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Human leukocyte antigen alloimmunization is caused by exposure to HLA antigens through transfusion, pregnancy, or transplant. Our study objective was to present the rate of positivity of anti-HLA antibody considering the effects of a single sensitization event in kidney transplant candidates at our center.Our study reviewed 606 kidney transplant candidates. Patient sera were analyzed using Luminex xMAP technology. Panel reactive antibody positivity rates and antibody strengths in patients were analyzed according to a single sensitization event.Our findings showed 246 patients (40.6%) with a panel reactive antibody0, of which 97 (39.4%) were sensitized from a single event, 119 (48.4%) were sensitized by multiple events, and 30 (12.2%) had no known sensitizing event. Considering patients sensitized by a single event with a panel reactive antibody0, we found that 25.8% had received transplant only, 49.5% had previous pregnancy only, and 24.7% had received transfusion only. The strength of antibodies was significantly higher in patients with previous transplant procedures than in those with transfusion for HLA-A (P.01), HLA-B (P.05), HLA-C (P.05), HLA-DR (P.001), HLA-DQ (P.05), and HLA-DP (P.05). Similarly, we observed significantly higher median fluorescence intensity values for HLA-A, -DR, -DQ, and -DP loci in patients with a previous transplant procedure versus pregnancy. The strength of antibodies against HLA-DR was significantly higher in patients with a previous pregnancy compared with those with transfusion (P.01).This study documents the profile of HLA alloimmunization in kidney transplant candidates. In particular, transplant procedures appear to have a greater immunologic impact, followed by pregnancy and transfusion. Our data confirm and are in accordance with those of several studies in which the sensitization events were associated with higher prevalence of anti-HLA antibodies.

The identification of human leukocyte antigen (HLA) antibodies in the sera of candidates awaiting organ transplantation has evolved over time. This has been possible because of the introduction of more sensitive techniques and to the increasing focus on the structural aspects of the HLA epitopes. The use of the HLAMatchmaker algorithm in the analysis of positive sera and the verification of HLA ABC epitopes in the HLA Epitope Registry website provide new stimuli on the interpretation of antibody reactivity. The epitopes defined by eplet pairs often involve a nonself-eplet and a self-eplet (nonself-self paradigm), suggesting that the antibody response to an HLA mismatch must have an auto-reactive component. Here, we report an application of the nonself-self paradigm that provides a basis for better knowledge and interpretation of HLA-antibody reactivity in Luminex assays with single alleles.

Over the years, the increasing acquisition of antibiotic resistance genes has led to the emergence of highly resistant bacterial strains and the loss of standard antibiotics’ efficacy, including β-lactam/β-lactamase inhibitor combinations and the last line carbapenems. Klebsiella pneumoniae is considered one of the major exponents of a group of multidrug-resistant ESKAPE pathogens responsible for serious healthcare-associated infections. In this study, we proved the antimicrobial activity of two analogues of Temporin L against twenty carbapenemase-producing K. pneumoniae clinical isolates. According to the antibiotic susceptibility assay, all the K. pneumoniae strains were resistant to at least one other class of antibiotics, in addition to beta-lactams. Peptides 1B and C showed activity on all test strains, but the lipidated analogue C expressed the greater antimicrobial properties, with MIC values ranging from 6.25 to 25 µM. Furthermore, the peptide C showed bactericidal activity at MIC values. The results clearly highlight the great potential of antimicrobial peptides both as a new treatment option for difficult-to-treat infections and as a new strategy of drug-resistance control.

