RNA analysis indicated that mhuA and mhuB are each transcribed from individual Fur-regulated promoters. GSK-3 activity Moreover, RNA analysis of an mhuB deletion mutant and a promoter reporter assay coupled with β-galactosidase suggested that MhuB could function as an activator for mhuA transcription. Finally, the role of MhuA as the heme/hemoglobin receptor was confirmed by construction of an mhuA deletion mutant and its complemented strain followed by growth assay. Iron is an element integral to the growth of almost all bacteria.

However, the availability of iron for bacteria is limited because it is usually present as insoluble ferric hydroxide polymers in an aerobic environment or bound to iron-binding proteins such as transferrin and lactoferrin in mammalian hosts (1). Therefore, most bacteria have

evolved the ability to acquire iron under iron-restricted conditions. Numerous bacteria produce and secrete siderophores (low-molecular weight iron-binding chelators) which can remove ferric iron from iron-binding proteins. In Gram-negative bacteria, ferric ion complexed with siderophore (ferrisiderophore) is transported into cells via a TonB-dependent specific uptake system, consisting of an outer membrane receptor protein and an ABC transporter (2). In addition, certain bacteria acquire heme as a nutritional iron source by a TonB-dependent system, similar Maraviroc solubility dmso to those for ferrisiderophores, which includes the binding of heme or heme-containing proteins such as hemoglobin to the cell surface receptor, followed by transport of the intact heme moiety into the cell (3). Siderophores are unable to remove the iron from heme. Moreover, when intracellular iron concentrations are high, expression of those systems studied to next date is negatively regulated at the transcriptional level by a global iron-binding repressor protein called Fur (ferric uptake regulation) with ferrous ion as a corepressor, (4, 5). V. mimicus was first described as a group of biochemically atypical strains of V. cholerae

(6) but they share some pathogenic factors such as enterotoxins and hemolysins (7). V. mimicus, like other pathogenic Vibrio species, inhabits environmental water, including river, brackish, and sea water, and causes diarrhea through eating fish and shellfish contaminated with the bacterium (8). The present authors have previously reported that V. mimicus secretes the siderophore aerobactin in response to iron restriction (9), and that the iucABCD genes engage in aerobactin biosynthesis. They have also reported that the ferriaerobactin complex is incorporated into the cytosol via the 77-kDa IROMP, IutA, and the ABC transporter, MatCDB (10). V. mimicus also expresses 80-kDa IROMP under iron-restricted conditions (9). Hence, V. mimicus is expected to use at least one other iron source besides ferriaerobactin. Although many Vibrio species, including V.

, 2005, 2008; Hu & Ehrlich, 2008). Historically, transformation was the first HGT mechanism identified. In 1928, Griffith reported the

‘transformation’ of rough, avirulent live pneumococci into smooth, virulent pneumococci by the addition of factors from dead, smooth, virulent pneumococci (Griffith, 1928). Thus, from its first recognition, transformation was demonstrated to be a population-level virulence factor (Hu & Ehrlich, 2008); however, this very important clinical aspect of Griffith’s seminal work was overshadowed for generations by the even larger basic science implications that derived from this same work. Griffith’s work also suggested the chemical nature of the gene and demonstrated Ibrutinib research buy conclusively that individual genes were not living entities in and of themselves. His observations selleck also supported Mendel’s concept of there being discrete genes associated with specific phenotypes (Mendel, 1866), but from a practical basis, this work provided the means, through purification, to identify the hereditary molecule. In 1944, Avery, McLeod, and McCarty, in a series of follow-up experiments to Griffith’s work demonstrated, to the surprise of the world at that time, that DNA, not protein, was the pneumococcal transforming substance (Avery et al., 1944), and in so doing,

ushered

in the era of mechanistic molecular biology. Competence and transformation are actually two separate molecular processes. Competence is the metabolic state of being able to take up foreign DNA into the cell, and transformation results if and when foreign DNA is integrated into the host chromosome, changing the genotype and ultimately the phenotype of the cell. In most bacterial species in which competence has been studied, it has been determined to be an inducible phenomenon associated with nutrient limitation or part of an SOS response (Herriott et al., 1970; Håvarstein et al., 2006; Kreth et al., 2006; Prudhomme et al., 2006; Claverys & Håvarstein, 2007; Claverys et al., 2007; Thomas et al., 2009). Therefore, these processes, which increase the probability of mutation considerably, BCKDHB are triggered when the bacteria are under stress and indicate that bacteria can control their mutational rate based on environmental conditions. This is in stark contrast to the widely held view of evolution that mutational rates are invariant and are not able to be controlled by the organism. Viewed teleologically, the bacteria ‘realize’ that they must ‘change their spots’ to survive and thus activate an energetic system to increase the likelihood of genetic recombination and genic reassortment.

