Did you mean: alloimmunization
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Biomedicines Jun 2024Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense... (Review)
Review
Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a dual role. In immunocompromised individuals, posttransplant malignancies pose a significant health concern, with DCs serving as vital players in immune responses against cancer cells. Both recipient- and donor-derived DCs play a critical role in the rejection process, infiltrating the transplanted organ and sustaining T-cell responses. The use of immunosuppressive drugs represents the predominant approach to control this immunological barrier in transplanted organs. Evidence has shed light on the immunopharmacology of these drugs and novel strategies for manipulating DCs to promote allograft survival. Therefore, comprehending the mechanisms underlying this intricate microenvironment and the effects of immunosuppressive therapy on DCs is crucial for developing targeted therapies to reduce graft failure rates. This review will delve into the fundamental immunobiology of DCs and provide a detailed exploration of their clinical significance concerning alloimmune responses and posttransplant malignancies.
PubMed: 38927447
DOI: 10.3390/biomedicines12061240 -
Transfusion Jun 2024
PubMed: 38924565
DOI: 10.1111/trf.17933 -
Journal of Cardiothoracic Surgery Jun 2024We previously demonstrated that the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statins) play an important role in the regulation of alloimmune responses....
Graft protective effects and donor-specific antibody suppression by CD4CD25Foxp3 regulatory T cell induced by HMG-CoA reductase inhibitor rosuvastatin in a murine heart transplant model.
BACKGROUND
We previously demonstrated that the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statins) play an important role in the regulation of alloimmune responses. However, little is known regarding the effects of statin on allograft protection or donor-specific antibodies (DSA). In this study, we investigated the graft-protective and immunomodulatory effects of rosuvastatin in a model of fully major histocompatibility complex-mismatched murine cardiac allograft transplantation.
METHODS
CBA mice underwent transplantation of C57BL/6 (B6) hearts and received 50 and 500 μg/kg/day of rosuvastatin from the day of transplantation until seven days after the completion of transplantation. To confirm the requirement for regulatory T cells (Tregs), we administered an anti-interleukin-2 receptor alpha antibody (PC-61) to rosuvastatin-treated CBA recipients. Additionally, histological and fluorescent staining, cell proliferation analysis, flow cytometry, and DSA measurements were performed.
RESULTS
CBA recipients with no treatment rejected B6 cardiac graft acutely (median survival time [MST], 7 days). CBA mice treated with 500 μg/kg/day of rosuvastatin prolonged allograft survival (MSTs, 77 days). Fluorescent staining studies showed that rosuvastatin-treated recipients had strong aggregation of CD4Foxp3 cells in the myocardium and around the coronary arteries of cardiac allografts two weeks after grafting. Flow cytometry studies performed two weeks after transplantation showed an increased number of splenic CD4CD25Foxp3 T cells in rosuvastatin-treated recipients. The addition of rosuvastatin to mixed leukocyte cultures suppressed cell proliferation by increasing the number of CD4CD25Foxp3 Tregs. Additionally, Tregs suppressed DSA production in rosuvastatin-treated recipients.
CONCLUSION
Rosuvastatin treatment may be a complementary graft-protective strategy for suppressing DSA production in the acute phase, driven by the promotion of splenic and graft-infiltrating CD4CD25Foxp3 Tregs.
Topics: Animals; Rosuvastatin Calcium; Heart Transplantation; T-Lymphocytes, Regulatory; Mice; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mice, Inbred C57BL; Mice, Inbred CBA; Graft Rejection; Graft Survival; Interleukin-2 Receptor alpha Subunit; Male; Forkhead Transcription Factors; Disease Models, Animal; Flow Cytometry
PubMed: 38918849
DOI: 10.1186/s13019-024-02888-4 -
Transplantation Direct Jul 2024Biomarkers that predict posttransplant alloimmunity could lead to improved long-term graft survival. Evaluation of the number of mismatched epitopes between donor and...
BACKGROUND
Biomarkers that predict posttransplant alloimmunity could lead to improved long-term graft survival. Evaluation of the number of mismatched epitopes between donor and recipient HLA proteins, termed molecular mismatch analysis, has emerged as an approach to classify transplant recipients as having high, intermediate, or low risk of graft rejection. When high-resolution genotypes are unavailable, molecular mismatch analysis requires algorithmic assignment, or imputation, of a high-resolution genotyping. Although imputation introduces inaccuracies in molecular mismatch analyses, it is unclear whether these inaccuracies would impact the clinical risk assessment for graft rejection.
METHODS
Using renal transplant patients and donors from our center, we constructed cohorts of surrogate donor-recipient pairs with high-resolution and low-resolution HLA genotyping that were racially concordant or discordant. We systemically assessed the impact of imputation on molecular mismatch analysis for cohorts of 180-200 donor-recipient pairs for each of 4 major racial groups. We also evaluated the effect of imputation for a racially diverse validation cohort of 35 real-world renal transplant pairs.