Green and alternative strategies for the preparation of silver nanoparticles (AgNP) are the focus of considerable attention, given their wide range of applications. A clean, eco-friendly, low-cost, scalable and straightforward protocol for the production of AgNP is reported, using hydrolyzed spent coffee grounds (HSCG) both as a reducing agent and a stabilizing matrix. The sample was easily recovered in 50–60% yield by centrifugation and lyophilization. Size and morphological analyses combined with X-ray diffraction analysis indicated ca. 6% w/w incorporation of AgNP of about 20 nm size into the HSCG matrix. AgNP-HSCG exhibited efficient antioxidant properties in several chemical assays and antimicrobial activities (MIC< 0.1 mg/mL) against Gram-negative bacteria such as E. coli and P. aeruginosa. Antibacterial devices made of chitosan films containing AgNP-HSCG were also prepared that showed significant inhibition zones against the same bacterial strains, even at the lowest loading (0.3% w/w) of AgNP, and remarkable antioxidant properties in aqueous media. An economic evaluation of the whole process was carried out, demonstrating that manufacturing of both HSCG and chitosan-based antibacterial devices is a convenient and easy-to-perform process, with the potential of full industrial scalability. Overall, the adopted circular approach, designed to reuse a cheap and abundant agri-food waste while avoiding the use of toxic or noxious chemicals, makes HSCG a practical and easily accessible multifunctional material for the clean and sustainable synthesis of AgNP with adequate size and stability for incorporation in efficient antioxidants and antimicrobial devices.

Purpose Human leukocyte antigen (HLA)-G is a non-classic major histocompatibility complex HLA class I molecule. HLA-G may have tolerogenic properties which are linked to epigenetic-sensitive pathways. There is a correlation of sHLA-G levels and graft acceptance in transplantation studies. There are previous data on correlation of sHLA-G with graft rejection as well as with viral infections such as hepatitis C virus (HCV) in kidney transplanted patients. Here, we report the sHLA-G expression in patients on the waiting list for kidney transplantation, with and without anti-HCV compared to a control group. Methods Serum of 67 patients on the waiting list for kidney transplantation (n = 43 with anti-HCV and n = 24 without anti-HCV) was analyzed. Among these patients, n = 39 were on the waiting list for the first transplantation, while n = 28 were patients who returned in the list. The control group included n = 23 blood donors with anti-HCV (n = 13) and without anti-HCV (n = 10). Results The expression of sHLA-G was significantly lower in the control group (39.6 ± 34.1 U/ml) compared to both - patients on the waiting list for the first transplantation (62.5 ± 42.4 U/ml, p=0.031) and patients who returned in the list (76.7 ± 53.9 U/ml, p=0.006). No significant differences were observed in all anti-HCV positive groups. A positive linear correlation between sHLA-G and TNF-α, and patient age was observed. Conclusions Serum sHLA-G values were significantly increased in both - patients on the waiting list for the first transplantation and patients who returned in the list, as compared to control group. Our findings confirm the key tolerogenic role of sHLA-G levels as epigenetic-related marker for measuring the state of kidney allograft acceptance.

Background Patients with end-stage liver disease (ESLD) have a compromised nutritional status because of the liver crucial role in regulating metabolic homeostasis and energy balance. Data sources A systematic review of literature based on extensive relevant articles published from 2001 to 2017 in English in PubMed database was performed by searching keywords such as liver disease, non-alcoholic liver disease, alcoholic liver disease, malnutrition, epigenetics, gut microbiota, and probiotics. Results Liver transplantation would be one eligible therapy for ESLD patients, even if, the clinical outcome is negatively influenced by malnutrition and/or infections. The malnutrition is a condition of nutrient imbalance with a high incidence in ESLD patients. An accurate evaluation of nutritional status could be fundamental for reducing complications and prolonging the survival of ESLD patients including those undergoing liver transplantation. In addition, the interaction among nutrients, diet and genes via epigenetics has emerged as a potential target to reduce the morbidity and mortality in ESLD patients. The malnutrition induces changes in gut microbiota causing dysbiosis with a probable translocation of bacteria and/or pathogen-derived factors from the intestine to the liver. Gut microbiota contribute to the progression of chronic liver diseases as well as hepatocellular carcinoma. The administration of probiotics modulating gut microbiota could improve all chronic liver diseases. Conclusions This review provides an update on malnutrition status linked to epigenetics and the potential benefit of some probiotics on the management of ESLD patients. In support of this view and to reveal the constant and growing interest in this field, some clinical trials are reported.

