated T cells to mucosal sites has been shown to require microbiota-derived signals acting after birth on both epithelial cells and MAPK Inhibitor Library price DCs [38]. In vertebrates, many products of the commensal microbiota

and of pathogens alike, acting in part on the innate receptors of the TLR and NOD-like receptor families, affect the barrier immunity via pro- and anti-inflammatory mechanisms. The role of TLRs and IL-1 family receptors in controlling the gut microbial ecology has clearly been shown in mice deficient for the common adapter molecules MyD88, in which microbiota-regulated genes have altered expression [39]. MyD88 signaling is required for the epithelial expression of antimicrobial genes, such as Reg3β and Reg3γ, and MyD88 deficiency has been shown to result in an alteration in bacterial composition and diversity [39, 40]. In this review, with only a few exceptions, we focus on the role of bacteria in the regulation of immunity and cancer. However, it is important to remember that, in addition to bacteria, the microbiota is composed of archaea,

fungi, viruses, and bacteriophages, and that dysbiosis is most often associated Avelestat (AZD9668) with changes in the reciprocal composition of the different members of the microbiota. For example, in antibiotics-treated animals, the overgrowth of fungal pathobionts, such as Candida, is often observed [41]. Furthermore, in MyD88-deficient animals raised in conventional facilities, norovirus infection and the reactivation of infectious endogenous retroviruses, such as murine leukemia virus, have been shown to be common occurrences, and result in alterations in innate and adaptive immune responses [39, 42]. With some exceptions, the role of components of the microbiota other than bacteria in regulating immunity and inflammation has received only limited attention, and it is likely that the study of these components will drive some reinterpretation of the mechanisms explaining the role of the microbiota in immunity [41, 43]. Several mechanisms by which different microbial species regulate immunity at different barrier surfaces have been well characterized.

We have previously studied EBV-induced production of IL-6 by CD25+ B cells of healthy individuals and observed no differences compared with CD25– B cells.[44] In the present study we investigated the direct effect of EBV on CD25+ cells in vitro and found that CD25+ B cells of patients with RA have increased immunoglobulin secretion following EBV stimulation. The EBV-induced immunoglobulin production pattern in patients Fulvestrant chemical structure with RA was different compared with the one observed in healthy controls. Patients with RA (n = 7) were good producers of IgG and IgM in CD19+ CD25+ cells. In contrast,

negligible levels of IgG and IgM were measured in cultures of CD19+ CD25+ cells of healthy subjects (n = 2). These findings emphasize that CD25+ B cells of patients with RA may quickly convert into antibody-secreting cells during EBV infection and may contribute to the exacerbation of inflammation in RA patients. Infection with EBV affects the B-cell phenotype in patients with RA by increasing the CD25+ subset and by inducing their immunoglobulin production. These findings clearly link CD25+ B cells to the EBV-dependent sequence of reactions in the pathogenesis of RA. Mikael B

designed the study, performed laboratory work, analysed data and wrote the manuscript. MR performed laboratory work, analysed data and wrote the paper. Maria B designed the study, performed Selleck Compound Library laboratory work, analysed data and wrote the manuscript. This work was supported by grants from the Commission through of European Union (FP7 Health Programme, Gums & Joints no. 261460), the Swedish Medical Research Council (no. 521-2011-2417, no. 521-2008-2199),the Regional Agreement on Medical Training and Clinical Research between the Western Götaland County Council (LUA/ALF), the Ragnar och Torsten Söderberg Foundation, the Medical Society of Gothenburg, the Swedish Association Against Rheumatism, the Gothenburg Association Against Rheumatism, King Gustaf V’s Foundation, the Nanna Swartz Foundation, the AME Wolff Foundation, Rune and Ulla Amlövs Trust,

the Swedish Research Agency for Innovation Systems (VINNOVA/COMBINE), the Swedish Foundation for Strategic Research, the Pharmacist Hedberg Foundation, the Magnus Bergwall Foundation, the Family Thölen and Kristlers Foundation, and the University of Gothenburg. The authors declare no conflicts of interests. “
“The biological behavior of immune cells is determined by their intrinsic properties and interactions with other cell populations within their microenvironment. Several studies have confirmed the existence of tight spatial interactions between mast cells (MCs) and Tregs in different settings. For instance, we have recently identified the functional cross-talk between MCs and Tregs, through the OX40L–OX40 axis, as a new mechanism of reciprocal influence. However, there is scant information regarding the single-cell dynamics of this process.

