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Transplant International : Official... Jan 2020Recognition of non-self structures on donor cells represents the main immunological barrier in solid organ transplantation. The human leukocyte antigens (HLA) are... (Review)
Review
Recognition of non-self structures on donor cells represents the main immunological barrier in solid organ transplantation. The human leukocyte antigens (HLA) are considered the most important non-self (allo)antigens in transplantation. Long-term graft attrition is mainly caused by the formation of alloreactive antibodies that are directed against non-self structures (i.e., epitopes) on cell surface proteins. Recently published data provided evidence for a similar importance of non-HLA mismatches between donors and recipients in acute rejection as well as long-term kidney allograft survival. These data suggest a broader concept of immunological non-self that goes beyond HLA incompatibility and expands the current concept of polymorphic non-self epitopes on cell surface molecules from HLA to non-HLA targets. Amino acid substitutions caused by single nucleotide variants in protein-coding genes or complete loss of gene expression represent the basis for polymorphic residues in both HLA and non-HLA molecules. To better understand these novel insights in non-HLA alloimmunity, we will first review basic principles of the alloimmune response with a focus on the HLA epitope concept in donor-specific antibody formation before discussing key publications on non-HLA antibodies.
Topics: Epitopes; Graft Rejection; Graft Survival; HLA Antigens; Histocompatibility; Humans; Kidney Transplantation; Membrane Proteins
PubMed: 31650645
DOI: 10.1111/tri.13546 -
Frontiers in Immunology 2023Antibody-mediated rejection is the leading cause of kidney graft dysfunction. The process of diagnosing it requires the performance of an invasive biopsy and subsequent... (Review)
Review
Antibody-mediated rejection is the leading cause of kidney graft dysfunction. The process of diagnosing it requires the performance of an invasive biopsy and subsequent histological examination. Early and sensitive biomarkers of graft damage and alloimmunity are needed to identify graft injury and eventually limit the need for a kidney biopsy. Moreover, other scenarios such as delayed graft function or interstitial fibrosis and tubular atrophy face the same problem. In recent years, interest has grown around extracellular vesicles, specifically exosomes actively secreted by immune cells, which are intercellular communicators and have shown biological significance. This review presents their potential as biomarkers in kidney transplantation and alloimmunity.
Topics: Kidney Transplantation; Extracellular Vesicles; Kidney; Exosomes; Biomarkers
PubMed: 37662919
DOI: 10.3389/fimmu.2023.1154650 -
Frontiers in Immunology 2022Allograft rejection remains the major hurdle in lung transplantation despite modern immunosuppressive treatment. As part of the alloreactive process, B cells are... (Review)
Review
Allograft rejection remains the major hurdle in lung transplantation despite modern immunosuppressive treatment. As part of the alloreactive process, B cells are increasingly recognized as modulators of alloimmunity and initiators of a donor-specific humoral response. In chronically rejected lung allografts, B cells contribute to the formation of tertiary lymphoid structures and promote local alloimmune responses. However, B cells are functionally heterogeneous and some B cell subsets may promote alloimmune tolerance. In this review, we describe the current understanding of B-cell-dependent mechanisms in pulmonary allograft rejection and highlight promising future strategies that employ B cell-targeted therapies.
Topics: B-Lymphocytes; Graft Rejection; Humans; Lung; Lung Diseases; Lung Transplantation; Transplantation, Homologous
PubMed: 35320934
DOI: 10.3389/fimmu.2022.845867 -
Current Opinion in Organ Transplantation Feb 2010We provide evidence for the role of de-novo development of immune responses to self-antigens in the posttransplant period and its possible induction by alloimmunity in... (Review)
Review
PURPOSE OF REVIEW
We provide evidence for the role of de-novo development of immune responses to self-antigens in the posttransplant period and its possible induction by alloimmunity in the pathogenesis of chronic rejection following lung, heart and kidney transplantation. The present review details recent findings for the two distinct yet interdependent immune processes in the immunopathogenesis of chronic rejection.
RECENT FINDINGS
The contribution of both humoral and cell-mediated alloimmune responses against mismatched donor histocompatibility antigens (HLA) in the pathogenesis of chronic rejection is well established. Recent studies have focused on development of immune responses to self-antigens during the posttransplant period and its correlation with chronic rejection. These self-antigens include myosin and vimentin in cardiac, K-alpha-1-tubulin and collagen-V in lung and angiotensin II type 1 receptor, collagen-IV and VI in kidney transplants. During the posttransplant period, the development of immune responses to self-antigens is facilitated by induction of a distinct subset of autoreactive T-helper cells referred to as Th17 cells.