To the Editor: We read the article by Dogan and colleagues1 regarding the cardiac effects of chronic graft-versus-host disease (cGVHD) in patients who had undergone allogeneic stem cell transplantation. Chronic GVHD is a severe complication after allogeneic bone marrow transplantation, which is an immunotherapeutic option in several hematologic diseases. Although the pathogenesis of cGVHD remains unclear, it is solidly linked to graft-versus-leukemia (GVL) reactions; the balance between GVHD and the beneficial GVL-effect anticancer capacity of donor immune cells is crucial to the outcome of transplantation. Several variables have been observed clinically, such as the type of disease, the conditioning regimen, and relevant polymorphisms of the genes that might contribute to interpatient variability in alloimmune responses. Investigators in Spain have found that the cytotoxic T-lymphocyte antigen 4 (CTLA-4) CT60 AA genotype is associated with an increased risk of relapse and a higher transplant-related mortality rate.2 In addition, investigators have proposed that the major histocompatibility complex class I chain-related protein A (MICA) is a genetic marker of cGVHD: MICA is a molecule of particular interest because of its participation in non-T-cell receptor-mediated immune function. In particular, Boukouaci and colleagues3 have found that the presence of MICA-129 values increases the risk of cGVHD in an allele dose-dependent manner. Unfortunately, it is unclear how to use these genetic markers as candidate biomarkers for cGVHD in the clinical setting. We agree that high-sensitivity C-reactive protein (hs-CRP) is a useful biomarker in patients in whom cGVHD develops after bone marrow transplantation.4 Other investigators have studied the tissue damage caused by the conditioning regimen, infections, and allogeneic immune reactions accompanying the initial elevation of hs-CRP levels during the course of allogeneic hematopoietic stem cell transplantation.5 These findings indicate the possible association of hs-CRP values with the substantial increase in tissue damage that leads to GVHD.5 However, results of a recent study6 show that cGVHD has no impact on cardiovascular risk and that hs-CRP (which is usually considered to be an important biomarker that predicts the risk of cardiovascular events) does not correlate with profiles of high cardiovascular risk. Hence, does hs-CRP exert a direct cardiac effect through an increase in left ventricular mass, or is it a surrogate biomarker only for cGVHD patients? Future efforts in biomarker discovery and consequent validation are needed for an understanding of the pathogenesis of cGVHD.

Human beta-defensin 2 is an antimicrobial peptide that is produced by several epithelial cells after stimulation with micro-organisms and inflammatory mediators. Gram-negative bacteria, which are typically detected in periodontal pockets in periodontitis, elicit a stronger antibacterial peptide response of human beta-defensin 2 by epithelial cells. In this study, we investigated whether Chlamydia pneumoniae is able both to enter and grow in human gingival fibroblasts (HGF), to modify the production of cytokines, and is involved in regulation of beta-defensin 2 expression. Gingival fibroblasts discarded from periodontal procedures on healthy young individuals were infected with viable C. pneumoniae or with heat- or ultraviolet-inactivated organisms at a multiplicity of infection of 4 inclusion-forming units per cell. Our results demonstrate that after 48 h of incubation with viable C. pneumoniae, gingival fibroblasts showed a proliferative response as seen by both colorimetric assay and direct cell count (40% and 45%, respectively). Moreover, cells incubated with viable or ultraviolet light-inactivated C. pneumoniae organisms showed an increase in the levels of interleukin-6, interleukin-10 and human beta-defensin 2 in a time-dependent fashion, while the cells infected with heat-killed bacteria did not show a significant production either of the cytokines or beta-defensin 2 at any time. In conclusion, we demonstrate the correlation between multiplication of C. pneumoniae in human gingival fibroblasts and release of interleukin-6, interleukin-10 and up-regulation of beta-defensin 2, suggesting that gingival fibroblasts may be a periodontium niche for obligate intracellular C. pneumoniae and may play a role in innate gingival immune system and inflammatory response mechanisms of periodontitis.