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Frontiers in Immunology 2022Myeloid-derived suppressor cells (MDSC) are defined as a group of myeloid cells with potent immunoregulatory functions that have been shown to be involved in a variety... (Review)
Review
Myeloid-derived suppressor cells (MDSC) are defined as a group of myeloid cells with potent immunoregulatory functions that have been shown to be involved in a variety of immune-related diseases including infections, autoimmune disorders, and cancer. In organ transplantation, MDSC promote tolerance by modifying adaptive immune responses. With aging, however, substantial changes occur that affect immune functions and impact alloimmunity. Since the vast majority of transplant patients are elderly, age-specific modifications of MDSC are of relevance. Furthermore, understanding age-associated changes in MDSC may lead to improved therapeutic strategies. Here, we provide a comprehensive update on the effects of aging on MDSC and discuss potential consequences on alloimmunity.
Topics: Aged; Aging; Humans; Immune Tolerance; Myeloid Cells; Myeloid-Derived Suppressor Cells; Organ Transplantation
PubMed: 35874716
DOI: 10.3389/fimmu.2022.917972 -
Auto- Immunity Highlights May 2011Fetomaternal alloimmune disease has traditionally been associated with haematological disease such as fetomaternal alloimmune thrombocytopaenia and Rh haemolytic... (Review)
Review
Fetomaternal alloimmune disease has traditionally been associated with haematological disease such as fetomaternal alloimmune thrombocytopaenia and Rh haemolytic anaemia, but is now known to also be organ specific. Alloimmune membranous glomerulonephritis (AMG) is one of the most well understood organ-specific alloimmune diseases. Neonatal haemochromatosis (NH) is a rare condition characterised by early liver failure in infants, with evidence suggesting that it is also alloimmune. Both AMG and NH appear to involve the passive transfer of alloantibodies to the fetus, which bind a specific alloantigen, fix complement and activate the terminal complement cascade. Although differences between AMG and NH are known, and evidence of the presence of antigen-specific alloantibodies in NH is still missing, we will use AMG as an example of fetomaternal organ specific alloimmune disease, and critically compare this to other emerging evidence that indicates that NH is also alloimmune.
PubMed: 26000116
DOI: 10.1007/s13317-011-0019-7 -
Revue Medicale de Liege Jun 2002Allogenic blood transfusion may be required for the treatment of anemia due to a hematologic disease, the consequences of chemotherapy or other circumstances, such as... (Review)
Review
Allogenic blood transfusion may be required for the treatment of anemia due to a hematologic disease, the consequences of chemotherapy or other circumstances, such as haemorrage and/or surgery. Transfusion becomes indispensable to prevent the side effects of anemia, such as hypoxia, palpitations, tachycardia, cardiac ischemia and fatigue. However, frequent transfusions can cause several acute problems such as hemolysis, anaphylactic shock and septic shock but also chronic problems such as iron overload (hemochromatosis), alloimmunisation and metabolic disturbances. Each of these complications can produce serious consequences and could even be sometimes fatal. Therefore we should recognise, prevent and if necessary treat all these hazards. Our article emphasises the potential chronic problems. For hemochromatosis, an iron chelator (deferoxamine) should be administered. In the presence of allo-immunisation the more compatible ABO blood group must be chosen and blood products be eliminated by filtration, when there has been blood reaction. When an allo-graft of hematopoitic tissues is considered an irradiation of blood products is necessary. Research is being carried out to develop substitute products for transfusion (haemoglobine solutions) or molecules acting on the syntheses of haemoglobine (butyrate arginine). The efficacy of erythropoitine, (EPO) is well recognised for stimulation of haemoglobine syntheses in renal failure and oncology.
Topics: Anaphylaxis; Chronic Disease; Erythropoietin; Hemolysis; Humans; Iron Overload; Shock, Septic; Transfusion Reaction
PubMed: 12180032
DOI: No ID Found -
Assessment of human leukocyte antigen immunogenicity: current methods, challenges and opportunities.Current Opinion in Organ Transplantation Aug 2018Donor-recipient human leukocyte antigen (HLA) matching improves outcomes after solid-organ transplantation, but current assessment of HLA incompatibility is inadequate... (Review)
Review
PURPOSE OF REVIEW
Donor-recipient human leukocyte antigen (HLA) matching improves outcomes after solid-organ transplantation, but current assessment of HLA incompatibility is inadequate as it does not consider the relative immunogenicity of individual HLA mismatches. In this article, we review existing strategies for assessing HLA immunogenicity and discuss current challenges and future opportunities in this field.