RESULTS
In the surrogate donor-recipient cohorts, imputation preserved the molecular mismatch risk category for 90.5%-99.6% of racially concordant donor-recipient pairs and 92.5%-100% of racially discordant pairs. In the validation cohort, which comprised 72% racially discordant pairs, we found that imputation preserved the molecular mismatch risk category for 97.1% of pairs.
CONCLUSIONS
Overall, these data demonstrate that imputation preserves the molecular mismatch risk assessment in the vast majority of cases and provides evidence supporting imputation in the performance of molecular mismatch analysis for clinical assessment.
PubMed: 38911277
DOI: 10.1097/TXD.0000000000001639 -
Cureus May 2024Fy3 is a high-prevalence red blood cell antigen of the Duffy (Fy) blood group system. Anti-Fy3 antibodies are rare and solely arise in individuals with a Duffy null...
Fy3 is a high-prevalence red blood cell antigen of the Duffy (Fy) blood group system. Anti-Fy3 antibodies are rare and solely arise in individuals with a Duffy null phenotype (Fy(a-b-)), which is a phenotype that mainly occurs in people of African descent. Clinically, anti-Fy3 antibodies can cause both acute and delayed hemolytic transfusion reactions in adults as well as hemolytic disease in fetuses and newborns. Here, we report the case of a 26-year-old male with sickle cell disease (SCD) and a history of anti-E alloantibodies, who was admitted to the hospital with a vaso-occlusive crisis (VOC) and associated low hemoglobin (Hb) level. For the latter he received one unit of antigen-matched and crossmatch-compatible packed red blood cells (pRBCs) without complications. Ten days later the patient was readmitted with a further VOC and associated low Hb level, again requiring a red cell transfusion. However, no crossmatch-compatible pRBCs could be identified. Laboratory testing demonstrated pan-reactivity with additional reference testing demonstrating the presence of anti-E, anti-Fy3 and anti-Jk alloantibodies. This case highlights the diagnostic and therapeutic challenges associated with blood transfusion in SCD patients with rare alloimmunization profiles.
PubMed: 38910632
DOI: 10.7759/cureus.60939 -
Immunohematology Jun 2024Anti-f is produced by exposure to the compound antigen ce (f) on red blood cells (RBCs), expressed when both c and e are present on the same protein ( position)....
Anti-f is produced by exposure to the compound antigen ce (f) on red blood cells (RBCs), expressed when both c and e are present on the same protein ( position). Although anti-f was discovered in 1953, there are few cases reported worldwide because the presence of anti-f is often masked by anti-c or anti-e and is not generally found as a single antibody. In the present case, anti-f was identified by using three-cell screening and 11-cell identification panels. The identification of anti-f was further supported by additional testing, including (1) Rh antigen typing; (2) antibody identification panels (enzyme-treated panel [ficin] and an in-house-constructed Rh panel); (3) look-back and phenotyping of donor RBC units, which were responsible for alloimmunization; and (4) molecular testing of the patient's RBCs.
Topics: Humans; India; Isoantibodies; Erythrocytes; Blood Grouping and Crossmatching; Male; Female; Rh-Hr Blood-Group System
PubMed: 38910446
DOI: 10.2478/immunohematology-2024-008 -
Immunohematology Jun 2024The high number of D variants can lead to the unnecessary use of Rh immune globulin, overuse of D- RBC units, and anti-D allommunization. D variant prevalence varies...
The high number of D variants can lead to the unnecessary use of Rh immune globulin, overuse of D- RBC units, and anti-D allommunization. D variant prevalence varies among ethnic groups, and knowledge of the main variants present in a specific population, their behavior in serologic tests, and their impact on clinical practice is crucial to define the best serologic tests for routine use. The present study aimed to explore the serologic profile of D variants and to determine which variants are most associated with false-negative D typing results and alloimmunization. Donor samples were selected in two study periods. During the first period, D typing was performed on a semi-automated instrument in microplates, and weak D tests were conducted in tube or gel tests. In the second period, D typing was carried out using an automated instrument with microplates, and weak D tests were performed in solid phase. Samples from patients typed as D+ with anti-D were also selected. All samples were characterized by molecular testing. A total of 37 variants were identified. Discrepancies and atypical reactivity without anti-D formation were observed in 83.4 percent of the samples, discrepant D typing results between donations were seen in 12.3 percent, and D+ patients with anti-D comprised 4.3 percent. DAR1.2 was the most prevalent variant. Weak D type 38 was responsible for 75 percent of discrepant samples, followed by weak D type 11, predominantly detected by solid phase. Among the D variants related to alloimmunization, DIVa was the most prevalent, which was not recognized by serologic testing; the same was true for DIIIc. The results highlight the importance of selecting tests for donor screening capable of detecting weak D types 38 and 11, especially in populations where these variants are more prevalent. In pre-transfusion testing, it is crucial that D typing reagents demonstrate weak reactivity with DAR variants; having a serologic strategy to recognize DIVa and DIIIc is also valuable.
Topics: Humans; Rh-Hr Blood-Group System; Blood Donors; False Negative Reactions; Blood Grouping and Crossmatching; Female; Isoantibodies; Rho(D) Immune Globulin; Male
PubMed: 38910444
DOI: 10.2478/immunohematology-2024-007 -
Immunohematology Jun 2024This case report showcases an extraordinary collaboration to support the transfusion needs of a patient with a rare phenotype and long-standing anemia due to...
