Role In Rejection Research Articles

Impact of Serum IL 10 on Early Prediction of Allograft Rejection in Liver Transplantation

Abstract Background Tissue transplantation is the preferred treatment for end organ failure such as heart, lung, kidney and liver. Unless the donor and recipient of a transplant are genetically identical, the donated tissue is viewed by the immune system of the recipient as non-self. multiple cytokines are involved in this process, however little is known about their predictive role in rejection. IL10 which exhibit anti-inflammatory activity could be used as early predictor of acute rejection. Objective The aim of the current study is to evaluate the possible association between serum IL10 level in liver transplant patients and acute allograft rejection. Patients and Method: This study was conducted on 45 subjects. Patients will be followed up for 2months and they will be further divided into two groups: Those who developed early acute rejection and those who did not develop rejection (controls) Result The study included 38 patients did not develop rejection and 7 patients developed rejection. We found unchanged during rejection of the LT of the levels of IL-10 Conclusion Several studymust be conducted on cytokines on large sample size to prove early prediction of acute rejection

Scalable, Interfacially Synthesized, Covalent-Organic Framework (COF)-Based Thin-Film Composite (TFC) Hollow Fiber Membranes for Organic Solvent Nanofiltration (OSN).

Covalent organic frameworks have great potential for energy-efficient molecular sieving-based separation. However, it remains challenging to implement COFs as an alternative membrane material due to the lack of a scalable and cost-effective fabrication mechanism. This work depicts a new method for fabricating a scalable in situ COF hollow fiber (HF) membrane by an interfacial polymerization (IP) approach at room temperature. The 2D COF film was constructed on a polyacrylonitrile HF substrate using aldehyde (1,3,5-trimethylphloroglucinol, Tp) and amine (4,4'-azodianiline (Azo) and 4,4',4″-(1,3,5-triazine- 2,4,6-triyl) trianiline (Tta)) as precursors. The COF membrane on the PAN substrate showed 99% rejection of Direct red-80 with remarkable solvent permeance. The rejection analysis revealed that the structural aspects of the solute molecule play a major role in rejection rather than the molecular weight. We further optimized the precursor concentrations to improve the permeation performance of the resulting membrane. The durability study reveals excellent stability of the membrane toward organic solvents. This study also demonstrated the easy scalability of the membrane fabrication approach. The approach was further extrapolated to fabricate a cation-based COF membrane. These charged membranes exhibited an enhanced rejection performance. Finally, this approach can facilitate industrially challenging molecular sieving applications using COF-based membranes.

The role of hyperleptinaemia and low values of interleukin 10 in de novo DSA production after kidney transplantation

BackgroundWhite adipose tissue secretes a number of peptide hormones. The aim of this paper was to determine the role of leptin, adiponectin and interleukin-10 and interleukin-6 on the development of graft rejection in protocol biopsy after kidney transplantation. MethodsIn a prospective analysis (n = 104), we monitored the values of leptin, adiponectin, IL-6, and IL-10 prior to the transplantation and in the 3rd month after the transplantation. The protocol biopsy of the graft was performed in the 3rd month after the transplantation. The group was divided into the following according to the biopsy result: negative result, IFTA 1, borderline, and DSA positive. ResultsAfter adjusting for the differences in the baseline recipient and donor characteristics, we identified the hyperleptinaemia baseline (HR = 2.0444, P = 0.0341) and month 3 (HR = 49.8043, P < 0.0001) as independent risk factors for borderline changes in the protocol biopsy. The hyperleptinaemia baseline (HR = 7.4979, P = 0.0071) and month 3 (HR = 9.7432, P = 0.0057) are independent risk factors for de novo DSA positivity. A low value of IL-10 month 3 is a risk factor for de novo DSA positivity (HR = 3.0746, P = 0.0388). ConclusionsHigher leptin levels and low values of IL-10 might play a role in rejection and de novo DSA production.