All patients were either untreated

or treated only with calcium channel blockers. Results: A total of 122 patients, 56 men and 66 women, with EH were enrolled in this study. The average age was 56 ± 12 years old, systolic blood pressure was 144 ± 16 mmHg, HbA1c was 5.6 ± 0.6%, eGFR was 76.9 ± 20.2 ml/min/1.73 m2, serum s(P)RR level was 19.0 ± 4.9 ng/ml, serum prorenin level was 1.27 ± 3.47 ng/ml, PRA was 1.24 ± 1.30 ng/ml/h, and PAC was 141.6 ± 76.9 pg/ml. Single regression analysis showed that eGFR was negatively correlated with s(P)RR (r = −0.337, P < 0.001), but not with prorenin level, PRA, or PAC. Multiple regression analysis of age, systolic blood pressure, HbA1c and s(P)RR levels revealed Panobinostat research buy that age and s(P)RR levels were negatively correlated with eGFR (P < 0.05). Conclusion: These results support the presumption that the tissue RAS is more strongly associated with Kinase Inhibitor Library renal function than the circulating RAS in patients with EH. Moreover, the correlation between the tissue RAS and renal function can be independent of age, blood pressure and HbA1c. WAKUI HIROMICHI, TAMURA KOUICHI, OHSAWA MASATO, KOBAYASHI RYU, UNEDA KAZUSHI, AZUSHIMA KENGO, TOYA YOSHIYUKI, UMEMURA SATOSHI Department of Cardiorenal Medicine, Yokohama City University

Introduction: Angiotensin II (Ang II) type 1 receptor (AT1R)-associated protein (ATRAP) was identified as a specific binding protein of AT1R. We have shown that the ATRAP promotes constitutive internalization of the AT1R and may function as an endogenous inhibitor to prevent pathological activation of the tissue AT1R signaling. The present study was designed to reveal a functional role of renal tubule ATRAP, with a focus on Ang II-dependent hypertension, by employing renal tubule-dominant 3-oxoacyl-(acyl-carrier-protein) reductase ATRAP transgenic mice (ATRAP-TG) and ATRAP deficient mice (ATRAP-KO). Methods: Experiment 1: Wild-type mice (WT) and ATRAP-TG were continuously infused with Ang II and blood pressure (BP) was measured by a radiotelemetric method. Metabolic cage

analysis was performed during the Ang II infusion to evaluate sodium balance. Renal expression of the major sodium transporters was also analyzed. Experiment 2: WT and ATRAP-KO were continuously infused with Ang II. Measurement of telemetric BP, metabolic cage analysis and renal expression analysis of sodium transporters were performed as in Experiment 1. Results: While ATRAP-TG showed a pattern of renal distal tubule-dominant overexpression of ATRAP, ATRAP-KO exhibited no ATRAP expression in all tissues, including renal tubules. At baseline, the telemetric BP of either ATRAP-TG or ATRAP-KO was similar to that of WT. However, in ATRAP-TG compared with WT, the development of hypertension in response to Ang II infusion was significantly suppressed, and the extent of positive sodium balance was significantly reduced during Ang II infusion.

tuberculosis using GenoType Mycobacteria Direct (GTMD) assay targeting 23S rRNA in several EPTB specimens (tissue biopsies, pleural fluid, CSF, urine, etc.), considering combination of BACTEC culture, histological findings and response to ATT, all together as the gold/reference standard. Various PCR tests employed for the diagnosis of EPTB using different gene targets have been summarized in Table 1. TNF-α inhibitor (e.g. inflixmab and etanercept)-induced EPTB has been established in patients with rheumatoid arthritis and Crohn’s disease (Golden & Vikram, 2005; Almadi et al., 2009). The most notable advantage of PCR tests is their rapid turnaround time and reliability for an early detection

of EPTB, which may have

important implications for clinical management and TB control; PD0325901 clinical trial for example, the reliability of PCR to confirm an early diagnosis of TB meningitis and abdominal TB has been well established when smear and culture test are rarely positive (Kulkarni et al., 2011; Galimi et al., 2011). PCR has also been used for an early diagnosis of osteoarticular TB in tissue samples and that can help to start timely ATT (Pandey et al., 2009) and prevent progression to irreversible changes. Cheng et al. (2004) have recommended an early initiation of ATT at least in > 50% cases of their cohort study of 86 patients with EPTB diagnosed by PCR so as to avoid unnecessary mortality and transmission of disease. Similarly, Noussair et al. (2009) have proposed that the PCR results could be used in conjunction with histological findings for the diagnosis of suspected EPTB cases to decide whether presumptive ATT should BMS-354825 molecular weight be continued or discontinued, thereby contributing to decreased costs and decreased potential toxicity related to prolonged unnecessary therapy. There is a major problem of drug resistance in EPTB individuals and particularly in those individuals co-infected with HIV. MDR-TB and XDR-TB (extensively-drug resistant TB) are two crucial forms of drug resistance (Agashe