The defects were located at the ankle (three cases), foot (two cases), and heel (six cases).

Particular attention was paid to precise patient selection and surgical refinements. Patient selection was based on the lower limb vascular status by palpable distal pedal pulses and ankle brachial index ranging from 0.9 to 1.2. Surgical techniques were refined as precisely locating the perforators of peroneal artery, placing the skin paddle in upper third of leg for a distal region coverage, designing a 7-cm-wide adipofascial pedicle with a 2 cm skin paddle on it, preserving the mesentery structure of sural nerve and concomitant artery with or without including gastrocnemius muscles cuff, no tunneling when inset this flap and supercharging GDC-0941 cell line with lesser saphenous vein whenever needed. All the flaps survived completely. Only Rapamycin ic50 one patient required immediate anastomosis of lesser saphenous

vein to local vein around defect in order to relieve the venous congestion during operation. Patients felt diminished but adequate recovery of sense of touch and temperature at the flap. Following the precise patient selection and surgical refinements, the modified reverse sural flap seemed to be a reliable and effective local flap for reconstruction of the soft tissue defects on ankle and foot. © 2013 Wiley Periodicals, Inc. Microsurgery 33:342–349, 2013. “
“Vascular endothelial growth factor (VEGF) induces angiogenesis and osteogenesis in bone allotransplants. We aim to determine whether bone remodeling in VEGF-treated bone allotransplants results from repopulation

with circulation-derived autogenous cells or survival of allogenic transplant-derived cells. Vascularized femoral bone transplants were transplanted from female Dark Agouti rats (DA;RT1a) to male Piebald Viral Glaxo (PVG;RT1c). Arteriovenous bundle implantation and short-term immunosuppression were used to maintain cellular viability. VEGF was encapsulated in biodegradable microspheres and delivered intramedullary in the experimental group (n = 22). In the control group (n = 22), no VEGF was delivered. Rats were sacrificed at 4 or 18 weeks. Laser capture microdissection find more of bone remodeling areas was performed at the inner and outer cortex. Sex-mismatched genes were quantified with reverse transcription-polymerase chain reaction to determine the amount of male cells to total cells, defined as the relative expression ratio (rER). At 4 weeks, rER was significantly higher at the inner cortex in VEGF-treated transplants as compared to untreated transplants (0.622 ± 0.225 vs. 0.362 ± 0.081, P = 0.043). At 4 weeks, the outer cortex in the control group had a significantly higher rER (P = 0.038), whereas in the VEGF group, the inner cortex had a higher rER (P = 0.015). Over time, in the outer cortex the rER significantly increased to 0.634 ± 0.106 at 18 weeks in VEGF-treated rats (P = 0.049). At 18 weeks, the rER was >0.5 at all cortical areas in both groups.

Grace et al. in a review of ANZDATA listed patients starting dialysis between 2000 and 2010 found only 7% of postcodes outside of major Saracatinib cities were in the most advantaged quartile, compared with 54% of postcodes within major cities[9] Gray et al. in a similar review of non-indigenous patients on dialysis on found significant differences in disease burden between major capitals (MC), inner remote (IM), outer remote (OM) and very remote (VR) areas – Figure 2.[10] Patients want to be treated close to where they reside to avoid the cost of travel and dislocation involved in visiting metropolitan based clinics.

The implementation of renal palliative/supportive care services in rural areas requires a different model to metropolitan areas if these patients are to have the same standard of care as those in metropolitan areas. General practitioners and renal physicians tend to refer on the basis of previous personal exposure. Providing specialist renal palliative/supportive

care services will need to involve some on the ground outreach services to gain the trust and respect of the local physicians. Any model will need to enhance contact between palliative care services and local physicians. A ‘move aside while we show you how it is done in the city’ approach is unlikely to be successful. The knowledge base for renal palliative this website care will need to be outsourced to the local physicians, GPs, and palliative care nurses to enhance patient care. Given that it is unlikely that rural units will have specialist renal palliative /supportive expertise on site the DNT committee supports the concept of a hub and spoke model of care to provide equity of service in all rural and remote areas.

