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Transfusion and Apheresis Science :... Feb 2020Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen... (Review)
Review
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen (HPA). These antibodies can cause intracranial hemorrhage (ICH) or other major bleeding resulting in lifelong handicaps or death. Optimal fetal care can be provided by timely identification of pregnancies at risk. However, this can only be done by routinely antenatal screening. Whether nationwide screening is cost-effective is still being debated. HPA-1a alloantibodies are estimated to be found in 1 in 400 pregnancies resulting in severe burden and fetal ICH in 1 in 10.000 pregnancies. Antenatal treatment is focused on the prevention of fetal ICH and consists of weekly maternal IVIg administration. In high-risk FNAIT treatment should be initiated at 12-18 weeks gestational age using high dosage and in standard-risk FNAIT at 20-28 weeks gestational age using a lower dosage. Postnatal prophylactic platelet transfusions are often given in case of severe thrombocytopenia to prevent bleedings. The optimal threshold and product for postnatal transfusion is not known and international consensus is lacking. In this review practical guidelines for antenatal and postnatal management are offered to clinicians that face the challenge of reducing the risk of bleeding in fetuses and infants affected by FNAIT.
Topics: Humans; Infant, Newborn; Thrombocytopenia, Neonatal Alloimmune
PubMed: 31974030
DOI: 10.1016/j.transci.2019.102704 -
Blood Transfusion = Trasfusione Del... Jul 2012Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality. Antibodies against human leucocyte antigens (HLA) and human...
BACKGROUND
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality. Antibodies against human leucocyte antigens (HLA) and human neutrophil antigens (HNA) are often detected in the implicated donors. We investigated the incidence and aetiology of TRALI in Lombardy. Moreover, we determined the rate of HLA and HNA alloimmunisation and the HNA genotype in a cohort of local blood donors.
MATERIALS AND METHODS
During a 2-year observational study in eight blood transfusion services, suspected TRALI cases were collected and characterised by means of HLA and HNA antibody screening of implicated donors, donor/recipient cross-matching and HLA/HNA molecular typing. In addition, 406 Italian donors were evaluated for alloimmunisation and in 102 of them HNA gene frequencies were determined.
RESULTS
Eleven cases were referred to the central laboratory, of whom three were diagnosed as having TRALI, seven as having possible TRALI and one as having transfusion-associated circulatory overload. Seven TRALI cases were immune-mediated whereas in three we did not find either alloantibodies in implicated donors or a positive reaction in the cross-match. The most frequently implicated blood component was red blood cells (in 5 males and in 1 female), whereas four cases of TRALI were associated with transfusion of fresh-frozen plasma (in 3 females and in 1 male). The frequency of reported TRALI/possible TRALI cases was 1:82,000 for red blood cells and 1:22,500 for fresh-frozen plasma. No cases were observed for platelets. Overall, the frequency of HLA or HNA alloimmunisation in blood donors was 29% for females and 7% for males. The latter could be related, at least in part, to natural antibodies. HNA gene frequencies showed that HNA-1b is more frequent than HNA-1a in our sample of donors.
DISCUSSION
The recently adopted national policy to prevent TRALI, i.e. using only plasma donated by males, would have had a positive impact in our setting.
Topics: Acute Lung Injury; Adult; Aged; Aged, 80 and over; Blood Component Transfusion; Blood Donors; Child; Female; HLA Antigens; Humans; Isoantibodies; Isoantigens; Italy; Male; Middle Aged; Plasma; Retrospective Studies; Sex Factors
PubMed: 22395353
DOI: 10.2450/2012.0089-11 -
Frontiers in Immunology 2023Acute myeloid leukemia (AML) is one of the commonest hematologic disorders. Due to the high frequency of disease- or treatment-related thrombocytopenia, AML requires...
INTRODUCTION
Acute myeloid leukemia (AML) is one of the commonest hematologic disorders. Due to the high frequency of disease- or treatment-related thrombocytopenia, AML requires treatment with multiple platelet transfusions, which can trigger a humoral response directed against platelets. Some, but not all, AML patients develop an anti-HLA immune response after multiple transfusions. We therefore hypothesized that different immune activation profiles might be associated with anti-HLA alloimmunization status.