RECENT FINDINGS
Current HLA immunogenicity algorithms focus primarily on the humoral component of the alloimmune response and aim to determine a measure of 'dissimilarity' between donor and recipient HLA. This can be achieved by deriving information from comparison of donor and recipient HLA at the amino acid sequence, structural and/or the physicochemical level, accounting for both B-cell and T-cell pathways of alloreactivity. Substantial evidence now supports the superiority of this molecular definition of HLA incompatibility, over conventional enumeration of HLA antigenic differences, for assessing the risk of humoral alloimmunity and for predicting graft outcomes after transplantation.
SUMMARY
Significant progress has been made in developing computational HLA immunogenicity algorithms that offer exciting opportunities for a more rational approach to determining the degree of donor-recipient HLA incompatibility and to defining HLA-related immunological risk. A number of challenges now need to be overcome to enable their implementation into clinical practice.
Topics: HLA Antigens; Histocompatibility; Histocompatibility Testing; Humans; Organ Transplantation; Tissue Donors; Transplantation Immunology
PubMed: 29870434
DOI: 10.1097/MOT.0000000000000544 -
Trends in Molecular Medicine Mar 2022Humoral alloimmunity of organ transplant recipient to donor can lead to antibody-mediated rejection (ABMR), causing thousands of organ transplants to fail each year... (Review)
Review
Humoral alloimmunity of organ transplant recipient to donor can lead to antibody-mediated rejection (ABMR), causing thousands of organ transplants to fail each year worldwide. However, the mechanisms of adaptive immune cell responses at the basis of humoral alloimmunity have not been entirely understood. In this review, we discuss how recent investigations have uncovered the key contributions of T follicular helper (T and B cells and their coordinated actions in driving donor-specific antibody generation and immune progression towards ABMR. We show how recognition of the role of T-B cell interactions may allow the elaboration of improved clinical strategies for immune monitoring and the identification of novel therapeutic targets to tackle ABMR that will ultimately improve organ transplant survival.
Topics: Antibodies; Graft Rejection; Graft Survival; Humans; Immunity, Humoral; Organ Transplantation
PubMed: 35093288
DOI: 10.1016/j.molmed.2022.01.002 -
Frontiers in Immunology 2022Passive immunization with anti-D can prevent maternal alloimmunization to RhD thereby preventing hemolytic disease of the fetus and newborn. Unexpectedly, anti-D fails...
Passive immunization with anti-D can prevent maternal alloimmunization to RhD thereby preventing hemolytic disease of the fetus and newborn. Unexpectedly, anti-D fails in some cases and some monoclonal anti-D preparations paradoxically enhances alloimmunization. The underlying mechanisms modulating humoral alloimmunization by anti-D are unknown. We previously reported that IgG antibody subclasses differentially regulate alloimmunity in response to red blood cell (RBC) transfusions in a mouse model; in particular, IgG2c significantly enhanced RBC alloantibody responses. Initial mechanistic studies revealed that IgG2c:RBC immune complexes were preferentially consumed by the splenic dendritic cell (DC) subsets that play a role in RBC alloimmunization. The deletion of activating Fc-gamma receptors (FcγRs) (i.e., FcγRI, FcγRIII, and FcγRIV) on DCs abrogated IgG2c-mediated enhanced alloimmunization. Because DCs express high levels of FcγRIV, which has high affinity for the IgG2c subclass, we hypothesized that FcγRIV was required for enhanced alloimmunization. To test this hypothesis, knockout mice and blocking antibodies were used to manipulate FcγR expression. The data presented herein demonstrate that FcγRIV, but not FcγRI or FcγRIII, is required for IgG2c-mediated enhancement of RBC alloantibody production. Additionally, FcγRI is alone sufficient for IgG2c-mediated RBC clearance but not for increased alloimmunization, demonstrating that RBC clearance can occur without inducing alloimmunization. Together, these data, combined with prior observations, support the hypothesis that passive immunization with an RBC-specific IgG2c antibody increases RBC alloantibody production through FcRIV ligation on splenic conventional DCs (cDCs). This raises the question of whether standardizing antibody subclasses in immunoprophylaxis preparations is desirable and suggests which subclasses may be optimal for generating monoclonal anti-D therapeutics.
Topics: Anemia, Hemolytic, Autoimmune; Animals; Antibodies, Blocking; Antigen-Antibody Complex; Immunoglobulin G; Isoantibodies; Mice; Mice, Knockout
PubMed: 36189253
DOI: 10.3389/fimmu.2022.972723 -
The Cochrane Database of Systematic... Sep 2015During pregnancy, a Rhesus negative (Rh-negative) woman may develop antibodies when her fetus is Rhesus positive (Rh-positive). These antibodies may harm Rh-positive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
During pregnancy, a Rhesus negative (Rh-negative) woman may develop antibodies when her fetus is Rhesus positive (Rh-positive). These antibodies may harm Rh-positive babies.