Impact of serum IL 10 on prediction of early allograft rejection in liver transplantation

Tissue transplantation is the preferred treatment for end organ failure such as heart, lung, kidney, and liver. The immune system recognizes the transplant as non self if the donor and recipient are not genetically identical. Multiple cytokines are involved in this process; however, little is known about their predictive role in rejection. Interleukin 10 (IL-10) which exhibits anti-inflammatory activity could be used as early predictor of acute rejection. The current study intended to determine any potential relationship between acute allograft rejection and blood IL-10 levels in liver transplant (LT) recipients. This study included 45 patients with cirrhotic liver diseases planned for transplantation. Patients were followed up for 2 months and then divided into two groups: patients who developed early acute rejection and those who did not develop rejection (as controls). Of the study patients, 38 (84.4%) patients did not develop rejection and 7 (15.6%) patients developed rejection. The levels of IL-10 did not change during rejection of the LT. In conclusion, the findings of the current study indicated no relation of IL-10 levels during LT rejection.

Pre-Existing Intrarenal Parvovirus B19 Infection May Relate to Antibody-Mediated Rejection in Pediatric Kidney Transplant Patients.

Viral infections can lead to transplant dysfunction, and their possible role in rejection is described. In total, 218 protocol biopsies performed in 106 children at 6, 12 and 24 months after transplantation were analyzed according to Banff '15. RT-PCR for cytomegalovirus, Epstein-Barr virus, BK virus and Parvovirus B19 was performed on blood and bioptic samples at the time of transplant and each protocol biopsy. The prevalence of intrarenal viral infection increases between 6 and 12 months after transplantation (24% vs. 44%, p = 0.007). Intrarenal Parvovirus B19 infection is also associated with antibody-mediated rejection (ABMR) (50% ABMR vs. 19% T-cell-mediated rejection, p = 0.04). Moreover, Parvovirus infection is higher at 12 months of follow-up and it decreases at 48 months (40.4% vs. 14%, p = 0.02), while in 24% of grafts, Parvovirus is already detectable at the moment of transplantation. Intrarenal Parvovirus B19 infection seems to be related to ABMR in pediatric kidney recipients. The graft itself may be the way of transmission for Parvovirus, so performance of a PCR test for Parvovirus B19 should be considered to identify high-risk patients. Intrarenal Parvovirus infection presents mainly during the first-year post-transplantation; thus, we recommend an active surveillance of donor-specific antibodies (DSA) in patients with intrarenal Parvovirus B19 infection during this period. Indeed, it should be considered a treatment with intravenous immunoglobulins in patients with intrarenal Parvovirus B19 infection and DSA positivity, even in the absence of ABMR criteria for kidney biopsy.

Micropollutant removal capacity and stability of aquaporin incorporated biomimetic thin-film composite membranes

Aquaporin incorporated nanofiltration membranes have high potential for future applications on separation processes. In this study, performance of biomimetic thin-film composite membranes containing Halomonas elongata and Escherichia coli aquaporins with different affinity tags for the removal of micropollutants was investigated.% rejection of the membranes for atrazine, terbutryn, triclosan, and diuron varied between 66.7% and 90.3% depending on the type of aquaporin and micropollutant. The highest removal rate was achieved with a membrane containing H. elongata aquaporin for atrazine and terbutryn which have methyl branching in their structure. Electrostatic interactions between micropollutants, thin-film layer of the membrane, and tags of aquaporins may also play important role in rejection of micropollutants. Stability experiments showed that biomimetic membranes can be used for six months period without a remarkable decrease in% rejection. Membrane used 24 times for atrazine removal for a year period lost most of its ability to repel atrazine.

Emerging Concepts of Tissue-resident Memory T Cells in Transplantation.