METHODS
We tested this hypothesis, by analyzing CD4+ T lymphocyte (TL) subsets and their immune control molecules in flow cytometry and single-cell multi-omics.
RESULTS
A comparison of immunological status between anti-HLA alloimmunized and non-alloimmunized AML patients identified differences in the phenotype and function of CD4+ TLs. CD4+ TLs from alloimmunized patients displayed features of immune activation, with higher levels of CD40 and OX40 than the cells of healthy donors. However, the most notable differences were observed in non-alloimmunized patients. These patients had lower levels of CD40 and OX40 than alloimmunized patients and higher levels of PD1. Moreover, the Treg compartment of non-alloimmunized patients was larger and more functional than that in alloimmunized patients. These results were supported by a multi-omics analysis of immune response molecules in conventional CD4+ TLs, Tfh circulating cells, and Tregs.
DISCUSSION
Our results thus reveal divergent CD4+ TL characteristics correlated with anti-HLA alloimmunization status in transfused AML patients. These differences, characterizing CD4+ TLs independently of any specific antigen, should be taken into account when considering the immune responses of patients to infections, vaccinations, or transplantations.
Topics: Humans; Blood Platelets; T-Lymphocytes, Helper-Inducer; CD4-Positive T-Lymphocytes; Thrombocytopenia; Anemia, Hemolytic, Autoimmune; CD40 Antigens; Leukemia, Myeloid, Acute
PubMed: 37701444
DOI: 10.3389/fimmu.2023.1165973 -
Archivum Immunologiae Et Therapiae... Aug 2016Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in... (Review)
Review
Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway.
Topics: Antigen Presentation; Antigens, Human Platelet; Blood Platelets; Europe; Female; Hemorrhage; Humans; Immunity, Cellular; Immunity, Humoral; Infant, Newborn; Integrin beta3; Isoantigens; Male; Neonatal Screening; Poland; Pregnancy; Rh-Hr Blood-Group System; Thrombocytopenia, Neonatal Alloimmune
PubMed: 26564154
DOI: 10.1007/s00005-015-0371-9 -
Orphanet Journal of Rare Diseases Oct 2006Foetal/neonatal alloimmune thrombocytopaenia (NAIT) results from maternal alloimmunisation against foetal platelet antigens inherited from the father and different from... (Review)
Review
Foetal/neonatal alloimmune thrombocytopaenia (NAIT) results from maternal alloimmunisation against foetal platelet antigens inherited from the father and different from those present in the mother, and usually presents as a severe isolated thrombocytopaenia in otherwise healthy newborns. The incidence has been estimated at 1/800 to 1/1000 live births. NAIT has been considered to be the platelet counterpart of Rh Haemolytic Disease of the Newborn (RHD). Unlike RHD, NAIT can occur during a first pregnancy. The spectrum of the disease may range from sub-clinical moderate thrombocytopaenia to life-threatening bleeding in the neonatal period. Mildly affected infants may be asymptomatic. In those with severe thrombocytopaenia, the most common presentations are petechiae, purpura or cephalohaematoma at birth, associated with major risk of intracranial haemorrhage (up to 20% of reported cases), which leads to death or neurological sequelae. Alloimmune thrombocytopaenia is more often unexpected and is usually diagnosed after birth. Once suspected, the diagnosis is confirmed by demonstration of maternal antiplatelet alloantibodies directed against a paternal antigen inherited by the foetus/neonate. Post-natal management involves transfusion of platelets devoid of this antigen, and should not be delayed by biological confirmation of the diagnosis (once the diagnosis is suspected), especially in case of severe thrombocytopaenia. Prompt diagnosis and treatment are essential to reduce the chances of death and disability due to haemorrhage. Due to the high rate of recurrence and increased severity of the foetal thrombocytopaenia in successive pregnancies, antenatal therapy should be offered. However, management of high-risk pregnancies is still a matter of discussion.
