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British Journal of Haematology Feb 2022Red blood cell (RBC) alloimmunisation with anti-D and anti-K comprise the majority of cases of fetal haemolytic disease requiring intrauterine red cell transfusion...
Red blood cell (RBC) alloimmunisation with anti-D and anti-K comprise the majority of cases of fetal haemolytic disease requiring intrauterine red cell transfusion (IUT). Few studies have investigated which haematological parameters can predict adverse fetal or neonatal outcomes. The aim of the present study was to identify predictors of adverse outcome, including preterm birth, intrauterine fetal demise (IUFD), neonatal death (NND) and/or neonatal transfusion. We reviewed the records of all pregnancies alloimmunised with anti-K and anti-D, requiring IUT over 27 years at a quaternary fetal centre. We reviewed data for 128 pregnancies in 116 women undergoing 425 IUTs. The median gestational age (GA) at first IUT was significantly earlier for anti-K than for anti-D (24·3 vs. 28·7 weeks, P = 0·004). Women with anti-K required more IUTs than women with anti-D (3·84 vs. 3·12 mean IUTs, P = 0·036) and the fetal haemoglobin (Hb) at first IUT was significantly lower (51.0 vs. 70.5 g/l, P = 0·001). The mean estimated daily decrease in Hb did not differ between the two groups. A greater number of IUTs and a slower daily decrease in Hb (g/l/day) between first and second IUTs were predictive of a longer period in utero. Earlier GA at first IUT and a shorter interval from the first IUT until delivery predicted IUFD/NND. Earlier GA and lower Hb at first IUT significantly predicted need for phototherapy and/or blood product use in the neonate. In the anti-K group, a greater number of IUTs was required in women with a higher titre. Furthermore, the higher the titre, the earlier the GA at which an IUT was required in both groups. The rate of fall in fetal Hb between IUTs decreased, as the number of transfusions increased. Our present study identified pregnancies at considerable risk of an unfavourable outcome with anti-D and anti-K RBC alloimmunisation. Identifying such patients can guide pregnancy management, facilitates patient counselling, and can optimise resource use. Prospective studies can also incorporate these characteristics, in addition to laboratory markers, to further identify and improve the outcomes of these pregnancies.
Topics: Adult; Anemia, Hemolytic, Autoimmune; Blood Transfusion, Intrauterine; Erythrocytes; Female; Fetus; Humans; Pregnancy; Retrospective Studies; Rh Isoimmunization; Rho(D) Immune Globulin; Treatment Outcome
PubMed: 34862601
DOI: 10.1111/bjh.17956 -
The Journal of Maternal-fetal &... Nov 2020A Rho-incompatible pregnancy induces anemia in the fetus and can ultimately lead to fetal hydrops and intrauterine fetal death. A patient who had experienced recurrent...
A Rho-incompatible pregnancy induces anemia in the fetus and can ultimately lead to fetal hydrops and intrauterine fetal death. A patient who had experienced recurrent implantation failures following a first successful delivery finally succeeded in achieving a second pregnancy via the use of tacrolimus. The second pregnancy was Rho-incompatible. During the course of the pregnancy, the treatment with tacrolimus was continued because the patient's T helper type 1 (Th1) cell population remained at a high level following the achievement of pregnancy. The dose was increased during pregnancy because of the elevated Th1 cell count at 28-week gestation. Tacrolimus maintains a stable state of pregnancy while simultaneously suppressing the production of anti-D antibodies. Using tacrolimus, we succeeded in resolving the infertility and inhibition of antibody production in this case of an alloimmunized pregnancy.
Topics: Blood Transfusion, Intrauterine; Embryo Implantation; Female; Gestational Age; Humans; Hydrops Fetalis; Pregnancy; Tacrolimus
PubMed: 30821534
DOI: 10.1080/14767058.2019.1587406 -
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 -
Transfusion and Apheresis Science :... Oct 2020Anti-D immunoglobulin prophylaxis reduces the risk of RhD negative women becoming alloimmunised to the RhD antigen and is a major preventative strategy in reducing the... (Review)
Review
Anti-D immunoglobulin prophylaxis reduces the risk of RhD negative women becoming alloimmunised to the RhD antigen and is a major preventative strategy in reducing the burden of haemolytic disease of the fetus and newborn (HDFN). HDFN also arises from other maternal red cell antibodies, with the most clinically significant, after anti-D, being anti-K, anti-c and anti-E. Among the 39 human blood group systems advanced genomic technologies are still revealing novel or rare antigens involved in maternal alloimmunisation. Where clinically significant maternal antibodies are detected in pregnancy, non-invasive prenatal testing (NIPT) of cell-free fetal DNA provides a safe way to assess the fetal blood group antigen status. This provides information as to the risk for HDFN and thus guides management strategies. In many countries, NIPT fetal RHD genotyping as a diagnostic test using real-time PCR has already been integrated into routine clinical care for the management of women with allo-anti-D to assess the risk for HDFN. In addition, screening programs have been established to provide antenatal assessment of the fetal RHD genotype in non-alloimmunised RhD negative pregnant women to target anti-D prophylaxis to those predicted to be carrying an RhD positive baby. Both diagnostic and screening assays exhibit high accuracy (over 99 %). NIPT fetal genotyping for atypical (other than RhD) blood group antigens presents more challenges as most arise from a single nucleotide variant. Recent studies show potential for genomic and digital technologies to provide a personalised medicine approach with NIPT to assess fetal blood group status for women with other (non-D) red cell antibodies to manage the risk for HDFN.