This case report showcases an extraordinary collaboration to support the transfusion needs of a patient with a rare phenotype and long-standing anemia due to gastrointestinal bleeding. This report describes the Immunohematology Reference Laboratory testing and logistics of rare blood provision over an 11-year period, as well as a summary of the hematologic, gastroenterologic, and surgical interventions. This case illustrates how a strong collaboration among the clinical team, laboratory, blood center, and the rare donor community facilitated successful management of this patient's anemia until the patient could receive life-changing treatment.
Topics: Humans; Blood Transfusion; Male; Anemia; Female; Gastrointestinal Hemorrhage; Blood Banks; Isoantibodies; Middle Aged
PubMed: 38910443
DOI: 10.2478/immunohematology-2024-011 -
Medicine Jun 2024Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated... (Observational Study)
Observational Study
Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated morbidities due to maternal ITP are unclear. The present study aimed to assess the neonatal outcomes of pregnant women with ITP. Fifty-five pregnant women with ITP and their babies, born between January/2013 and April/2021, were retrospectively reviewed. Maternal and neonatal thrombocytopenia cases other than ITP were excluded from the study. Physical examination, blood count, and cranial/abdominal ultrasonography findings of the newborns were recorded. Neonatal thrombocytopenia was defined as a platelet count < 150 × 109/L. Relationship between neonatal thrombocytopenia and maternal factors was investigated. Thrombocytopenia was detected in 17/55 babies (30.9%), and 8/17 (47.1%) had symptoms of bleeding, all but one being mild bleeding. There was a significant correlation between neonatal platelet counts of < 100 × 109/L and maternal splenectomy history. Incidence of moderate and severe thrombocytopenia was higher (statistically insignificant) in neonates of mothers with ITP. No significant correlation was determined between maternal and neonatal platelet counts. There was a weak insignificant correlation between platelet counts of neonates of mothers with or without thrombocytopenia. A significant correlation was found between the presence of splenectomy before delivery in the mother and a platelet count of < 100 × 109/L in the neonate. Moderate and severe thrombocytopenia was higher in neonates of mothers diagnosed with ITP before pregnancy and needed treatment during pregnancy and/or delivery, but the difference was insignificant. Close follow-up of babies born to mothers with ITP after birth is crucial since there is no significant prediction criterion for developing neonatal thrombocytopenia and associated morbidities.
Topics: Humans; Female; Retrospective Studies; Infant, Newborn; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Cross-Sectional Studies; Adult; Platelet Count; Pregnancy Complications, Hematologic; Thrombocytopenia, Neonatal Alloimmune; Splenectomy
PubMed: 38905433
DOI: 10.1097/MD.0000000000038587 -
Air Medical Journal 2024Recent years have seen increased discussion surrounding the benefits of damage control resuscitation, prehospital transfusion (PHT) of blood products, and the use of... (Review)
Review
Recent years have seen increased discussion surrounding the benefits of damage control resuscitation, prehospital transfusion (PHT) of blood products, and the use of whole blood over component therapy. Concurrent shortages of blood products with the desire to provide PHT during air medical transport have prompted reconsideration of the traditional approach of administering RhD-negative red cell-containing blood products first-line to females of childbearing potential (FCPs). Given that only 7% of the US population has blood type O negative and 38% has O positive, some programs may be limited to offering RhD-positive blood products to FCPs. Adopting the practice of giving RhD-positive blood products first-line to FCPs extends the benefits of PHT to such patients, but this practice does incur the risk of future hemolytic disease of the fetus and newborn (HDFN). Although the risk of future fetal mortality after an RhD-incompatible transfusion is estimated to be low in the setting of acute hemorrhage, the number of FCPs who are affected by this disease will increase as more air medical transport programs adopt this practice. The process of monitoring and managing HDFN can also be time intensive and costly regardless of the rates of fetal mortality. Air medical transport programs planning on performing PHT of RhD-positive red cell-containing products to FCPs should have a basic understanding of the pathophysiology, prevention, and management of hemolytic disease of the newborn before introducing this practice. Programs should additionally ensure there is a reliable process to notify receiving centers of potentially RhD-incompatible PHT because alloimmunization prophylaxis is time sensitive. Facilities receiving patients who have had PHT must be prepared to identify, counsel, and offer alloimmunization prophylaxis to these patients. This review aims to provide air medical transport professionals with an understanding of the pathophysiology and management of HDFN and provide a template for the early management of FCPs who have received an RhD-positive red cell-containing PHT. This review also covers the initial workup and long-term anticipatory guidance that receiving trauma centers must provide to FCPs who have received RhD-positive red cell-containing PHT.
Topics: Humans; Female; Air Ambulances; Rh-Hr Blood-Group System; Pregnancy; Erythrocyte Transfusion; Erythroblastosis, Fetal; Adult
PubMed: 38897700
DOI: 10.1016/j.amj.2024.03.012