et al., 2009). The conventional drug susceptibility test takes at least 2 months from Etofibrate the time when the culture is inoculated. RIF resistance is used as a surrogate marker for uncovering MDR as > 90% RIF-resistant isolates are also isoniazid (INH) resistant (Brodie & Schluger, 2009). Eltringham et al. (1999) earlier demonstrated two rapid phenotypic assays for the detection of RIF resistance in M. tuberculosis, that is, the phage-amplified biological assay based on inability of susceptible M. tuberculosis strains to support the replication of bacteriophage D29 in the presence of inhibitory doses of RIF and the RT-PCR assay to demonstrate a reduction in inducible dnaK (Rv0350) mRNA levels in susceptible isolates treated with RIF. The rapid detection of RIF resistance in M. tuberculosis has been meticulously reviewed by Brodie & Schluger (2009) using line probe assays and molecular beacon real-time PCR.

Along with the progression of diabetes and diabetic nephropathy, circulating miR-1179 was gradually increased (2.03 times in DM/N and 2.14 times in DN/DM) , and circulating miR-148b, miR-150 were gradually reduced (2.04 times in DM/N, 2.02 times in DN/DM and 2.03 times in DM/N, 2.02 times in DN/DM respectively). The differentially expressed proteins and the targets of miRNAs induced by high glucose involved in mitochondrial oxidative stress, autophagy and EMT. Ursolic acid and LY294002 inhibited HG-induced mesangial cell

proliferation and decreased ROS generation. The expression of podocin, ZO-1 was down-regulated and the expression of α-SMA was up-regulated in podocyte cultured by high glucose and inhibited by ursolic acid. The cells exposed to HG for 48h showed up-regulated p85PI3K, pAkt, pmTOR and down-regulated LC3BII expression. Ursolic acid down-regulated p85PI3K, p62/SQSTMI, pAkt,

pmTOR and GSK3β Selleckchem AZD1208 expression and up-regulated Wnt5a, LC3BII expression in mesangial cell and podocyte cultured by HG. Mass abnormal mitochondrion and decreased autophagosomes were observed by electron microscopy in cells cultured by HG for 48h and ursolic acid decreased autophagosomes expression. Conclusion: The differentially expressed proteins and the target of miRNAs induced by high glucose involved in mitochondrial oxidative stress, autophagy and epithelial-mesenchymal transition. The over-expression of miR-503 and miR-181d in KKAy mice glomeruli may be responsible for the pathogenesis of DN by regulating the expression of the target proteins, such as heat shock protein 75, GRP75 and GRP78 Ipatasertib solubility dmso et al. The differentially expression of serum miR-1179, miR-148b and miR-150 may be responsible for the pathogenesis of diabetic nephropathy and are potential biomarkers for DN. Ursolic acid can regulate autophagy and EMT and ameliorate high glucose induced podocyte and mesangial cell injury by inhibiting PI3K/AKT/mTOR

pathway, implying that ursolic acid could be a potential treatment for diabetic nephropathy. PRANOTO AGUNG1,2 1Surabaya Diabetes & Nutrition Center; 2Endocrinology Phosphoglycerate kinase Division, Department of Internal Medicine, Dr Soetomo General Hospital, Airlangga University Teaching Hospital, Faculty of Medicine, Airlangga University, Indonesia Diabetes can be found in every country. Without effective prevention and management programs, the burden will continue to increase worldwide. Some 382 million people worldwide, by 2035, some 592 million people, will have diabetes. People with diabetes are at risk of developing a number of disabling and life-threatening complications. Consistently high blood glucose levels can lead to serious diseases affecting the heart and blood vessels, eyes, kidneys, and nerves. People with diabetes are also at increased risk of developing infections (IDF Diabetes Atlas 2013).

