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Transplantation Dec 2021Immunological mechanisms linking undernutrition to infection and the alloimmune response are poorly understood in transplantation. We aimed to determine how...
BACKGROUND
Immunological mechanisms linking undernutrition to infection and the alloimmune response are poorly understood in transplantation. We aimed to determine how undernutrition and hypoleptinemia impact T-cell allospecific and cytomegalovirus (CMV) viral-specific immunity in a murine model.
METHODS
Fed, fasted for 48 h (model of undernutrition), and fasted with leptin injections (leptin rescue), C57BL/6 mice received skin grafts from either C57BL/6 (syngeneic) or BALB/c (allogeneic) mice donors. Allograft rejection and survival were monitored. Fed, fasted, and leptin rescue C57BL/6 mice were inoculated with murine cytomegalovirus (mCMV). Mouse spleens were retrieved for T-cell flow cytometry analysis, mCMV DNA extraction, and quantitative polymerase chain reaction. Serum leptin levels were measured with ELISA.
RESULTS
Fasted mice had prolonged rejection-free and graft survival compared with fed mice (P = 0.0002 and P = 0.043). Leptin administration did not alter rejection-free survival or allograft failure. CD8+ central memory T cell and CD8+ effector T cell proportions were significantly lower in fasted mice receiving allogeneic skin transplants compared with fed mice (P = 0.0009 and P = 0.0015). Fasted mice had higher viral loads (P = 0.0028) and impaired mCMV-specific interferon-gamma-producing CD8+ T cells (P = 0.0007), which improved with leptin rescue (P = 0.032).
CONCLUSIONS
Undernutrition and its associated hypoleptinemia correlated with impaired allospecific and viral-specific immunities. Leptin administration decreased mCMV viral burden and increased mCMV-specific T-cell immunity, however, it did not increase rejection or worsen graft survival in complete major histocompatibility complex-mismatched skin allografts. Leptin may be a potential adjunctive therapy for CMV viremia in undernourished transplant recipients.
Topics: Animals; CD8-Positive T-Lymphocytes; Cytomegalovirus; Cytomegalovirus Infections; Graft Rejection; Malnutrition; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL
PubMed: 33724247
DOI: 10.1097/TP.0000000000003743 -
Characterization of pediatric transfusion-dependent thalassemia patients in a large academic center.Journal of Clinical Laboratory Analysis Sep 2023Transfusion-dependent thalassemia patients are at high risk of transfusion-related complications. Yet, there is scanty data on the frequency of transfusion reactions,...
BACKGROUND
Transfusion-dependent thalassemia patients are at high risk of transfusion-related complications. Yet, there is scanty data on the frequency of transfusion reactions, particularity alloimmunization among pediatric transfusion-dependent thalassemia patients. In addition, there is no consensus on the prophylactic antigen matching for prevention of alloimmunization or the extent of antigen matching for alloimmunized thalassemia patients.
METHODS
We conducted a retrospective study to assess the frequency and specificity of alloimmunization among pediatric transfusion-dependent thalassemia patients receiving ABO, RhD, and K-matched red blood cell units. In addition, we studied the association between patients' characteristics and alloimmunization. The clinical and transfusion records of transfusion-dependent thalassemia patients followed up at our institution between July 2018 and June 2022 were reviewed.
RESULTS
Ninety-two transfusion-dependent thalassemia patients having mean age of 13.37 years (SD, 5.56) were included in our study. Eight patients (9%) had developed clinically significant alloantibodies; six patients (6%) developed alloantibody against E antigen while two patients (2%) developed more than one alloantibody. Of alloimmunized patients, five patients had received transfusion outside Canada. Patients' sex, age, having a genotype variant, total number, and duration of transfusion received were not associated with the risk of alloimmunization. The transfusion-recipient's diagnosis of β-thalassemia, having developed autoantibody, and history of receiving transfusion outside Canada were associated with alloimmunization.
CONCLUSION
Blood matching for ABO, RhD, and K antigens resulted in, although not eliminated, lower frequency of alloimmunization than that previously reported among pediatric thalassemia patients. Extending matching to include Rh antigens could further reduce the rate of alloimmunization.
