-
Transfusion Medicine Reviews Oct 2020Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially serious bleeding condition in the fetus/newborn. FNAIT is usually considered as the... (Review)
Review
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially serious bleeding condition in the fetus/newborn. FNAIT is usually considered as the platelet counterpart of hemolytic disease of the fetus and newborn. In FNAIT, maternal alloantibodies against paternally inherited platelet antigens traverse the placenta and cause thrombocytopenia in the fetus/newborn. The most common and most serious cases of FNAIT among white people are caused by alloantibodies against the human platelet antigen 1a (HPA-1a), which is absent in 2.3% of women. Today, there is no screening for FNAIT, and for this reason, FNAIT is not suspected until an otherwise healthy child, born at term, presents with thrombocytopenia. Clinical management of subsequent pregnancies at risk of FNAIT is mostly based on the obstetric history. During the last 5 decades, hemolytic disease of the fetus and newborn caused by antibodies against RhD has successfully been prevented by administration of hyperimmune anti-D IgG drug products to RhD-negative women after delivery of an RhD-positive child. Similarly, a hyperimmune anti-HPA-1a IgG (NAITgam) is under development for the prevention of HPA-1a immunization and FNAIT. If NAITgam becomes licensed for FNAIT prophylaxis and national health authorities decide to include FNAIT screening in their antenatal health care programs, it will be necessary to improve today's tools for assessing the risk of FNAIT. Although the primary risk factor for HPA-1a immunization is platelet type HPA-1bb, not all HPA-1a-negative women develop anti-HPA-1a. The women who are HLA-DRB3:01:01 negative (72%) only rarely develop anti-HPA-1a, and for those few who become HPA-1a immunized, it is quite rare to have a child with severe thrombocytopenia. Determination of fetal HPA-1 type is important because 15% of HPA-1a-negative women will carry an HPA-1a-negative fetus and therefore not be at risk of FNAIT. The severity of FNAIT seems to be associated with the level of anti-HPA-1a. Hence, in Norway, for example, an Ab threshold of 3 IU/mL is used to distinguish between low- and high-risk pregnancies. The current review will discuss to what extent these analyses, as well as determination of subtypes of anti-HPA-1a (anti-β3, anti-αIIbβ3, and anti-αvβ3) and Fc core fucosylation of anti-HPA-1a IgG, can be used as risk stratification tools.
Topics: Antigens, Human Platelet; Biomarkers; Female; HLA-DRB3 Chains; Humans; Infant, Newborn; Integrin beta3; Isoantibodies; Pregnancy; Prenatal Care; Risk Assessment; Thrombocytopenia, Neonatal Alloimmune
PubMed: 33039264
DOI: 10.1016/j.tmrv.2020.09.004 -
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 -
Blood Nov 2000The development of hemolytic alloantibodies and erythrocyte autoantibodies complicates transfusion therapy in thalassemia patients. The frequency, causes, and prevention...
The development of hemolytic alloantibodies and erythrocyte autoantibodies complicates transfusion therapy in thalassemia patients. The frequency, causes, and prevention of this phenomena among 64 transfused thalassemia patients (75% Asian) were evaluated. The effect of red blood cell (RBC) phenotypic differences between donors (mostly white) and Asian recipients on the frequency of alloimmunization was determined. Additional transfusion and patient immune factors were examined. 14 (22%) of 64 patients (75% Asian) became alloimmunized. A mismatched RBC phenotype between the white population, comprising the majority of the donor pool, and that of the Asian recipients, was found for K, c, S, and Fyb antigens, which accounts for 38% of the alloantibodies among Asian patients. Patients who had a splenectomy had a higher rate of alloimmunization than patients who did not have a splenectomy (36% vs 12.8%; P =.06). Erythrocyte autoantibodies, as determined by a positive Coombs test, developed in 25% or 16 of the 64 patients, thereby causing severe hemolytic anemia in 3 of 16 patients. Of these 16, 11 antibodies were typed immunoglobulin G [IgG], and 5 were typed IgM. Autoimmunization was associated with alloimmunization and with the absence of spleen (44% and 56%, respectively). Transfused RBCs had abnormal deformability profiles, more prominent in the patients without a spleen, which possibly stimulated antibody production. Transfusion of phenotypically matched blood for the Rh and Kell (leukodepleted in 92%) systems compared to blood phenotypically matched for the standard ABO-D system (leukodepleted in 60%) proved to be effective in preventing alloimmunization (2.8% vs 33%; P =.0005). Alloimmunization and autoimmunization are common, serious complications in Asian thalassemia patients, who are affected by donor-recipient RBC antigen mismatch and immunological factors.