In this review, we summarize and discuss recent advances in understanding the characteristics of tissue-resident memory T cells (TRMs) in the context of solid organ transplantation (SOT). We first introduce the traditionally understood noncirculating features of TRMs and the key phenotypic markers that define this population, then provide a detailed discussion of emerging concepts on the recirculation and plasticity of TRM in mice and humans. We comment on the potential heterogeneity of transient, temporary resident, and permanent resident T cells and potential interchangeable phenotypes between TRM and effector T cells in nonlymphoid tissues. We review the literature on the distribution of TRM in human nonlymphoid organs and association of clinical outcomes in different types of SOT, including intestine, lung, liver, kidney, and heart. We focus on both tissue-specific and organ-shared features of donor- and recipient-derived TRMs after transplantation whenever applicable. Studies with comprehensive sample collection, including longitudinal and cross-sectional controls, and applied advanced techniques such as multicolor flow cytometry to distinguish donor and recipient TRMs, bulk, and single-cell T-cell receptor sequencing to track clonotypes and define transcriptome profiles, and functional readouts to define alloreactivity and proinflammatory/anti-inflammatory activities are emphasized. We also discuss important findings on the tissue-resident features of regulatory αβ T cells and unconventional γδ T cells after transplantation. Understanding of TRM in SOT is a rapidly growing field that urges future studies to address unresolved questions regarding their heterogeneity, plasticity, longevity, alloreactivity, and roles in rejection and tolerance.

Whole-Genome Sequencing Reveals Genetic Variant at the HLA Locus Associated with Graft Failure After Heart Transplantation

<h3>Purpose</h3> Graft failure is the leading cause of death in heart transplant recipients. Rejection related injuries are important contributors, to which genetic factors may contribute. The purpose of this study was to assess genetic variants associated with graft failure after heart transplantation using a genetic association study approach based on whole-genome data, focusing on the major histocompatibility complex gene map on chromosome 6, where the HLA locus is located. <h3>Methods</h3> The study included endomyocardial biopsies from patients who had undergone heart transplantation at Skane University Hospital, Lund, Sweden, between 1988 and 2009. Only recipient samples were included. Patients with at least one grade 2R rejection episode after transplantation were included, as well as a control group with no grade 2R rejection episodes and survival > 10 years. DNA was extracted from endomyocardial biopsies and whole-genome sequencing was conducted. A genetic association analysis was performed. <h3>Results</h3> Genetic association analysis was conducted on a total of 34 patients using 22,347 single nucleotide variants (SNVs). After Bonferroni correction, one SNV, rs66723041, in the gene HLA-DRB6 had a p-value of <2.24× 10-6 (p = 0.05/22347). In total, nine associations yielded p < 1x10-5, including four variants associated with graft failure after heart transplantation, rs66723041 (1.88 x 10-6), rs79617281 (4.23 x 10-6), rs68123256 (6.28 x 10-6) and rs66758173 (6.28 x 10-6) in the gene HLA-DRB6. <h3>Conclusion</h3> This study presents a genomic variant at HLA-DRB6 associated with graft failure after heart transplantation. Along with this finding, a cluster of SNVs with low p-value were also observed at HLA-DRB6, a gene with a documented role in rejection, supporting the validity of the approach to identify relevant biological pathways. Expansion to larger sample sizes and the entire genome may facilitate the development of new pharmaceutical targets and biomarkers.

Monocytes and Macrophages in Kidney Transplantation and Insights from Single Cell RNA-Seq Studies.

Single-cell RNA sequencing (scRNA-seq) is a powerful technology that allows for the identification of minority cell types in complex tissues, such as immune cells in the kidney. Previously, gene expression from infrequent cell types was missed using bulk RNA-sequencing methods due to an averaging effect. Additionally, scRNA-seq facilitates assignment of cell origin in a sample, a shortcoming of previous bulk sequencing technologies. Thus, scRNA-seq is ideal to study the immune cell landscape and the alloimmune response in the human kidney transplant. However, there are few studies published to date. Macrophages are known to play an important role in health and disease in the kidney. Furthermore, it is known that macrophages play key roles in rejection of the kidney transplant. The definition, ontogeny, and function of these cells is complex and nomenclature has evolved as new technologies have become available. In this review, an overview is provided of monocyte and macrophage nomenclature, ontogeny, and function, with a specific focus on kidney transplantation, and including novel scRNA-seq findings. scRNA-seq offers an unbiased transcriptional approach to defining macrophages and provides insights into macrophage ontogeny and function not possible with contemporary methods.