Topics: Humans; Child; Adolescent; Retrospective Studies; Thalassemia; Erythrocytes; beta-Thalassemia; Blood Transfusion; Transfusion Reaction; Blood Group Antigens; Isoantibodies; Anemia, Hemolytic, Autoimmune
PubMed: 37665129
DOI: 10.1002/jcla.24962 -
Blood Reviews Jul 2021Red blood cell (RBC) alloimmunization is a serious complication of blood transfusions, challenging selection of compatible units for future transfusions. Genetic... (Meta-Analysis)
Meta-Analysis Review
Red blood cell (RBC) alloimmunization is a serious complication of blood transfusions, challenging selection of compatible units for future transfusions. Genetic characteristics may be associated with the risk of RBC alloimmunization and may therefore serve to identify high-risk patients. The aim of this systematic review was to summarize the available evidence on genetic risk factors for RBC alloimmunization. Electronic databases were searched up to April 2020 for studies (Search terms included transfusion, alloimmunization and genetic). A total of 2581 alloimmunized cases and 26,558 controls were derived from 24 studies. The alleles that were most frequently studied and that demonstrated significant associations in a meta-analysis with alloimmunization to the Duffy antigen were HLA-DRB1*04 (Odds Ratio 7.80 (95%CI 4.57-13.33)), HLA-DRB1*15 (OR 3.76 (95%CI 2.14-6.59)), and HLA-DRB1*03 (OR 0.12 (95%CI 0.05-0.29)). Furthermore, significant associations with anti-K formation was found for the alleles HLA-DRB1*10 (OR 2.64 (95%CI 1.41-4.95)), HLA*DRB1*11 (OR 2.11, (95%CI 1.34-3.32)), and HLA-DRB1*13 (OR 1.71 (95%CI 1.26-2.33)). Overall, the available evidence was of moderate to low quality, hampering interpretation of reported results. There is an urgent need for high quality evidence on genetic risk factors for RBC alloimmunization.
Topics: Alleles; Blood Group Antigens; Blood Transfusion; Erythrocytes; Genetic Predisposition to Disease; Humans; Immunization; Isoantibodies; Risk Assessment; Risk Factors
PubMed: 33451870
DOI: 10.1016/j.blre.2020.100794 -
The Journal of Heart and Lung... Aug 2021The microbiome is an environmental factor in intricate symbiotic relationship with its hosts' immune system, potentially shaping anticancer immunity, autoimmunity, and... (Review)
Review
The microbiome is an environmental factor in intricate symbiotic relationship with its hosts' immune system, potentially shaping anticancer immunity, autoimmunity, and transplant responses. The focus of this review is to discuss recent findings tying the microbiota to transplant outcomes and alloimmunity. The microbiota changes dynamically following transplantation, but whether these changes affect transplant outcomes can be difficult to parse out. New data reveal effects of the microbiota locally, as well as systemically, depending on the mucosal/epithelial surface colonized, the specific commensal communities present and the nature of microbial-derived molecules produced. These complex interactions result in the microbiota potentially impacting transplantation at different levels, including modulation of donor and/or recipient cells, alterations in the priming and/or effector phases of the alloimmune response, availability or metabolism of immunosuppressive drugs, transplant fate or post-transplant complications.
Topics: Adaptive Immunity; Graft Rejection; Humans; Microbiota; Organ Transplantation; Transplantation Tolerance
PubMed: 34030971
DOI: 10.1016/j.healun.2021.04.004 -
American Journal of Transplantation :... Jul 2011There has been increasing interest in the role played by B cells, plasma cells and their associated antibody in the immune response to an allograft, driven by the need... (Review)
Review
There has been increasing interest in the role played by B cells, plasma cells and their associated antibody in the immune response to an allograft, driven by the need to undertake antibody-incompatible transplantation and evidence suggesting that B cells play a role in acute cellular rejection and in acute and chronic antibody-mediated rejection. A number of immunosuppressive agents have emerged which target B cells, plasma cells and/or antibody, for example, the B cell-depleting CD20 antibody rituximab. This review describes recent developments in the use of such agents, our understanding of the role of B cells in alloimmunity and the application of this knowledge toward novel therapies in transplantation. It also considers the evidence to date suggesting that B cells may act as regulators of an alloimmune response. Thus, future attempts to target B cells will need to address the problem of how to inhibit effector B cells, while enhancing those with regulatory capacity.
Topics: Antibodies, Monoclonal, Murine-Derived; Antigen-Presenting Cells; Antilymphocyte Serum; B-Lymphocytes; Graft Rejection; Humans; Lymphocyte Depletion; Rituximab; Transplantation Immunology
PubMed: 21668625
DOI: 10.1111/j.1600-6143.2011.03554.x -
Polish Archives of Internal Medicine Mar 2017Alloimmunization to human platelet antigens (HPAs) may occur either during pregnancy, when a HPA‑negative mother gives birth to a newborn who inherits HPAs from the... (Review)
Review
Alloimmunization to human platelet antigens (HPAs) may occur either during pregnancy, when a HPA‑negative mother gives birth to a newborn who inherits HPAs from the father, or following blood transfusion or stem cell transplantation. Antiplatelet alloantibodies do not cause thrombocytopenia in a patient, but their detection must always be recorded in medical records because they may induce fetal and neonatal alloimmune thrombocytopenia in present and all subsequent pregnancies, platelet refractoriness, posttransfusion purpura, or prolonged thrombocytopenia with engraftment failure after stem cell transplantation. Passive transfer of platelet alloantibodies through transfused blood components may trigger thrombocytopenia and severe posttransfusion reactions in the recipient. In a Caucasian population, such clinical outcome of platelet alloimmunization is mostly due to anti‑HPA‑1a antibodies, less frequently to anti‑HPA‑5b, anti‑HPA‑1b, and others. Information on anti‑HPA alloantibodies is crucial for the prevention and treatment of their consequences.