Topics: Adolescent; Adult; Anemia, Hemolytic; Asian People; Autoantibodies; Blood Donors; Blood Transfusion; Child; Child, Preschool; Erythrocyte Deformability; Erythrocytes; Female; Hemoglobin E; Hemoglobins, Abnormal; Humans; Incidence; Isoantibodies; Male; Phenotype; Pregnancy; Thalassemia; Transfusion Reaction; White People; alpha-Thalassemia
PubMed: 11071629
DOI: No ID Found -
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 -
Blood Reviews Nov 2013Notch signaling can regulate both hematopoietic progenitors and alloimmune T cells in the setting of allogeneic bone marrow or hematopoietic cell transplantation... (Review)
Review
Notch signaling can regulate both hematopoietic progenitors and alloimmune T cells in the setting of allogeneic bone marrow or hematopoietic cell transplantation (allo-HCT). Ex vivo culture of multipotent blood progenitors with immobilized Delta-like ligands induces supraphysiological Notch signals and can markedly enhance progenitor expansion. Infusion of Notch-expanded progenitors shortened myelosuppression in preclinical and early clinical studies, while accelerating T cell reconstitution in preclinical models. Notch also plays an essential role in vivo to regulate pathogenic alloimmune T cells that mediate graft-versus-host disease (GVHD), the most severe complication of allo-HCT. In mouse allo-HCT models, Notch inhibition in donor-derived T cells or transient blockade of Delta-like ligands after transplantation profoundly decreased GVHD incidence and severity, without causing global immunosuppression. These findings identify Notch in T cells as an attractive therapeutic target to control GVHD. In this review, we discuss these contrasting functions of Notch signaling with high translational significance in allo-HCT patients.
Topics: Animals; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Receptors, Notch; Signal Transduction; T-Lymphocytes
PubMed: 24050990
DOI: 10.1016/j.blre.2013.08.001 -
International Journal of Immunogenetics Jun 2020Humoral alloimmunity mediated by anti-human leucocyte antigen (HLA) antibodies is a major challenge in kidney transplantation and impairs the longevity of the... (Review)
Review
Humoral alloimmunity mediated by anti-human leucocyte antigen (HLA) antibodies is a major challenge in kidney transplantation and impairs the longevity of the transplanted organ. The immunological risk of an individual patient is currently mainly assessed by detection of HLA antibodies in the serum, which are produced by long-lived bone marrow-residing plasma cells. However, humoral alloimmunity is complex, and alloreactive memory B cells constitute an additional factor in the interplay of immune cells. These recirculating "silent" cells are responsible for the immunological recall response by differentiating into antibody-producing cells upon antigen re-encounter. Historically, due to the lack of appropriate and routinely applicable assays to determine the presence and HLA specificity of alloreactive memory B cells, their contribution to the humoral alloimmune response has clinically often been suspected but could not be determined. In this review, we give an overview of recent advances in techniques to detect alloreactive memory B cells and discuss their strengths and limitations. Furthermore, we summarize experiences with these techniques in alloimmunized individuals and transplant recipients, thereby emphasizing unmet needs to be addressed in future studies.
Topics: B-Lymphocytes; Graft Rejection; HLA Antigens; Histocompatibility; Humans; Immunity, Humoral; Immunologic Memory; Isoantibodies; Kidney Transplantation; Transplant Recipients; Transplants
PubMed: 32390325
DOI: 10.1111/iji.12493 -
Annals of Blood Dec 2020The high prevalence of red blood cell (RBC) alloantibodies in people with sickle cell disease (SCD) cannot be debated. Why people with SCD are so likely to form RBC...
The high prevalence of red blood cell (RBC) alloantibodies in people with sickle cell disease (SCD) cannot be debated. Why people with SCD are so likely to form RBC alloantibodies, however, remains poorly understood. Over the past decade, a better understanding of non-ABO blood group antigen variants has emerged; genetic diversity and the role this diversity plays in RBC alloimmunization is discussed elsewhere. Outside of antigen variants, the immune systems of people with SCD are known to be different than those of people without SCD. Some of these differences are due to effects of free heme, whereas others are impacted by hyposplenism. Descriptive studies of differences in white blood cell (WBC) subsets, platelet counts and function, and complement activation between people with SCD and race-matched controls exist. Studies comparing the immune systems of alloimmunized people with SCD to non-alloimmunized people with SCD to race-matched controls without SCD have uncovered differences in T-cell subsets, monocytes, Fcγ receptor polymorphisms, and responses to free heme. Studies in murine models have documented the role that recipient inflammation plays in RBC alloantibody formation, with human studies reporting a similar association. Murine studies have also reported the importance of type 1 interferon (IFNα/β), known to play a pivotal role in autoimmunity, in RBC alloantibody formation. The goal of this manuscript is to review existing data on factors influencing RBC alloantibody induction in people with SCD with a focus on inflammation and other immune system considerations, from the bench to the bedside.