Topics: Antigens, Human Platelet; Autoantibodies; Female; Fetal Diseases; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Pregnancy; Thrombocytopenia
PubMed: 17032445
DOI: 10.1186/1750-1172-1-39 -
American Journal of Hematology Sep 2013Laboratory testing for immune-mediated thrombocytopenias involves identification and classification of antibodies present in patient sera or attached to patient... (Review)
Review
Laboratory testing for immune-mediated thrombocytopenias involves identification and classification of antibodies present in patient sera or attached to patient platelets. This article summarizes the available types of platelet antibody testing and applications in disorders such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, multiple platelet transfusion refractoriness, immune thrombocytopenia, and drug-induced thrombocytopenia.
Topics: Autoantibodies; Blood Platelets; Humans; Immunoassay; Infant, Newborn; Platelet Transfusion; Purpura, Thrombocytopenic; Quinine; Sulfonamides; Thrombocytopenia; Thrombocytopenia, Neonatal Alloimmune
PubMed: 23757218
DOI: 10.1002/ajh.23503 -
Diseases (Basel, Switzerland) Jan 2019Alloimmunisation to platelet antigens is not uncommon; a large number of females, having had pregnancies, developed antibodies to Human Leukocyte Antigen (HLA) moieties... (Review)
Review
Alloimmunisation to platelet antigens is not uncommon; a large number of females, having had pregnancies, developed antibodies to Human Leukocyte Antigen (HLA) moieties harboured on their foetuses' cells (inherited from the father(s)) that may conflict with further pregnancies and transfused Platelet Components occasionally. This is possible since platelets constitutionally express HLA class I molecules (though in copy numbers that consistently differ among individuals). Platelets also express HPA moieties that are variants of naturally expressed adhesion and aggregation molecules; HPA differences between mothers and foetuses and between donors and recipients explain alloimmune conflicts and consequences. Lastly, platelets express ABO blood group antigens, which are rarely immunising, however transfusion mismatches in ABO groups seem to be related to immunisation in other blood and tissue groups. Transfusion also brings residual leukocytes that may also immunise through their copious copy numbers of HLA class I (rarely class II on activated T lymphocytes, B cells, and dendritic cells). In addition, residual red blood cells in platelet concentrates may induce anti-red blood cell allo-antibodies. This short review aims to present the main mechanisms that are commonly reported in alloimmunisation. It also critically endeavours to examine paths to either dampen alloimmunisation occurrences or to prevent them.
PubMed: 30646515
DOI: 10.3390/diseases7010007 -
The Journal of Clinical Investigation Jun 2017Although gene-environment interactions have been investigated for many years to understand people's susceptibility to autoimmune diseases or cancer, a role for... (Review)
Review
Although gene-environment interactions have been investigated for many years to understand people's susceptibility to autoimmune diseases or cancer, a role for environmental factors in modulating alloimmune responses and transplant outcomes is only now beginning to emerge. New data suggest that diet, hyperlipidemia, pollutants, commensal microbes, and pathogenic infections can all affect T cell activation, differentiation, and the kinetics of graft rejection. These observations reveal opportunities for novel therapeutic interventions to improve graft outcomes as well as for noninvasive biomarker discovery to predict or diagnose graft deterioration before it becomes irreversible. In this Review, we will focus on the impact of these environmental factors on immune function and, when known, on alloimmune function, as well as on transplant fate.