Abstract P393: Fabrication Of Immunomodulatory Hydrogels For Cardiac Repair After Acute Myocardial Infaction

Introduction: The balance of pro- and anti-inflammatory processes is tightly linked to left ventricular remodeling after myocardial infarction. Immune activation also plays a key role in rejection of transplanted allogeneic stem cells. In this study, we present the design, fabrication and characterization of immunomodulatory chitosan-based hydrogels for cardiac repair after myocardial infarction. Methods: Chitosan hydrogels conjugated with small immunomodulatory molecules were synthesized through a thermogelation process. Resultant hydrogels were characterized using scanning electron microscopy and Fourier-transformed infrared spectroscopy. Human mesenchymal stem cells were encapsulated into the hydrogels and biocompatibility was assessed after one week using fluorescence microscopy and a colorimetric assay. Immunomodulatory activity was assessed after co-culture with human T-lymphocytes using flow cytometry for CD4+IFN-γ+ pro-inflammatory and CD4+CD25+FoxP3+ regulatory T-lymphocytes. Results: Small immunomodulatory molecules were successfully integrated into chitosan hydrogels. Physico-chemical characterization revealed no significant changes to the 3D structure and porosity of hydrogels. The addition of 10μM atorvastatin or 10μM rosuvastatin did not result in significant cytotoxicity to encapsulated mesenchymal stem cells at 3 or 7 days. Addition of statins resulted in marked suppression of CD4+ T-lymphocyte proliferation (Control 25.1 Fold, Atorvastatin 1.0 Fold, Rosuvastatin 2.3 Fold, p&lt;0.001) and activation (CD4+IFN-γ+ Population: Control 87.1%, Rosuvastatin 23.7%, p&lt;0.001) after stimulation. No differences were seen in percentages of CD4+CD25+FoxP3+ regulatory T-lymphocytes (Control 5.5%, Rosuvastatin 5.7%, ns). Conclusion: A biocompatible immunomodulatory hydrogel was created through integration of atorvastatin and rosuvastatin into a chitosan hydrogel. Experiments are currently underway in vivo to examine its usefulness for stem cell delivery and reducing adverse left ventricular remodeling after myocardial infarction.

Comparison of De Novo Donor Specific and Non-Specific Antibodies on the Outcome after Heart Transplantation

Purpose Studies have shown that donor specific antibodies (DSA) have great impact on the clinical course and overall survival of patients after heart transplantation (HTx). De-novo non-DSA (NSA) were associated with graft loss after kidney transplantation, but it remains unclear to what extent NSA play a role in rejection, graft function and overall mortality after HTx. The aim of this study was to analyze and compare the outcome of patients with DSA and NSA after HTx. Methods Surveillance endomyocardial biopsies (EMB) were taken after 1, 3, 6 months and yearly for 5 years after HTX, and cardiac allograft vasculopathy (CAV) was evaluated via coronary angiography. Serum HLA-class I and II antibodies were collected for analysis of donor specifity twice yearly. The antibody mean fluorescence intensity (MFI) cut-off values were set at >1000. Study data was collected retrospectively from internal medical records. End points of the study were death of any cause, primary graft failure (PGF), biopsy proven acute cellular rejection (BPACR) ≥2R according to ISHLT, antibody mediated rejection (AMR) and CAV. Complete data was obtained only from patients with a survival of 12 months or greater. Results 69 patients with a follow-up time of min. 18 months to max. 6 years after HTx were divided into two groups (G1: no DSA or NSA present, n=41, G2: DSA and / or NSA present, n=27). G2 was further divided into two subgroups, patients with both DSA + NSA (n=9) and only NSA(n=26) status.All-cause mortality was n=21 (30.9%), with significant difference amongst the groups (G1: n=17 (41.5%), G2: n=4(18.4%)). This trend was also seen amongst cardiovascular mortality (G1: n=7 (17.1%), G2: n=0). No statistically significant difference was seen regarding CAV (G1: n=3 (7.3%), G2: n=2 (7.4%)), BPACR (G1: n=19 (27.9%) or G2: n=9 (22%)). Surprisingly, AMR was seen in patients in G1 n=3 (4.4%), but not in G2 (n=0), however, without statistically relevant difference. Conclusion Our study shows that DSA and NSA had no negative impact on the outcome up to 6 years after HTx. This might be due to a closer monitoring of the patients after detection of DSA and NSA, and, consequently, an adequate and early adjustment of immunosuppressive therapy including specific DSA treatments to preserve graft function.