Topics: Antigens, Human Platelet; Blood Transfusion; Female; Humans; Isoantibodies; Pregnancy; Stem Cell Transplantation; Transfusion Reaction
PubMed: 28377559
DOI: 10.20452/pamw.3932 -
Transfusion Medicine and Hemotherapy :... Nov 2014In the context of transfusion medicine, alloimmunization most often refers to the development of antibodies to non-ABO red blood cell (RBC) antigens following pregnancy,... (Review)
Review
In the context of transfusion medicine, alloimmunization most often refers to the development of antibodies to non-ABO red blood cell (RBC) antigens following pregnancy, transfusion, or transplantation. The development of RBC alloantibodies can have important clinical consequences, particularly in patients who require chronic transfusions. It has been suggested that alloimmunization is more common in some clinical circumstances and patient populations than in others. As such, individuals that develop alloantibodies are frequently referred to as 'responders' in the medical literature. In contrast, individuals that do not develop alloantibodies despite repeated exposures to non-self blood group antigens have been referred to as 'non-responders'. The purpose of this article is to review the phenomenon of RBC alloimmunization in the context of responders and non-responders to: i) establish a basic framework for alloimmunization as reported across several diverse patient populations; ii) more fully explore literature reports which support the concept of responders/non-responders regarding blood group antigen alloimmunization; iii) summarize the mechanisms that have been shown to predispose an individual to alloimmunization to determine how these factors may differentiate 'responders' from 'non-responders'; and iv) briefly discuss some practical approaches to prevent alloimmunization in patients who may be prone to alloantibody development.
PubMed: 25670929
DOI: 10.1159/000369109 -
Transplant International : Official... Mar 2018This review focuses on the emerging concept of genomewide genetic variation as basis of an alloimmune response. Chronic antibody-mediated rejection is the major cause of... (Review)
Review
This review focuses on the emerging concept of genomewide genetic variation as basis of an alloimmune response. Chronic antibody-mediated rejection is the major cause of long-term graft loss and growing evidence supports the clinical relevance of HLA but also non-HLA related alloimmune responses. Several polymorphic gene products have been identified as minor histocompatibility antigens. The formation of donor-specific alloantibodies is driven by indirect allorecognition of donor-derived peptides representing a form of conventional T-cell response. With the availability of high-throughput sequencing and genotyping technologies, the identification of genomewide genetic variation and thus mismatches between organ donors and graft recipients has become feasible. First clinical data linking genetic polymorphism and clinical outcome have been published and larger studies are currently under way. Protein arrays have successfully been used to identify a large variety of non-HLA antibodies in kidney transplant recipients and the availability of customizable peptide arrays made screening for linear epitopes on an individual patient level feasible. This review provides a summary of the recent findings in histocompatibility matching in the field of solid organ transplantation and complements it with a clear workflow for assessing the impact of genetic differences in protein-coding genes in solid organ transplantation.
Topics: Autoimmunity; Genetic Variation; Genome, Human; Graft Rejection; HLA Antigens; Humans; Isoantibodies; Minor Histocompatibility Antigens; Transplantation Immunology
PubMed: 28865128
DOI: 10.1111/tri.13059 -
American Journal of Transplantation :... Oct 2020The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and... (Review)
Review
The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and utility of alloimmune assays that are currently in use or in development for risk assessment in the setting of organ transplantation. The goal was to determine the precision and clinical feasibility/utility of such assays in evaluating both memory and primary alloimmune risks. The process included a critical review of biologically driven, state-of-the-art, clinical diagnostics literature by experts in the field and an open public forum in a face-to-face meeting to promote broader engagement of the American Society of Transplantation and American Society of Histocompatibility and Immunogenetics membership. This report summarizes the literature review and the workshop discussions. Specifically, it highlights (1) available assays to evaluate the attributes of HLA antibodies and their utility both as clinical diagnostics and as research tools to evaluate the effector mechanisms driving rejection; (2) potential assays to assess the presence of alloimmune T and B cell memory; and (3) progress in the development of HLA molecular mismatch computational scores as a potential prognostic biomarker for primary alloimmunity and its application in research trial design.
Topics: Graft Rejection; Group Processes; HLA Antigens; Histocompatibility; Isoantibodies; Kidney Transplantation
PubMed: 32342639
DOI: 10.1111/ajt.15937 -
Frontiers in Immunology 2024
Topics: Histocompatibility; Transplantation Immunology
PubMed: 38558808
DOI: 10.3389/fimmu.2024.1393026