Fluorescence microscopy was carried out with a Spot insight camera (model no. 3.1.0; Diagnostic Instruments Inc, Sterling Heights, MI) mounted over an Axiovert S100 microscope (Zeiss, Göttingen, Germany). For image acquisition, Meta Imaging Series 6.1 imaging software (Universal Imaging Corporation, Downington, PA) was used. Lumacaftor clinical trial Cell lysates of 1 × 106 immature DCs were mixed with loading buffer (Roth, Karlsruhe, Germany), heated for 5 min at 95°, and subjected

to SDS-PAGE on a 10% polyacrylamide gel with 0·1% SDS using standard procedures (constant voltage at 200 V; 100 μg protein/lane). Proteins were blotted onto polyvinylidenfluoride membrane (Millipore, Bedford, MA) using a semidry blotting unit (Trans-Blot SD; Bio-Rad, München, Germany) in a Tris/Glycin buffer for 35 min at 2·5 mA/cm2. After transfer, the membrane was blocked in blocking buffer (PBS containing 0·1% Tween-20 and 5% non-fat dry milk powder) overnight at 4°. For detection click here of actin or NF-κB, the membrane was incubated

with horseradish peroxidase (HRP)-conjugated mouse anti-human actin mAb (Santa Cruz Biotechnology) at a dilution of 1 : 2000 in blocking buffer for 2 hr or with mouse anti-human phosphorylated NF-κB p65 mAb (BD Biosciences) at a dilution of 1 : 500 for 2 hr and thereafter with HRP-conjugated goat anti-mouse IgG (Santa Cruz Biotechnology) at a dilution of 1 : 5000 for 90 min. Blots were developed using chemoluminescence (Roti-Lumin; Roth). Student’s t-test was employed to test the statistical significance of the results; P ≤ 0·05 was considered significant. First, we analysed

the internalization of different concentrations O-methylated flavonoid of the FITC-conjugated allergens OVA and AGE-OVA by immature DCs at different time-points. In general, uptake of allergen was increased after application of higher allergen concentrations and time duration. The internalization of FITC-AGE-OVA was significantly enhanced compared with the internalization of FITC-OVA after 1 and 4 hr using the optimal concentration of 10 μg/ml allergen (P ≤ 0·05; Fig. 1a). In order to investigate and characterize the mechanisms of internalization of the allergens OVA and AGE-OVA by immature DCs, inhibitors were used to block the receptor-mediated antigen uptake (mannan and poly I) or to block macropinocytosis (DMA).25–27 All inhibitors were added 30 min before application of the allergen FITC-OVA or FITC-AGE-OVA. Figure 1(a,b) shows that the uptake of allergens was significantly reduced (P ≤ 0·01) by all inhibitors at each examined time-point. The uptake of FITC-OVA and AGE-OVA was completely blocked by mannan, poly I and DMA after 10 min and 1 hr. In the presence of the inhibitor mannan or poly I, FITC-AGE-OVA was taken up at a reduced rate after 4 hr, while the uptake of OVA was still completely blocked (P ≤ 0·05).

In contrast, the control and n-butyrate-treated cultures did not reveal any overall difference in FoxP3EGFP-expressing CD4+ T cells (Fig. 2B). Additionally, FoxP3EGFP-expressing CD4+ T cells were not increased in n-butyrate-treated CD4+ T cells re-stimulated in secondary cultures absent n-butyrate (Fig. 2C). Suppressor activity is a functional readout of Treg cell activity. A further evaluation of potential Treg cell activity assessed the capacity of

the n-butyrate-treated CD4+ T cells to suppress proliferation of responder CD4+ T cells in a co-culture suppression assay (Fig. 3). CD4+ T cells (TEFF) from mitogen-stimulated primary cultures were treated with TGF-β or n-butyrate on Day 0. Following 5 days, living TEFF were co-cultured with mitogen-stimulated CFSE-labelled CD4+ T cells (TRESP) for an additional 3 days at titrations

find more of 2:1, 1:1, 0.5:1 and 0:1 (TEFF:TRESP). The TGF-β-treated TEFF were the only CD4+ T cells from primary cultures that suppressed TRESP proliferation. This suppression was observed at all TEFF:TRESP ratios. In contrast, CD4+ T cells from n-butyrate-treated primary cultures did not suppress TRESP cell proliferation regardless of the TEFF:TRESP ratio. Histone deacetylase inhibitors may prove to be a valuable commodity against unwanted immune responses. This study revealed that n-butyrate anergized mitogen-stimulated CD4+ T cells through blockade of proliferation and IL-2 secretion without enhancement of Treg cell number or function. Defining mechanisms this website by which HDAC inhibitors block T cell function is important in view of their demonstrated ability to protect the host within autoimmune animal models. For example, the benzamide MS-275 attenuated experimental autoimmune neuritis through reduction of rat sciatic nerve demyelination [22]. T cell and B cell infiltration