OBJECTIVES
To assess the effects of antenatal anti-D immunoglobulin on the incidence of Rhesus D alloimmunisation when given to Rh-negative women without anti-D antibodies.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised trials in Rh-negative women without anti-D antibodies given anti-D after 28 weeks of pregnancy, compared with no treatment, placebo or a different regimen of anti-D.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
MAIN RESULTS
We included two trials involving over 4500 women, comparing anti-D prophylaxis with no anti-D during pregnancy in this review. Overall, the trials were judged to be at moderate to high risk of bias. The quality of the evidence for pre-specified outcomes was also assessed using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.In regards to primary review outcomes, there did not appear to be a clear difference in the risks of immunisation when women who received anti-D at 28 and 34 weeks' gestation were compared with women who were not given antenatal anti-D: risk ratio (RR) for incidence of Rhesus D alloimmunisation during pregnancy was 0.42 (95% confidence interval (CI) 0.15 to 1.17, two trials, 3902 women; GRADE: low quality evidence); at birth of a Rh-positive infant the RR was 0.42 (95% CI 0.15 to 1.17, two trials, 2297 women); and within 12 months after birth of a Rh-positive infant the average RR was 0.39 (95% CI 0.10 to 1.62, two trials, 2048 women; Tau²: 0.47; I²: 39%; GRADE: low quality evidence). Neither of the trials reported on incidence of Rhesus D alloimmunisation in subsequent pregnancies.Considering secondary outcomes, in one trial, women receiving anti-D during pregnancy were shown to be less likely to register a positive Kleihauer test (which detects fetal cells in maternal blood) in pregnancy (at 32 to 25 weeks) (RR 0.60, 95% CI 0.41 to 0.88; 1884 women; GRADE: low quality evidence) and at the birth of a Rh-positive infant (RR 0.60, 95% CI 0.46 to 0.79; 1189 women; GRADE: low quality evidence). No clear differences were seen for neonatal jaundice (RR 0.26, 95% CI 0.03 to 2.30; 1882 infants; GRADE: very low quality evidence). Neither of the trials reported on adverse effects associated with anti-D treatment.
AUTHORS' CONCLUSIONS
Existing studies do not provide conclusive evidence that the use of anti-D during pregnancy benefits either mother or baby in terms of incidence of Rhesus D alloimmunisation during the pregnancy or postpartum, or the incidence of neonatal morbidity (jaundice) (low to very low quality evidence). However women receiving anti-D may be less likely to register a positive Kleihauer test in pregnancy and at the birth of a Rh-positive infant (low quality evidence). Fewer women who receive anti-D during pregnancy may have Rhesus D antibodies in a subsequent pregnancy, with benefits for the baby, however this needs to be tested in studies of robust design.
Topics: Female; Humans; Immunologic Factors; Pregnancy; Pregnancy Trimester, Third; Randomized Controlled Trials as Topic; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 26334436
DOI: 10.1002/14651858.CD000020.pub3 -
Frontiers in Immunology 2017Over the past decade, antibody-mediated (humoral) rejection has been recognized as a common cause of graft dysfunction after organ transplantation and an important... (Review)
Review
Over the past decade, antibody-mediated (humoral) rejection has been recognized as a common cause of graft dysfunction after organ transplantation and an important determinant for graft loss. In humoral alloimmunity, T follicular helper (Tfh) cells play a crucial role, because they help naïve B cells to differentiate into memory B cells and alloantibody-producing plasma cells within germinal centers. In this way, they contribute to the induction of donor-specific antibodies, which are responsible for the humoral immune response to the allograft. In this article, we provide an overview of the current knowledge on the effects of immunosuppressive therapies on Tfh cell development and function, and discuss possible new approaches to influence the activity of Tfh cells. In addition, we discuss the potential use of Tfh cells as a pharmacodynamic biomarker to improve alloimmune-risk stratification and tailoring of immunosuppression to individualize therapy after transplantation.
PubMed: 29163552
DOI: 10.3389/fimmu.2017.01510 -
Transfusion Medicine and Hemotherapy :... Oct 2019Since almost 30 years, lung transplantation is a considerable therapeutic option in patients suffering from end-stage lung disease. Up to now, the impact of... (Review)
Review
Since almost 30 years, lung transplantation is a considerable therapeutic option in patients suffering from end-stage lung disease. Up to now, the impact of donor-specific antibodies directed against donor HLA (human leukocyte antigen) before and after transplantation is still a matter of debate. As histocompatibility testing is not required for each patient according to the current national guidelines and Eurotransplant recommendations for lung transplantation, each transplantation unit has to establish a local protocol together with the tissue typing laboratory how to implement an immunological risk assessment strategy for their patients while enabling access to transplantation. Desensitization regimens might help in case of highly alloimmunized patients waiting for urgent transplantation.
PubMed: 31832059
DOI: 10.1159/000502124 -
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