PubMed: 33554044
DOI: 10.21037/aob-2020-scd-01 -
Transfusion Feb 2017Allogeneic blood transfusion can result in an immune response against major histocompatibility complex (MHC) antigens, potentially complicating future transfusions or...
BACKGROUND
Allogeneic blood transfusion can result in an immune response against major histocompatibility complex (MHC) antigens, potentially complicating future transfusions or transplants. We previously demonstrated that pathogen reduction of platelet-rich plasma (PRP) with riboflavin and ultraviolet light (UV+R) can prevent alloimmunization in mice. A similar pathogen-reduction treatment is currently under development for the treatment of whole blood using riboflavin and a higher dose of UV light. We sought to determine the effectiveness of this treatment in the prevention of alloimmunization.
STUDY DESIGN AND METHODS
BALB/cJ mice were transfused with untreated or UV+R-treated, allogeneic C57Bl/6J whole blood with or without leukoreduction. Mice were evaluated for donor-specific antibodies, ex vivo splenocyte cytokine responses, and changes in the frequency of regulatory T (T ) cells.
RESULTS
UV+R treatment blocked cytokine priming and reduced anti-MHC alloantibody responses to transfused whole blood. Leukoreduction reduced alloantibody levels in both the untreated and UV+R-treated groups. Mice transfused with UV+R-treated whole blood had reduced alloantibody and cytokine responses when subsequently transfused with untreated blood from the same donor type. This reduction in responses was not associated with increased T cells.
CONCLUSIONS
Pathogen reduction of whole blood with UV+R significantly reduces, but does not eliminate, the alloimmune response. Exposure to UV+R-treated whole blood transfusion does appear to induce tolerance to alloantigens, resulting in reduced anti-MHC alloantibody and cytokine responses to subsequent exposures to the same alloantigens. This tolerance does not appear to be driven by an increase in T cells.
Topics: Animals; Blood Transfusion; Disinfection; Histocompatibility Antigens; Isoantibodies; Mice; Mice, Inbred BALB C; Platelet-Rich Plasma; Riboflavin; T-Lymphocytes, Regulatory; Ultraviolet Rays
PubMed: 27859333
DOI: 10.1111/trf.13895 -
Biology of Blood and Marrow... Sep 2012Transforming growth factor (TGF)-β is a pleiotropic cytokine with widespread and profound effects on immune cells. Consequently, it has generated considerable interest... (Review)
Review
Transforming growth factor (TGF)-β is a pleiotropic cytokine with widespread and profound effects on immune cells. Consequently, it has generated considerable interest in relation to the immunologic outcomes after allogeneic hematopoietic cell transplantation. The TGF-β pathway has been shown to be an important modulator of alloimmunity, with direct consequences on graft-versus-host disease pathophysiology and graft-versus-tumor response. The TGF-β-related effects can be both beneficial and detrimental to the host, underscoring the complexity of TGF-β biology. This article reviews the evidence linking TGF-β to alloimmune responses in allogeneic hematopoietic cell transplantation and highlights foreseeable strategies that would maximize the beneficial effects of TGF-β pathway modulation on both graft-versus-host disease pathophysiology and the graft-versus-tumor effect.
Topics: Animals; Graft vs Host Disease; Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Humans; Immune Tolerance; Immunomodulation; Lymphocytes; Mice; Signal Transduction; Transforming Growth Factor beta; Transplantation, Homologous
PubMed: 22326303
DOI: 10.1016/j.bbmt.2012.01.020 -
Clinical Hematology International 2024Hematopoietic stem cell transplantation (HSCT) is a cornerstone of modern medical practice, and can only be performed safely and effectively with appropriate transfusion... (Review)
Review
Hematopoietic stem cell transplantation (HSCT) is a cornerstone of modern medical practice, and can only be performed safely and effectively with appropriate transfusion medicine support. Patients undergoing HSCT often develop therapy-related cytopenia, necessitating differing blood product requirements in the pre-, peri-, and post-transplant periods. Moreover, ensuring optimal management for patients alloimmunized to human leukocyte antigens (HLA) and/or red blood cell (RBC) antigens, as well as for patients receiving ABO-incompatible transplants, requires close collaboration with transfusion medicine and blood bank professionals. Finally, as updated transfusion guidelines and novel blood product modifications emerge, the options available to the transplant practitioner continue to expand. Herein, we detail contemporary blood transfusion and transfusion medicine practices for patients undergoing HSCT.
PubMed: 38817704
DOI: 10.46989/001c.94135