Topics: Anemia, Hemolytic, Autoimmune; Erythroblastosis, Fetal; Female; Genetic Testing; Humans; Isoantibodies; Pregnancy; Prenatal Diagnosis
PubMed: 33115620
DOI: 10.1016/j.transci.2020.102947 -
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 -
Progress in Translational Regulatory T Cell Therapies for Type 1 Diabetes and Islet Transplantation.Endocrine Reviews Mar 2021Regulatory T cells (Tregs) have become highly relevant in the pathophysiology and treatment of autoimmune diseases, such as type 1 diabetes (T1D). As these cells are... (Review)
Review
Regulatory T cells (Tregs) have become highly relevant in the pathophysiology and treatment of autoimmune diseases, such as type 1 diabetes (T1D). As these cells are known to be defective in T1D, recent efforts have explored ex vivo and in vivo Treg expansion and enhancement as a means for restoring self-tolerance in this disease. Given their capacity to also modulate alloimmune responses, studies using Treg-based therapies have recently been undertaken in transplantation. Islet transplantation provides a unique opportunity to study the critical immunological crossroads between auto- and alloimmunity. This procedure has advanced greatly in recent years, and reports of complete abrogation of severe hypoglycemia and long-term insulin independence have become increasingly reported. It is clear that cellular transplantation has the potential to be a true cure in T1D, provided the remaining barriers of cell supply and abrogated need for immune suppression can be overcome. However, the role that Tregs play in islet transplantation remains to be defined. Herein, we synthesize the progress and current state of Treg-based therapies in T1D and islet transplantation. We provide an extensive, but concise, background to understand the physiology and function of these cells and discuss the clinical evidence supporting potency and potential Treg-based therapies in the context of T1D and islet transplantation. Finally, we discuss some areas of opportunity and potential research avenues to guide effective future clinical application. This review provides a basic framework of knowledge for clinicians and researchers involved in the care of patients with T1D and islet transplantation.
Topics: Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Islets of Langerhans Transplantation; T-Lymphocytes, Regulatory
PubMed: 33247733
DOI: 10.1210/endrev/bnaa028 -
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 -
British Journal of Haematology Jul 2022Most cases of fetal and neonatal thrombocytopenia (FNAIT) are caused by maternal anti-human platelet antigen-1a antibodies (anti-HPA-1a). Anti-HPA-5b antibodies are the... (Review)
Review
Most cases of fetal and neonatal thrombocytopenia (FNAIT) are caused by maternal anti-human platelet antigen-1a antibodies (anti-HPA-1a). Anti-HPA-5b antibodies are the second most common antibodies in suspected FNAIT cases. Given the high prevalence of anti-HPA-5b antibodies in pregnant women delivering healthy newborns, the association with FNAIT may be coincidental. This review of the literature related to FNAIT using the MEDLINE database was conducted according to PRISMA guidelines. A retrospective analysis of a single-centre cohort of 817 suspected FNAIT cases was conducted. The pooled prevalence of anti-HPA-5b antibodies in unselected pregnant women of European descent was 1.96% (n = 3113), compared with 3.4% (n = 5003) in women with suspected FNAIT. We found weak evidence that a small proportion of pregnant women presenting with anti-HPA-5b antibodies will give birth to a newborn with mild thrombocytopenia. The neonatal platelet counts were not different between suspected FNAIT cases (n = 817) with and without maternal anti-HPA-5b antibodies. The prevalence of maternal anti-HPA-5b antibodies was not different between neonates with intracranial haemorrhage and healthy controls. The current experimental and epidemiological evidence does not support the hypothesis that anti-HPA-5b antibodies cause severe thrombocytopenia or bleeding complications in the fetus or newborn.
Topics: Antibodies; Antigens, Human Platelet; Female; Fetal Diseases; Fetus; Humans; Infant, Newborn; Infant, Newborn, Diseases; Integrin beta3; Platelet Count; Pregnancy; Prenatal Care; Retrospective Studies; Thrombocytopenia, Neonatal Alloimmune
PubMed: 35383895
DOI: 10.1111/bjh.18173 -
Transfusion Medicine Reviews Oct 2020Refractoriness to platelet transfusion is a common clinical problem encountered by the transfusion medicine specialist. It is well recognized that most causes of... (Review)
Review
Refractoriness to platelet transfusion is a common clinical problem encountered by the transfusion medicine specialist. It is well recognized that most causes of refractoriness to platelet transfusion are not a consequence of alloimmunization to human leukocyte, platelet-specific, or ABO antigens, but are a consequence of platelet sequestration and consumption. This review summarizes the clinical factors that result in platelet refractoriness and highlights recent data describing novel biological mechanisms that contribute to this clinical problem.
Topics: Blood Platelets; Humans; Platelet Count; Platelet Transfusion; Spleen; Splenomegaly; Thrombocytopenia; Treatment Failure
PubMed: 33129606
DOI: 10.1016/j.tmrv.2020.09.002