as well as EAN-mediating pro-inflammatory Dimethyl sulfoxide cytokines IFN-γ and IL-1β were suppressed. The authors observed an increase in FoxP3 mRNA production in lymph nodes and FoxP3+ sciatic nerve-infiltrating cells 1 day after 6 days of daily MS-275 injections. However, it was not tested further if the beneficial effects of MS-275 were exclusively because of an alteration in Treg cell behaviour. MS-275 similarly was shown to inhibit murine contact hypersensitivity induced by dermal exposure to DFNB (2,4-dinitro-1-fluorobenzene) [23]. MS-275 was topically administered daily for either 4 or 6 days concurrently with DNFB exposure. Within 4 days, lymph node cell numbers decreased threefold in MS-275-treated mice. The authors examined the number of FoxP3+ cells within these lymph nodes and found no significant change in expression on Day 4. However, the lymph nodes revealed a twofold increase in FoxP3+ lymph node cells after 6 days of treatment. These results indicated both that MS-275 offered protection from immune responses and that these protective responses might be mediated independent of Treg cells.

BrdU staining was performed with the APC BrdU Flow Kit (BD Biosciences) according to manufacturer’s protocol. Flow cytometric analysis was performed on an LSR II cytometer (BD Bioscience) equipped with the BD FACSDiva software. Post acquisition analyses were conducted using the FlowJo software (Treestar). Total RNA was isolated using the RNeasy Mini Kit (Qiagen) from 6×105 FACS-sorted GFP+ Treg cells, purity >95%, from either 2 WT or 2 OT-II donors per experiment. cDNA templates were synthesized

using SuperScript® II reverse transcriptase (Invitrogen) according to manufacturer’s recommendation. To Selleckchem Doramapimod generate template libraries of rearranged TCR CDR3 regions from Treg-cell cDNA for the Genome Sequencer LY2157299 order FLX System (454 sequencing, Roche), we used primers spanning the variable region between constant Cα and V elements of the Vα8 family (comprising TRAV12-1*01, TRAV12-1*03, TRAV12-1*04, TRAV12-1*05, TRAV12D-2*01, TRAV12D-2*02, TRAV12D-2*03, TRAV12D-2*04, TRAV12D-2*05, TRAV12D-3*01, TRAV12D-3*02, and TRAV12D-3*03). (For primers and PCR conditions please see Supporting Information Table 1.) Forward and reverse primers contained at their 5′ ends the universal adapter sequences and a multiplex identifier (MID) respectively. Amplicons were purified by agarose gel electrophoresis and QIAquick Gel Extraction Kit

(Qiagen), and quantified by Quant-iT™ dsDNA HS Assay Kit (Invitrogen). Single PCR amplicon molecules were immobilized onto DNA Capture Beads within an oil–water emulsion to enable clonal amplification in a second PCR process with universal primers. The emulsion was then disrupted and isolated beads were loaded onto PicoTiterPlates. Sequencing reactions were performed by ultra-deep 454 pyrosequencing on the Genome Sequencer FLX system (Roche Applied Montelukast Sodium Sciences). Productive rearrangements and CDR3α regions were defined by comparing nucleotide sequences to the reference sequences from IMGT®, the international ImMunoGeneTics information system®

(http://www.imgt.org) 33. Rearrangements were analyzed and CDR3α regions were defined using IMGT/HighV-QUEST 57. For transfers of purified cell populations, suspensions from pooled spleens and lymph nodes (inguinal, brachial, axillary, submandibular, and mesenteric) were enriched by magnetic beads (CD4+ T Cell Isolation Kit, MiltenyiBiotec) and subsequently sorted into Foxp3+ and Foxp3− cells by FACS. 4×106 or 2×106 of either Foxp3+ or Foxp3− sorted cells, 1×107 unpurified pLN or mLN cell suspensions, or 1.1×107 enriched CD4+ cells from Foxp3.LuciDTR-4 donors were resuspended in 150 μL PBS and injected into the lateral tail vein of indicated recipient mice. After 9 wk, mice were sacrificed and pLN, mLN, spleen, and the small intestine were taken to recover and analyze transferred Treg cells identified by congenic markers and GFP reporter fluorescence. Mice were imaged 5 min after i.p. injection of 4.