This implies that metropolitan palliative care services will have a responsibility to provide outreach services and will need adequate resources. The same model is used to provide transplant services successfully in rural areas and not only allows rural patients to access these services locally but provides up skilling of the local workforce. Developments in information technology such as telemedicine are possible solutions to some of the problems associated with distance and isolation. The current Medicare also rebate for consultations by videoconferencing should promote and compensate set up costs. This can be easily performed with currently available technology including Skype. There is a potential role for web based on going education for rural renal physicians and palliative care physicians in renal supportive care. This could potentially involve cased based scenarios in a chat room environment. A model currently working in the New England Area involves having a local supportive care nurse who is experienced in dialysis assess all patients referred to the service. Referrals can be from nursing colleagues, GPs, allied health workers and renal physicians.

Due to the difficulties of diagnosis, several

authors have analysed risk factors suggestive of invasive candidiasis to identify patients at highest risk. Such patients may be potential candidates for preemptive antifungal therapy before becoming seriously ill. The extent selleckchem of body site colonisation due to Candida species was recognised to be related with consequent invasive disease. The quantification of the colonisation was expressed as the Candida colonisation index. Based on the evaluation of independent risk factors predictive of invasive Candida infections, clinically relevant scores were evaluated in the last decade. Particularly, the Candida score that combines the clinical risk factors preceding surgery, total parenteral nutrition and severe sepsis with Candida multi-site colonisation can be considered a useful bedside scoring system to discern patients with mere Candida colonisation from patients with the

risk of invasive candidiasis in non-neutropaenic Selleckchem PS-341 critically ill patient population. “
“The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in chronic asthma has been reported in various studies. However, no study has systematically evaluated the occurrence of Aspergillus hypersensitivity (AH) and ABPA in acute severe asthma (ASA). The aim of this study was to investigate the occurrence of AH and ABPA in patients with ASA. All patients with ASA admitted to the respiratory intensive care unit (ICU) of this institute underwent a prospective evaluation for ABPA using Aspergillus skin test (AST) as a screening tool. Patients with positive AST were labelled as AH and were further investigated for ABPA. Patients with ASA were compared with historical control group of 755 outpatient bronchial asthma patients

previously reported. Of the 357 ICU admissions, 57 (43 females, 14 males; mean age 43.5 years) patients were admitted with a diagnosis of ASA. The PRKD3 occurrence of AH was 50.9% [95% confidence interval (CI) 38.3–63.4; 29/57 patients] whereas the prevalence of ABPA was 38.6% (95% CI 27.1–51.6; 22/57 patients) in patients with ASA. The occurrence of AH and ABPA was significantly higher in the ASA group compared with the outpatient bronchial asthma group (38.5% and 20.5%, respectively). The prevalence of serological ABPA (ABPA without central bronchiectasis) was also higher in the ASA group compared with the outpatient bronchial asthma group (45.4% vs. 23.9%). The occurrence of AH and ABPA is very high in patients with acute asthma admitted to a respiratory ICU. Furthermore, the occurrence of high percentage of serological ABPA calls for the use of AST as a routine screening tool for ABPA in all patients with acute asthma at discharge. “
“Many studies have described the adherence of Candida albicans to epithelial cells but little is known about Candida parapsilosis adhesion and its role in host cell surface recognition.

70.8% of patients had LDL levels >2.6 mmol/L;

43.8% had triglycerides >2.2 mmol/L; 44.1% had HDL<1 mmol/L despite learn more 48% of the patients being on lipid lowering agents. Microvascular, macrovascular and severe late complications were reported in 39.2%, 9.9% and 12.1% patients respectively. The rates of diabetic complications were cataract 12.9%, microalbuminuria 15.7%, neuropathy symptoms 31.7%, leg amputation 1.2% and history of angina pectoris was 6.6%. The A1chieve Study (2013), was a 24-week, multinational, open-label, observational study of 66,726 diabetics who had begun using biphasic insulin aspart 30, insulin aspart, or insulin detemir in routine clinical care. Participants were enrolled from 28 countries across four continents (Asia, Africa, Europe and South America). Results, Complication rates were high (27.2% had macrovascular complications and 53.5% had microvascular complications), particularly in Russia, and use of vascular disease preventative drugs was lower than expected. Age, BMI, diabetes duration, LDL-C, and SBP were positively associated, and HDL-C negatively associated, with macro- and microvascular complications