Topics: Animals; Autoimmune Diseases; Gene-Environment Interaction; Graft Rejection; Humans; Neoplasms; T-Lymphocytes
PubMed: 28481225
DOI: 10.1172/JCI90596 -
Frontiers in Immunology 2020Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens,... (Review)
Review
Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens, costimulatory/inhibitory molecules, cytokines, growth factors, and functional microRNAs (miRNAs) that may modulate expression of recipient cell genes. As paracrine factors, neutrophil- and macrophage-derived EVs exert immunosuppressive and immune-stimulating effects on dendritic cells, respectively. Dendritic cell-derived EVs mediate alloantigen spreading and modulate antigen presentation to T lymphocytes. At systemic level, EVs exert pleiotropic effects on complement and coagulation. Depending on their biogenesis, they can amplify complement activation or shed complement inhibitors and prevent cell lysis. Likewise, endothelial- and platelet-derived EVs can exert procoagulant/prothrombotic effects and also promote endothelial survival and angiogenesis after ischemic injury. Kidney endothelial- and tubular-derived EVs play a key role in ischemia-reperfusion injury (IRI) and during the healing process; additionally, they can trigger rejection by inducing both alloimmune and autoimmune responses. Endothelial EVs have procoagulant/pro-inflammatory effects and can release sequestered self-antigens, generating a tissue-specific autoimmunity. Renal tubule-derived EVs shuttle pro-fibrotic mediators (TGF-β and miR-21) to interstitial fibroblasts and modulate neutrophil and T-lymphocyte influx. These processes can lead to peritubular capillary rarefaction and interstitial fibrosis-tubular atrophy. Different EVs, including those from mesenchymal stromal cells (MSCs), have been employed as a therapeutic tool in experimental models of rejection and IRI. These particles protect tubular and endothelial cells (by inhibition of apoptosis and inflammation-fibrogenesis or by inducing autophagy) and stimulate tissue regeneration (by triggering angiogenesis, cell proliferation, and migration). Finally, urinary and serum EVs represent potential biomarkers for delayed graft function (DGF) and acute rejection. In conclusion, EVs sustain an intricate crosstalk between graft tissue and innate/adaptive immune systems. EVs play a major role in allorecognition, IRI, autoimmunity, and alloimmunity and are promising as biomarkers and therapeutic tools in KT.
Topics: Cytokines; Endothelial Cells; Extracellular Vesicles; Immune System; Kidney; Kidney Diseases; Kidney Transplantation; Kidney Tubules; Macrophages; Mesenchymal Stem Cells; Reperfusion Injury; T-Lymphocytes; Transplants
PubMed: 32180768
DOI: 10.3389/fimmu.2020.00074 -
Medecine Sciences : M/S Jan 2009Fetomaternal alloimmunization with antenatal glomerulopathies (FMAIG) is a recently described alloimmune disorder, which results from the production of maternal... (Review)
Review
Fetomaternal alloimmunization with antenatal glomerulopathies (FMAIG) is a recently described alloimmune disorder, which results from the production of maternal antibodies that cross the placenta, bind to fetal glomerular podocytes, and mediate renal disease. The pathogenic antibodies are directed against CD10/neutral endopeptidase (NEP). The infant's mother is NEP-deficient and thus she becomes immunized during the first pregnancy against CD10/NEP expressed by placental cells. Because future pregnancies in CD10/NEP-immunized mothers are at high risk for the fetus, detection of anti-NEP antibodies in pregnant mothers and antigen-driven therapies including induction of tolerance, are urgently needed. This ideally requires identification of the pathogenic epitopes born by the antigen and specifically recognized by B- and T-cells. We have recently characterized such epitopes that will be used in diagnostic tests (ELISA) and for new therapeutic approaches based on peptide-specific immune intervention. For this purpose, we have developed an experimental model by crossing NEP/CD10-deficient female mice to wild-type males. The females develop an alloimmune reaction against NEP, which is a prerequisite for tolerance induction experiments. Although NEP/CD10 does not seem to be involved in common idiopathic forms of membranous nephropathy in the adult, alloimmune antibodies may be implicated in de novo membranous nephropathy that develop in the kidney graft and after alloimmune bone marrow transplantation.
Topics: Adoptive Transfer; Female; Fetal Diseases; Humans; Immunization; Kidney Diseases; Maternal-Fetal Exchange; Neprilysin; Placenta; Podocytes; Pregnancy
PubMed: 19154696
DOI: 10.1051/medsci/200925164