SUMMARY
Following organ transplantation, tissue injury and remodeling inflicted by antibodies (Abs) to HLA antigens is conducive to develop autoimmunity. Abs to HLA and self-antigens are detectable in the serum of transplant recipients who develop chronic rejection. Anti-HLA Abs are often present transiently but precede the development of Abs to self-antigens.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmunity; Chronic Disease; Graft Rejection; Graft Survival; HLA Antigens; Humans; Immunity, Cellular; Immunity, Humoral; Isoantibodies; Organ Transplantation; Transplantation Tolerance; Treatment Outcome
PubMed: 19898237
DOI: 10.1097/MOT.0b013e3283342780 -
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 -
American Journal of Transplantation :... Jun 2009Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients.... (Review)
Review
Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients. While alloimmunity has a definite role, there is increasing interest in overall allograft injury and subsequent inflammation and remodeling. This review deals with nonalloimmune factors that may potentiate alloimmune injury. We discuss infection and reflux/aspiration as examples of allograft injury, which may lead to chronic loss of graft function and BOS. Surgical and nonsurgical treatments aimed at preventing these insults and improving survival are considered. The need for further evidence, including randomized-controlled trials, to evaluate the role of medical and surgical therapies is emphasized by the current literature.
Topics: Azithromycin; Bronchiolitis Obliterans; Gastroesophageal Reflux; Gram-Negative Bacterial Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung Diseases; Lung Transplantation; Pneumonia; Pneumonia, Aspiration; Transplantation, Homologous
PubMed: 19459806
DOI: 10.1111/j.1600-6143.2009.02648.x -
Transplant International : Official... Aug 2019Late antibody-mediated rejection (ABMR) is a cardinal cause of kidney allograft failure, manifesting as a continuous and, in contrast with early rejection, often... (Review)
Review
Late antibody-mediated rejection (ABMR) is a cardinal cause of kidney allograft failure, manifesting as a continuous and, in contrast with early rejection, often clinically silent alloimmune process. While significant progress has been made towards an improved understanding of its molecular mechanisms and the definition of diagnostic criteria, there is still no approved effective treatment. In recent small randomized controlled trials, therapeutic strategies with promising results in observational studies, such as proteasome inhibitor bortezomib, anti-C5 antibody eculizumab, or high dose intravenous immunoglobulin plus rituximab, had no significant impact in late and/or chronic ABMR. Such disappointing results reinforce a need of new innovative treatment strategies. Potential candidates may be the interference with interleukin-6 to modulate B cell alloimmunity, or innovative compounds that specifically target antibody-producing plasma cells, such as antibodies against CD38. Given the phenotypic heterogeneity of ABMR, the design of adequate systematic trials to assess the safety and efficiency of such therapies, however, is challenging. Several trials are currently being conducted, and new developments will hopefully provide us with effective ways to counteract the deleterious impact of antibody-mediated graft injury. Meanwhile, the weight of evidence would suggest that, when approaching using existing treatments for established antibody-mediated rejection, "less may be more".
Topics: Allografts; Animals; Antibodies, Monoclonal, Humanized; Bortezomib; Graft Rejection; Graft Survival; Histocompatibility; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Isoantibodies; Kidney Transplantation; Proteasome Inhibitors; Randomized Controlled Trials as Topic; Rituximab; Transplantation, Homologous
PubMed: 30955215
DOI: 10.1111/tri.13436 -
Asian Journal of Transfusion Science 2020Alloimmunization is an immune response against foreign antigens which introduced into the body through transfusion, pregnancy, or transplantation. This phenomenon is a... (Review)
Review
BACKGROUND
Alloimmunization is an immune response against foreign antigens which introduced into the body through transfusion, pregnancy, or transplantation. This phenomenon is a big challenge in patients, which require regular transfusions. In the current study, we tried to have a comprehensive review on the status of alloimmunization in Iran. For this purpose, we searched for papers investigating alloimmunization in transfusion-dependent patients and also in patients with no regular transfusions who are candidate for surgery or who need blood.