(all p < 0.05) (Litwak et al, 2013). These results from the Diabcare Asia 2008 and A1chieve study suggests a worldwide failure to achieve glycaemic targets. A better diabetes management with earlier initiation and optimization of insulin treatment regimens may reduce the prevalence of vascular complications, improve the lives of people with diabetes and reduce the burden on healthcare systems. NAKAGAWA TAKAHIKO1,2, selleck screening library KOSUGI TOMOKI3, LANASPA MIGUEL A.2, ISHIMOTO TAKUJI2,3, NAKAYAMA TAKAHIRO2, JOHNSON RICHARD J2 1TMK project, Kyoto University Graduate School of Medicine, Japan; 2Department of Medicine, Flavopiridol (Alvocidib) University of Colorado Denver, USA; 3Department of Nephrology, Nagoya University Graduate School of Medicine, Japan Recently uric acid has attracted public attention as a potential cause for cardiovascular disease. Our group has been studying the role of uric acid in hypertension

and renal diseases. Both animal models and clinical studies consistently demonstrate that uric acid is positively associated with blood pressure, and pilot studies show that lowering serum uric acid reduces blood pressure in rats and humans. Likewise, a causal role for uric acid in kidney disease is suggested by evidence that lowering uric acid with either allopurinol (a xanthine oxidase inhibitor), or benzbromarone (a uricosuric agent) could slow the progression of renal disease in experimental models. The mechanism by which uric acid may drive hypertension and kidney disease involves the induction of endothelial cell dysfunction and vascular smooth muscle cell activation. A tubular epithelial cell is also a target for uric acid which leads to an inflammatory response with cellular phenotypic change. Likewise, some clinical studies have demonstrated an association of uric acid with the progression of diabetic nephropathy.

Tissues collected during necropsy were

analyzed by IHC for the presence of PCV2 antigen. All pigs were weighed on the day of arrival, vaccination and challenge and at necropsy. The average daily weight gain was calculated before (−28 to 0 dpc), after challenge (0 to 21 dpc), and for the entire study period (−28 to 21 dpc). In addition, all animals were examined daily for signs of illness such as: lethargy, respiratory signs, inappetance and lameness. The pigs were vaccinated at −28 dpc with 2 mL of an experimental live-attenuated chimeric PCV2 vaccine with an ORF2 based on the PCV2a subtype (PCV1-2a) as previously described (37, 39) at a titer of 1.6 × 103 TCID50 per mL.

This is the same titer as was used for the inactivated version of the chimeric PCV2 vaccine (Suvaxyn PCV, Fort Dodge Animal Health). For the IDH inhibitor IM route of vaccination, 2 mL of the experimental PCV1-2a vaccine was injected into the right side of the neck using a 0.7 mm × 25.4 mm needle and a 3 mL syringe. For the PO route of vaccination, each pig was held in an upright position and the experimental vaccine administered by slowly dripping Ibrutinib purchase 2 mL into their mouths using a 3 mL syringe. The volume of vaccine dose for both IM and PO routes (2 mL) was chosen on the basis of what is routinely used and convenient for vaccinating pigs in the field. The PCV2b isolate NC-16845 was propagated on PK-15 cells to produce a virus stock at an infectious dose of 2.5 × 103.0 TCID50 per mL, which was used to challenge the pigs. At dpc 0, each pig in the PCV2-challenged

groups (Table 1) received 1 mL of the virus inoculum IM into the right neck area and 3 mL (1.5 mL per nostril) intranasally by holding the pig in the upright position and administering the inoculum by slowly dripping 1.5 mL into each nostril using a 3 mL syringe. Porcine reproductive and respiratory syndrome virus isolate ATCC VR2385 (44, 45) was propagated on MARC-145 cells to produce an infectious stock with a titer of 1 × 105.0 TCID50 /mL. At dpc 0, each pig in the PRRSV-challenged groups (Table 1) received 2.5 mL of the PRRSV challenge virus inoculum intranasally Glycogen branching enzyme in a similar fashion to that described for PCV2 inoculation. All serum samples from all groups were tested for anti-PCV2-antibodies using the SERELISA PCV2 Ab Mono Blocking kit (Synbiotics Europe, Lyon, France) according to the manufacturers’ instructions. The results were expressed as a SNc ratio, samples being considered negative if the SNc ratio was > 0.50 and positive if it was ≤ 0.50. Serum samples collected at −28, 0 and 21 dpc were tested for the presence of anti-PRRSV antibodies by ELISA (HerdChek PRRS virus antibody test kit 2XR, IDEXX Laboratories).

