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Current Opinion in Organ Transplantation Feb 2016The purpose of this review is to provide a general update on recent developments in the immunobiology of IL-33 and IL-33-targeted immune cells. We also discuss emerging... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide a general update on recent developments in the immunobiology of IL-33 and IL-33-targeted immune cells. We also discuss emerging concepts regarding the potential role IL-33 appears to play in altering alloimmune responses mediating host-versus-graft and graft-versus-host alloresponses.
RECENT FINDINGS
Stromal cells and leukocytes display regulated expression of IL-33 and may actively or passively secrete this pleotropic cytokine. Type 2 innate lymphoid cells and a large proportion of tissue resident regulatory T cells (Treg) express membrane-bound suppressor of tumorigenicity 2 (ST2), the IL-33 receptor. Although Treg are appreciated suppressors of the inflammatory function of immune cells, both type 2 innate lymphoid cells and tissue resident Treg could play key roles in tissue repair and homeostasis. The functions of IL-33 in transplantation are poorly understood. However, like other disease models, the functions of IL-33 in alloimmunity appear to be quite pleiotropic. IL-33 is associated with immune regulation and graft protection in cardiac transplant settings. Yet, it is highly proinflammatory and stimulates lethal graft-versus-host disease through its capacity to stimulate type 1 immunity.
SUMMARY
Intensive studies on IL-33/ST2 signaling pathways and ST2 cell populations in solid organ and cell transplantation are warranted. A better understanding of this important pathway will provide promising therapeutic targets controlling pathogenic alloimmune responses, as well as potentially facilitating the function of regulatory and reparative immune cells posttransplantation.
Topics: Alarmins; Animals; Graft vs Host Disease; Humans; Interleukin-33; Lymphocytes; Signal Transduction
PubMed: 26709577
DOI: 10.1097/MOT.0000000000000265 -
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 -
Stem Cells Translational Medicine Mar 2014Blood transfusion is a common procedure in modern medicine, and it is practiced throughout the world; however, many countries report a less than sufficient blood supply.... (Review)
Review
Blood transfusion is a common procedure in modern medicine, and it is practiced throughout the world; however, many countries report a less than sufficient blood supply. Even in developed countries where the supply is currently adequate, projected demographics predict an insufficient supply as early as 2050. The blood supply is also strained during occasional widespread disasters and crises. Transfusion of blood components such as red blood cells (RBCs), platelets, or neutrophils is increasingly used from the same blood unit for multiple purposes and to reduce alloimmune responses. Even for RBCs and platelets lacking nuclei and many antigenic cell-surface molecules, alloimmunity could occur, especially in patients with chronic transfusion requirements. Once alloimmunization occurs, such patients require RBCs from donors with a different blood group antigen combination, making it a challenge to find donors after every successive episode of alloimmunization. Alternative blood substitutes such as synthetic oxygen carriers have so far proven unsuccessful. In this review, we focus on current research and technologies that permit RBC production ex vivo from hematopoietic stem cells, pluripotent stem cells, and immortalized erythroid precursors.
Topics: Antigens, CD; Biomarkers; Blood Transfusion; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cell Separation; Erythrocytes; Erythropoiesis; Feeder Cells; Hematopoietic Stem Cells; Humans; Isoantigens; Pluripotent Stem Cells; Reticulocytes
PubMed: 24361925
DOI: 10.5966/sctm.2013-0054 -
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 -
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 -
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 -
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 -
Blood Transfusion = Trasfusione Del... Jan 2022Alloimmunisation against blood products is an adverse event, causing time-consuming compatibility testing. Current literature has not yet identified the influence of... (Observational Study)
Observational Study
BACKGROUND
Alloimmunisation against blood products is an adverse event, causing time-consuming compatibility testing. Current literature has not yet identified the influence of treatment on the risk of alloimmunisation in patients with myelodysplastic syndromes (MDS).
MATERIALS AND METHODS
An observational, population-based study, using the HemoBase registry, was performed including all transfused patients who were diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands. Information about transfusion dates, types, and treatment regimens was collected from the health records. Blood products were matched for ABO and Rhesus D. The effect of disease-modifying treatment was estimated with incidence rates and a Cox time-dependent analysis.
RESULTS
233 patients were included in this study, with a median follow-up of 13.0 months. Alloimmunisation occurred in 21 patients (9.0%) and predominantly occurred early in follow-up. Three (5%) and 18 (11%) alloimmunisation events occurred in patients with and without disease-modifying treatment, respectively. The hazard ratio for alloimmunisation without treatment compared to during treatment was 2.7 (95% CI: 0.35-20.0), with incidence rates of 7.18 and 2.41 per 100 patient-years, respectively.
DISCUSSION
In a non-selected real-world population of MDS patients receiving blood transfusions, the percentage of patients with alloimmunisation was below 10%. The results of this study support the hypothesis that disease-modifying treatment affects the ability of the immune system to mount an antibody response to non-self blood group antigens.
Topics: Anemia, Hemolytic, Autoimmune; Blood Group Antigens; Blood Transfusion; Humans; Incidence; Myelodysplastic Syndromes
PubMed: 33370223
DOI: 10.2450/2020.0168-20 -
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