Removal of Chromium from Water Environment by Forward Osmosis System

Forward osmosis (FO) technology has been applied for removal of chromium (Cr) from water environment. Comparison of the removal efficiency of Cr(VI) and Cr(III) was investigated by changing several operational conditions. The pH of feed solution plays an important role in rejection of Cr. The Cr(VI) rejection was increased with increasing pH, while Cr(III) rejection was stable. It also demonstrated that the rejection of Cr was higher when the membrane active layer faces the feed solution compared to the rejection when the membrane active layer faces the draw solution.

Meltblown fabric vs nanofiber membrane, which is better for fabricating personal protective equipments.

The coronavirus disease 2019 (COVID-19) pandemic has led to a great demand on the personal protection products such as reusable masks. As a key raw material for masks, meltblown fabrics play an important role in rejection of aerosols. However, the electrostatic dominated aerosol rejection mechanism of meltblown fabrics prevents the mask from maintaining the desired protective effect after the static charge degradation. Herein, novel reusable masks with high aerosols rejection efficiency were fabricated by the introduction of spider-web bionic nanofiber membrane (nano cobweb-biomimetic membrane). The reuse stability of meltblown and nanofiber membrane mask was separately evaluated by infiltrating water, 75% alcohol solution, and exposing under ultraviolet (UV) light. After the water immersion test, the filtration efficiency of meltblown mask was decreased to about 79%, while the nanofiber membrane was maintained at 99%. The same phenomenon could be observed after the 75% alcohol treatment, a high filtration efficiency of 99% was maintained in nanofiber membrane, but obvious negative effect was observed in meltblown mask, which decreased to about 50%. In addition, after long-term expose under UV light, no filtration efficiency decrease was observed in nanofiber membrane, which provide a suitable way to disinfect the potential carried virus. This work successfully achieved the daily disinfection and reuse of masks, which effectively alleviate the shortage of masks during this special period.

Removal of arsenic(V) by nanofiltration: Impact of water salinity, pH and organic matter

Climate change will affect water quality through a change in salinity, pH and organic matter (OM) content due to seawater intrusion, temperature change and subsurface biological processes. Therefore, a systematic evaluation of the impact of water quality variations is of particular importance to maintain the performance of a treatment process designed for drinking water. In this work, nanofiltration (NF) was investigated for the treatment of arsenic (As) contaminated water with the emphasis on water chemistry. Water salinity variations had no impact on the high rejection of As(V) with the studied NF membranes (NF270, NF90). The pH affects speciation and this significantly influenced the rejection of As(V) with NF270 (10–86%). The predominant mechanism was charge exclusion, while no effect was observed with NF90 (85–94%) where size exclusion plays the major role in rejection. The presence of humic acid (HA) in water has enhanced the rejection As(V) overall (10–20%) depending on water chemistry (pH, salinity) and membrane type. This study showed that NF technology was effective for As(V) rejection from water where seasonal changes in water quality can occur.

CAN EPITOPE MATCHING OUTMATCH TRADITIONAL HLA MATCHING?