In the same study, and in contrast to these human ANCA data, F(ab)2 from a murine monoclonal antibody (mAb) had no activating capacity [38]. A PR3- and MPO-ANCA F(ab)2-induced respiratory burst was confirmed in another study [39], but not observed by other investigators [40–42]. The use of human versus murine antibodies, the strength of Afatinib manufacturer the activation response, assaying intra- or extracellular oxidant generation and the antigen specificity of the antibodies that were employed

may, at least in part, explain some of the differences in the results. Williams et al. observed that ANCA F(ab)2 induced p21ras activation that was necessary, but not sufficient, for the respiratory burst [43]. Moreover, gene arrays showed that both ANCA F(ab)2 and ANCA Metformin datasheet immunoglobulin (Ig)G induce leucocyte gene transcription [44]. Interestingly, some of the transcribed genes were unique to intact ANCA IgG and some to the F(ab)2, whereas others were induced by both fragments. Thus, ANCA F(ab)2 bind to the neutrophil and trigger several neutrophil responses that do not depend on FcγR engagement. Few studies investigated this issue in monocytes. Weidner et al. showed that human ANCA also activated respiratory

burst in monocytes and that ANCA F(ab)2 triggered a similar response compared to the complete ANCA IgG [45]. In addition to the antigen-binding fragments, the Fc part of the ANCA molecule is also important. ANCA IgG bind to FcγRIIa (CD32A) and FcγRIIIb (CD16B). FcγRIIa blockade abrogated ANCA-induced activation, whereas the role of the FcγRIIIb blockade is somewhat more controversial [38,40–42,46]. The FcγRIIa has two allelic variants with either a histidine or an arginine at amino acid position 131, resulting

in a high-responder and low-responder receptor form. Neutrophils with the high-responder variant showed a stronger response to anti-PR3 and anti-MPO IgG1 mAbs in vitro[40]. This FcγRIIa also has high affinity to the IgG3 subclass, which is the dominant ANCA subclass in patients with active disease, and had the strongest capability to induce neutrophil adhesion in vitro[47,48]. Kocher et al. observed that ANCA IgG also bind to the FcγRIIIb on neutrophils Cyclooxygenase (COX) that is expressed approximately 10 times higher than the FcγRIIa [46]. Distinct patterns of CD11b increase and CD62L shedding suggested that FcγIIIb is involved in ANCA-induced neutrophil activation. FcγRIIIb has two common genetic variants named NA1 and NA2, the former triggering a stronger neutrophil activation than the latter. A recent study on a large cohort of patients with granulomatosis with polyangiitis (GPA, also known as Wegener’s granulomatosis) demonstrated a similar NA1 allele frequency in patients compared to controls. However, the presence of NA1 was associated with more severe renal disease [49].

The molecular mechanisms through which IRF4 can influence the development of Tc9 and Th9 cells seem to be very similar. Thus,

like in Th9 cells, IRF4 is essential for IL-9 expression in Tc9 cells and binds to the Il9 promoter (author’s unpublished data). Moreover, in Irf4–/– Tc9 cells, the expression of FOXP3 was found to be elevated and retroviral overexpression of FOXP3 suppressed IL-9 production in WT Tc9 cells [63]. Inhibition of IL-9 production by FOXP3 has also been shown in Th9 cells [29]. These data suggest that IRF4 regulates IL-9 production in Tc9 cells both directly via binding to the Il9 promoter and indirectly via affecting Selleckchem PD0325901 FOXP3 expression (Fig. 2) [63]. Tc17 cells are characterized by the production of IL-17 and expression of the Tc17-specific transcriptional program including mRNAs for ROR-γt, RORα, IL-21, and IL-23 receptor (IL-23R) [64, 66, 73]. Tc17 cells have been identified in MS lesions [74]. Likewise, upon immunization with a truncated peptide from myelin oligodendrocyte glycoprotein (MOG37–50), WT mice suffer from EAE accompanied by increased numbers of IL-17-producing CD8+ T cells in the LNs and CNS [66]. By contrast,