Junctional ectopic tachycardia may be a spectrum of injury to the AV node in which

partial injury may be associated with increased automaticity and more complete injury with AVB. Although to date there has been no report documenting an association between congenital Alvelestat molecular weight junctional ectopic tachycardia in the absence of AVB and maternal autoantibodies, given the lack of symptoms among otherwise healthy women with infants who have complete AVB and/or maternal autoimmune-mediated cardiomyopathy, prospective serological evaluation of the mothers of affected infants should be considered. A spectrum of structural heart disease has been reported among foetuses and infants with maternal autoimmune-mediated cardiovascular disease. In children with maternal autoimmune-mediated ICG-001 cell line congenital AVB, structural congenital heart disease has been reported in 16–42% [22, 38]. These lesions have included persistent ductus arteriosus most of which have required intervention, and atrial and ventricular septal defects. Of greater interest, semilunar and atrioventricular valve abnormalities have also been described in association with AVB, including

stenosis, regurgitation and dysplasia without functional changes (Fig. 4) [22, 38, 54]. Inflammation and fibrosis as well as haemodynamic changes could potentially contribute to the evolution of at least some of these lesions, as suggested in one case of acute chordal rupture with moderate mitral insufficiency in 7-week old infant with echocardiographic evidence of EFE involving left ventricular papillary muscles and chordae [54]. The incidence of structural and even functional heart disease among infants of mothers

with autoantibodies in the absence of AVB is still not certain. In one study that assessed structural abnormalities in a series of 165 pregnancies with autoimmune disease and anti-Ro antibodies, four offspring had structural heart disease suggesting a potential incidence of 2.8%, which represents an increase over that of the general many population [51]. Maternal autoimmune-mediated pathology could be aetiological in the evolution of other forms of congenital heart disease, as suggested in a recent case of prenatally diagnosed hypoplastic left heart syndrome [55]. Further prospective longitudinal investigations of pregnancies (and offspring) in women with anti-Ro and anti-La antibodies with and without autoimmune disease are necessary at this time to determine the true incidence of congenital structural, functional and rhythm-related cardiovascular disease associated with maternal autoantibodies.

Dr Zeevi discusses new diagnostic tools, including the C1q-DSA assay, which detects antibodies that are capable of binding and fixing the first complement protein, C1q [1-3], and can therefore aid in risk stratification Angiogenesis inhibitor of transplant recipients who exhibit DSA. Early detection of DSA and intervention strategies may impact long-term allograft survival. Dr Lefaucheur presents the results of a population-based study of kidney-transplant recipients who were screened for the presence of circulating DSA at the time of transplantation

and at 1 year after transplantation. A risk prediction model that incorporates the ability of DSA to bind complement demonstrates an improved risk stratification process which aids identification of patients at high risk of graft loss, leading potentially to specific and personalized treatment options. The deleterious effects of antibodies to HLA antigens are well known and prohibitive to transplantation. For example, patients with elevated anti-HLA antibodies often wait for extended periods for a compatible organ [4]. Desensitization protocols using IVIg in combination with plasma exchange and/or rituximab have been developed to optimize the availability of compatible donors [5, 6]. Dr Vo discusses data regarding the safety, efficacy

and economic aspects of the current desensitization protocols. Professor Legendre discusses AMR in more detail, and highlights that various phenotypes of acute AMR exist, including subclinical AMR [7], C4d-negative AMR [8], AMR with vascular lesions [9] and AMR without anti-HLA antibodies but with DSA of AZD8055 other origin [10, 11]. These phenotypes vary in severity and potentially

require different treatments, highlighting that accurate diagnosis is essential for effective treatment strategies. In contrast to the role of DSAs and AMR in Metalloexopeptidase allograft survival, Dr Clatworthy discusses the various effects of B cells. There is an appreciation that B cells may play a function in acute cellular rejection and are probably important in rebound AMR after incompatible kidney transplantation. However, aside from the negative effects of B cells and antibody on the allograft, evidence suggests that B cells may have a favourable effect on long-term graft survival, due possibly to the effect of ‘regulatory’ B cells [12-14]. Possible strategies to target B cells are presented. Hypogammaglobulinaemia (HGG) is a known complication of solid organ transplantation and is associated with an increased risk of infection. Monitoring serum immunoglobulin G (IgG) levels before and after transplantation has been proposed as a tool to predict clinical outcomes. Dr Florescu presents the results of a meta-analysis that was performed to evaluate the risk of HGG and its impact on the rate of opportunistic infections during the first year post-transplantation [15].