METHODS
We searched PubMed, Google Scholar, SID, and MAGIRAN databases using the following keywords: "blood transfusion," "alloimmunization," "alloantibodies," "irregular antibodies," "red cell antibodies," and "Iran." No limitation for the date of publication and language of the papers was defined. All the identified records were then screened for the relevance and duplication.
RESULTS
A total of 22 papers were included in this study. All of the studies were conducted from 1999 to 2016 and providing alloimmunization data from different cities all over of Iran. In general, the results showed that the most prevalent alloantibodies are anti-Kell (anti-K antigen) and anti-Rh system, mainly anti-E, anti-D, anti-C, and anti-c.
CONCLUSION
Anti-Kell and anti-Rh antibodies are the most prevalent antibodies responsible for alloimmunization in Iranian population.
PubMed: 33162697
DOI: 10.4103/ajts.AJTS_137_17 -
The Cochrane Database of Systematic... 2000The development of Rh immunisation and its prophylactic use since the 1970s has meant that severe Rhesus D (RhD) alloimmunisation is now rarely seen. (Review)
Review
BACKGROUND
The development of Rh immunisation and its prophylactic use since the 1970s has meant that severe Rhesus D (RhD) alloimmunisation is now rarely seen.
OBJECTIVES
The objective of this systematic review was to assess the effects of giving anti-D to Rhesus negative women, with no anti-D antibodies, who had given birth to a Rhesus positive infant.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register, MEDLINE (from 1966 to January 1999) and reference lists of relevant articles. Date of last search of Cochrane Controlled Trials Register: January 1999.
SELECTION CRITERIA
Randomised trials in Rhesus negative women without antibodies who were given anti-D immunoglobulin postpartum compared with no treatment or placebo.
DATA COLLECTION AND ANALYSIS
Assessments of inclusion criteria, trial quality and data extraction were done by each author independently. Initial analyses included all trials. Other analyses assessed the effect of trial quality, ABO compatibility and dose.
MAIN RESULTS
Six eligible trials compared postpartum anti-D prophylaxis with no treatment or placebo. The trials involved over 10,000 women, but trial quality varied. Anti-D lowered the incidence of RhD alloimmunisation six months after birth (relative risk 0.04, 95% confidence interval 0.02 to 0.06), and in a subsequent pregnancy (relative risk 0.12, 95% confidence interval 0. 07 to 0.23). These benefits were seen regardless of the ABO status of the mother and baby and when anti-D was given within 72 hours of birth. Higher doses (up to 200 micro grams) were more effective than lower doses (up to 50 micro grams) in preventing RhD alloimmunisation in a subsequent pregnancy.
REVIEWER'S CONCLUSIONS
Anti-D, given within 72 hours after childbirth, reduces the risk of RhD alloimmunisation in Rhesus negative women who have given birth to a Rhesus positive infant. However the evidence on the optimal dose is limited.
Topics: Female; Humans; Postpartum Period; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 10796089
DOI: 10.1002/14651858.CD000021 -
Current Opinion in Organ Transplantation Dec 2021Obesity is a worldwide health problem with increasing rates in both children and adults. Bariatric surgery (BS) represents the only effective long-term treatment.... (Review)
Review
PURPOSE OF REVIEW
Obesity is a worldwide health problem with increasing rates in both children and adults. Bariatric surgery (BS) represents the only effective long-term treatment. Beneficial effects of BS may be mediated through shifts of the gut microbiome. Here, we introduce data linking the microbiome to alloimmune responses.
RECENT FINDINGS
The rapid development of microbiome sequencing technologies in addition to the availability of gnotobiotic facilities have enabled mechanistic investigations on modulations of alloimmune responses through microbiomes. BS has been shown to improve comorbidities and chronic inflammation caused by obesity. Changes in microbiota and microbiota-related metabolites may play a role. Patients either listed or having received a transplant have undergone weight loss surgery, thus allowing to dissect mechanisms of microbial shifts to alloimmunity.
SUMMARY
Weight loss and BS have the potential to improve transplant outcomes by ameliorating alloimmune responses. Those effects may be carried out through alterations of the gut microbiome.
Topics: Adult; Bariatric Surgery; Child; Gastrointestinal Microbiome; Humans; Microbiota; Obesity; Weight Loss
PubMed: 34714789
DOI: 10.1097/MOT.0000000000000920