Collaborative Transplant Study. Introduction: Pre-transplant presence and post-transplant development of alloantibodies against highly polymorphic human leukocyte antigen (HLA) allele mismatches (mm) play a major role in rejection of kidney allografts. However, antibodies recognize small sequences on HLA alleles called epitopes and the same epitope can be present on different alleles, impairing the precision of matching. Using the Collaborative Transplant Study database, we analyzed whether a T-cell epitope-based matching of donor-recipient pairs using the PIRCHE-II algorithm is a better predictor of graft survival than the currently applied allele group-based HLA-A, -B, -DR matching. Methods: 68,606 European deceased donor kidney-only transplantations during 1996–2016 were analyzed. PIRCHE-II mismatch score was calculated based on split typing using the 2007 NMDP haplotype frequency database and the PIRCHE matching service. Multivariable Cox regression analyses were performed to calculate hazard ratios (HRs) for death-censored graft loss. Correlation was analyzed with Spearman’s rank correlation. In order to achieve comparable HRs, a log-transformed PIRCHE-II score was used, followed by a linear transformation to match the value range of 0–6 HLA A+B+DR mm. Linear transformations in Cox regression analysis change the HR per point without changing the P- and Z-values. Results and Discussion: The HLA mismatch-derived PIRCHE-II score correlated strongly with the number of HLA mm (correlation coefficient ρ=0.65, P<0.001). Cox regression analyses revealed that Pirche II score and HLA mm are predictive confounders for death-censored graft loss at year 5 with highly significant prognostic power (Z-value for Pirche II: 9.8; for HLA: 11.2; P<0.001) (Table 1).The full Cox model per transformed PIRCHE-II score without HLA mm resulted in a hazard ratio (HR) for graft loss of 1.102 (95% CI=1.081–1.123; P<0.001). When HLA mm were added to the model, the HR per PIRCHE-II score decreased to 1.042 but remained statistically significant (95% CI=1.015–1.071; P=0.002) (Table 1). Overall, considering the HLA loci currently used for typing at split antigen level, HLA mm still had a higher predictive value than the PIRCHE-II score (11.2 vs. 9.8) regarding graft survival. As illustrated in Figure 1, the variance in PIRCHE-II score increased with higher number of HLA mm.Therefore, the possible clinical benefit of PIRCHE-II score matching improved with higher number of HLA mismatches. As demonstrated in Table 1, the risk of graft loss increases with each additional PIRCHE-II score. Conclusion: Our results indicate that PIRCHE-II score is useful and can be included into matching algorithms. However, it cannot fully replace traditional HLA matching. There seems to be information on immunological differences PIRCHE-II score cannot cover in its present form using HLA typing data at split level. This needs to be analyzed also for HLA matching at 4-digit molecular typing level.

Non-HLA Abs in Solid Organ Transplantation

The role of anti-HLA antibodies in solid organ rejection is well established and these antibodies are routinely monitored both in patients in the waiting list and in the post-transplant setting. More recently, the presence of other antibodies directed towards non-HLA antigens, or the so-called minor histocompatibility antigens, has drawn the attention of the transplant community; however, their possible involvement in the graft outcome remains uncertain. These antibodies have been described to possibly have a role in rejection and allograft failure. This review focuses on the most studied non-HLA antibodies and their association with different clinical outcomes considered in solid organ transplantation with the aim of clarifying their clinical implication and potential relevance for routine testing.

Harnessing Expressed Single Nucleotide Variation and Single Cell RNA Sequencing To Define Immune Cell Chimerism in the Rejecting Kidney Transplant.

In solid organ transplantation, donor-derived immune cells are assumed to decline with time after surgery. Whether donor leukocytes persist within kidney transplants or play any role in rejection is unknown, however, in part because of limited techniques for distinguishing recipient from donor cells. Whole-exome sequencing of donor and recipient DNA and single-cell RNA sequencing (scRNA-seq) of five human kidney transplant biopsy cores distinguished immune cell contributions from both participants. DNA-sequence comparisons used single nucleotide variants (SNVs) identified in the exome sequences across all samples. Analysis of expressed SNVs in the scRNA-seq data set distinguished recipient versus donor origin for all 81,139 cells examined. The leukocyte donor/recipient ratio varied with rejection status for macrophages and with time post-transplant for lymphocytes. Recipient macrophages displayed inflammatory activation whereas donor macrophages demonstrated antigen presentation and complement signaling. Recipient-origin T cells expressed cytotoxic and proinflammatory genes consistent with an effector cell phenotype, whereas donor-origin T cells appeared quiescent, expressing oxidative phosphorylation genes. Finally, both donor and recipient T cell clones within the rejecting kidney suggested lymphoid aggregation. The results indicate that donor-origin macrophages and T cells have distinct transcriptional profiles compared with their recipient counterparts, and that donor macrophages can persist for years post-transplantation. Analysis of single nucleotide variants and their expression in single cells provides a powerful novel approach to accurately define leukocyte chimerism in a complex organ such as a transplanted kidney, coupled with the ability to examine transcriptional profiles at single-cell resolution.