Irf4–/– mice have been shown to be resistant to the induction of EAE and failed to develop IL-17-producing CD8+ T cells, illustrating the need for IRF4 not only for Th17-, but also for Tc17-cell differentiation in vivo. Also in vitro, IRF4 was required for the acquisition of the Tc17 phenotype: Irf4–/– CD8+ T cells failed to PD-0332991 in vitro produce IL-17 upon culturing with TGF-β and IL-6 and expressed greatly diminished levels

of mRNAs characteristic of a Tc17-specific transcriptional program. Instead, under Tc17-inducing Paclitaxel conditions, Irf4–/– cells displayed enhanced expression of EOMES and FOXP3, which are master regulators of CTL and CD8+ Treg-cell differentiation, respectively. Forced expression of EOMES and FOXP3 additively inhibited IL-17 production by WT CD8+ T cells, illustrating that the high amounts of these transcription factors contribute to the altered phenotype of Irf4–/– CD8+ T cells. Thus, on the one hand, IRF4 acts as molecular activator of Tc17-cell differentiation by promoting expression of the master regulators ROR-γt and RORα, and on the other hand, IRF4 acts as suppressor of alternative CD8+ T-cell fates by downregulating the expression of EOMES and FOXP3 (Fig. 2) [24]. In addition, our data revealed that MOG37–50-induced EAE is mediated by reciprocal cooperation between IL-17A-producing Tc17 cells and CCR6-expressing Th17 cells [24]. Although WT CD8+ T cells that were transferred into Irf4–/– mice prior to EAE induction developed a Tc17-like phenotype, these cells failed to migrate into the CNS and to induce autoimmune inflammation. Help by CCR6-expressing Th17 cells was required to enable WT Tc17-cell-mediated CNS inflammation.

Based

on the aforementioned literature, finding a higher prevalence in patients with altered TCR Vβ repertoire could be expected. However, several lines of evidence suggest that viral infection and CMV infection in particular were not the main reason for the profound perturbation of the TCR Vβ repertoire observed. First, active inflammatory processes (including viral and bacterial infection) at the inclusion time and episodes of acute rejection were exclusion criteria for the recruitment of patients in the GenHomme cohort. The influence of CMV infectious episodes observed shortly after the transplantation in patients from the GenHomme cohort and thus at distance from the TcL analysis was studied. Similar prevalence of anti-CMV IgG was selleck found in operationally tolerant recipients and patients with chronic humoral YAP-TEAD Inhibitor 1 research buy rejection despite exhibiting dramatically different repertoire usages. Furthermore, in these two groups, no correlation was found between TCR Vβ repertoire usage and CMV serology. Moreover, the analysis of the impact of the CMV pp65-specific T cells on the overall shape of the CD8+ repertoire showed that the TcL typology is not perturbed by CMV pp65-specific clones. Taken together, these data suggest that the TCR classification of the patients cannot be solely related to the CMV response. We then can

hypothesize that such peripheral expansions, and particularly in patients with chronic rejection, could be related to dominant indirect 3 or next direct 30 alloimmune responses against the graft. The role of T cells and especially CD8+ T cells had been likely undermined in the process of chronic rejection, whereas several studies confirmed the presence of CD8+ T cells infiltrate in the graft 31–33. Moreover, we have shown that blood of animals (as reported here in patients) with

chronic rejection exhibited strong alteration of the CD8+ T-cell repertoire 34. The correlation between the Banff score and the shape of the TcL in this study reinforces the hypothesis that CD8+ T cells may be an instrumental player in chronic rejection. As the magnitude of the clonal selection in recipients with chronic rejection correlates with the severity of the rejection, TcL usage could be a useful tool for graft monitoring in these patients. Further studies on sorted Vβ families with strong alteration, on reactivity against donor cells and a long-term follow-up of the stable patient cohort are awaited for improving the interpretation of TCR alteration in long-term graft recipient. Combined with other biomarker data 9–11 and associated with the expression of inflammation or regulatory-related genes (GZMB, T-bet versus FOXP3) as shown, TCR repertoire categorization might be included in the calculation of a “composite score” for the follow-up of patients to prevent rejection or helping to decide upon immunosuppressant withdrawal.