Elevated Monocyte Count and Loss of Renal Function in Renal Transplant Patients

BackgroundRejection is an important factor affecting graft function in renal transplant patients. Development of acute rejection even after induction treatment suggests that humoral and cellular immune systems are not the only mechanisms responsible for this event. The innate immune system can play roles in rejection. The aim of this study is to evaluate the association between renal function and some absolute values and ratios of various hematologic parameters assessed before and after renal transplantation. MethodsThis study included 63 renal transplant patients. Demographic features and laboratory findings were reviewed retrospectively and recorded. For cadaveric and spousal transplantations, induction treatment used antithymocyte globulin (ATG) (group 1 [G1]), and CD25 inhibitor was used for the others (group 2 [G2]). G2 was divided into 2 subgroups based on the estimated glomerular filtration rate (eGFR) decline rate: ≤ 3.5 mL/min/y as group 2a (G2a) and > 3.5 mL/min/y as group 2b (G2b). Hematologic parameters were compared across the groups. ResultsCompared to G1, G2 had higher mean blood pressure, blood urea nitrogen, creatinine, and first month post-transplant lymphocyte and monocyte counts (P = .034, P = .040, P = .003, P = .027, and P = .027, respectively). G2a had higher levels of first-month post-transplant white blood cell, monocyte, and neutrophil counts compared to G2b (P = .018, P = .038, and P = .011, respectively). Receiver operating characteristic analysis of the parameters in G2b showed that a monocyte count of > 750 mm3 was associated with the decline in eGFR. ConclusionElevated monocyte count in patients who had faster eGFR decline and did not receive induction treatment with ATG points to the significance of the innate immune system.

Quantum Versus Classical Entanglement: Eliminating the Issue of Quantum Nonlocality

We analyze the interrelation of quantum and classical entanglement. The latter notion is widely used in classical optic simulation of some quantum-like features of light. We criticize the common interpretation that “quantum nonlocality” is the basic factor differing quantum and classical realizations of entanglement. Instead, we point to the breakthrough Grangier et al. experiment on coincidence detection which was done in 1986 and played the crucial role in rejection of (semi-)classical field models in favor of quantum mechanics. Classical entanglement sources produce light beams with the coefficient of second order coherence g^{(2)}(0) ge 1. This feature of classical entanglement is obscured by using intensities of signals in different channels, instead of counting clicks of photo-detectors. The interplay between intensity and clicks counting is not just a technicality. We elevate this issue to the high foundational level.

The TreaT-Assay: A Novel Urine-Derived Donor Kidney Cell-Based Assay for Prediction of Kidney Transplantation Outcome

Donor-reactive immunity plays a major role in rejection after kidney transplantation, but analysis of donor-reactive T-cells is not applied routinely. However, it has been shown that this could help to identify patients at risk of acute rejection. A major obstacle is the limited quantity or quality of the required allogenic stimulator cells, including a limited availability of donor-splenocytes or an insufficient HLA-matching with HLA-bank cells. To overcome these limitations, we developed a novel assay, termed the TreaT (Transplant reactive T-cells)-assay. We cultivated renal tubular epithelial cells from the urine of kidney transplant patients and used them as stimulators for donor-reactive T-cells, which we analyzed by flow cytometry. We could demonstrate that using the TreaT-assay the quantification and characterization of alloreactive T-cells is superior to other stimulators. In a pilot study, the number of pre-transplant alloreactive T-cells negatively correlated with the post-transplant eGFR. Frequencies of pre-transplant CD161+ alloreactive CD4+ T-cells and granzyme B producing alloreactive CD8+ T-cells were substantially higher in patients with early acute rejection compared to patients without complications. In conclusion, we established a novel assay for the assessment of donor-reactive memory T-cells based on kidney cells with the potential to predict early acute rejection and post-transplant eGFR.