Section III. Other Useful Facts

Reid, Marion E.

doi:10.1016/b978-0-12-415849-8.00050-8

Cited by 5 publications

(14 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The blood bank work-up, however, was significant for a newly positive direct antiglobulin test (DAT) (polyspecific: 1+, anti-IgG: weak, anti-C3: negative, eluate: negative), and a new anti-McC a , which was considered not clinically significant and has not been reported to cause hemolysis ( Table 1 ). 9 She was started on a hydromorphone patient-controlled analgesia pump for pain management, and she was transfused two units of least incompatible (incompatibility was from the new anti-McC a ), ABO compatible (patient: B+), leukocyte-reduced, sickle negative, and antigen-matched (E-, Jk(b-), K-, S,- by serology, and C w - and Js(a-) by genotype) red blood cells (RBC), with no complications and an appropriate increase in hemoglobin to 7.4 g/dL. On her second day of admission (HD 2), her platelet count unexpectedly decreased to 61,000 cells/uL, and her count continued to decline through her hospitalization.…”

Section: Case Reportmentioning

confidence: 99%

A Fatal Case of Immune Hyperhemolysis with Bone Marrow Necrosis in a Patient with Sickle Cell Disease

et al. 2017

View full text Add to dashboard Cite

In patients with sickle cell disease, hyperhemolysis is a rare but life-threatening complication of transfusion. In this case report, we describe a 61 year-old woman with hemoglobin sickle cell (SC) disease and history of alloimmunization who developed hyperhemolysis associated with a transfusion. She was found to have a warm and a clinically-significant cold autoantibody. Severe anemia (Hb 2.7 g/dL) with reticulocytopenia and thrombocytopenia prompted a bone marrow biopsy, which demonstrated extensive bone marrow necrosis. Despite treatment, the bone marrow failure did not improve and the patient died on hospital day 38. This case illustrates the potential risks of transfusion in a patient with sickle cell disease, especially one with previous hemolytic reactions. While uncommon, hyperhemolysis can cause death, in this case by extensive bone marrow necrosis. In patients with sickle cell disease, judicious use of red cell transfusions with phenotypically-matched units can diminish, but never completely abrogate, the risks associated with transfusion.

show abstract

Section: Case Reportmentioning

confidence: 99%

A Fatal Case of Immune Hyperhemolysis with Bone Marrow Necrosis in a Patient with Sickle Cell Disease

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The most well-known example of this is RhD whose expression levels are highly variable and can range from 30 copies of surface RhD to over 30,000 copies depending on the D variant. 14 Other examples of RBC antigens that are present at different copy numbers/cells include GPA (300,000-1200,000), 15 GPB (30,000-250,000), 15 LU (1500-4000), 16 or KEL (3500-18,000). 16 Important work by Howe and Stack has suggested an inverse relationship between immunogenicity and the antigen density of human non-RhD blood group antigens.…”

Section: Introductionmentioning

confidence: 99%

“…14 Other examples of RBC antigens that are present at different copy numbers/cells include GPA (300,000-1200,000), 15 GPB (30,000-250,000), 15 LU (1500-4000), 16 or KEL (3500-18,000). 16 Important work by Howe and Stack has suggested an inverse relationship between immunogenicity and the antigen density of human non-RhD blood group antigens. 17 This is supported by murine studies using RBCs expressing high densities of KEL (KEL hi -RBCs) or the transgenic human glycophorin A antigen (hGPA), both of which upon transfusion induce only weak recipient responses or tolerance in the absence of adjuvants or inflammation.…”

Section: Introductionmentioning

confidence: 99%

Antigen‐specific IgG subclass composition in recipient mice can indicate the degree of red blood cell alloimmunization as well as discern between primary and secondary immunization

2023

View full text Add to dashboard Cite

Background: Despite the vast antigen disparity between donor and recipient red blood cells (RBCs), only 2%-6% of transfusion patients mount an alloantibody response. Recently, RBC antigen density has been proposed as one of the factors that can influence alloimmunization, however, there has been no characterization of the role of antigen density along with RBC dose in primary and secondary immunization. Study Design and Methods: To generate RBCs that express distinct antigen copy numbers, different quantities of hen egg lysozyme (HEL) were coupled to murine RBCs. The HEL-RBCs were subsequently transfused into recipient mice at different RBC doses and their HEL-specific IgM, IgG, and IgG subclass response was evaluated. Results: Productive immune responses could be generated through a high copy number antigen transfused at low RBC doses or a low copy number transfused at high RBC doses. Further, primary but submaximal humoral immunization predominantly induced the IgG2b and IgG3 subclasses. In contrast, a maximal primary immunization or a secondary immunization induced all four IgG subclasses.Discussion: Our results confirm the existence of an antigen threshold for productive immune responses but indicate that a high antigen copy number alone might not be enough to induce a response, but rather a combination of both antigen copy number and cell dosage may determine the outcome of immunization. Further, this study provides a proof of concept that the IgG subclass composition can be an indicator of the level of RBC alloimmunization as well as discern between primary and secondary immunization at least in this murine model.Abbreviations: ABC, antibody binding capacity; ANOVA, analysis of variance; BSA, bovine serum albumin; ELISA, enzyme-linked immunosorbent assay; FMH, fetomaternal hemorrhage; GPA, glycophorin A; GPB, glycophorin B; HDFN, hemolytic disease of the fetus and newborn; HEL, hen egg lysozyme; hGPA, human glycophorin A antigen; HOD, recombinant antigen comprised of hen egg lysozyme linked with ovalbumin peptide and human duffy protein;

show abstract

“…Blood group antigens can vary extensively in their copy number between individuals. This is most well known for RhD whose antigen density can range from approximately 30 surface copies to over 30,000 copies/RBC, 7 but it is also observed for a variety of other RBC antigens 8,9 . For human non‐RhD RBC antigens, an inverse relationship between immunogenicity and antigen density has been suggested 10 .…”

Section: Introductionmentioning

confidence: 92%

“…This is most well known for RhD whose antigen density can range from approximately 30 surface copies to over 30,000 copies/RBC, 7 but it is also observed for a variety of other RBC antigens. 8,9 For human non-RhD RBC antigens, an inverse relationship between immunogenicity and antigen density has been suggested. 10 Murine studies have provided further evidence of the impact of antigen density on the immune response by showing that low antigen densities as well as high antigen densities can lead to unresponsiveness or even tolerance in a variety of mouse models.…”

Section: Introductionmentioning

confidence: 99%

Antigen copy number and antibody dose can determine the outcome of erythrocyte alloimmunization inducing either antibody‐mediated immune suppression or enhancement in a murine model

2023

View full text Add to dashboard Cite

Background The administration of anti‐D for the prevention of hemolytic disease of the fetus and newborn is one of the most successful clinical uses of the phenomenon of antibody‐mediated immune suppression (AMIS). However, despite adequate prophylaxis, failures can still occur in the clinic and are poorly understood. Recently, the copy number of red blood cell (RBC) antigens has been shown to influence immunogenicity in the context of RBC alloimmunization; however, its influence on AMIS remains unexplored. Study Design and Methods RBCs expressing approximately 3,600 and approximately 12,400 copy numbers of surface‐bound hen egg lysozyme (HEL), named respectively HELmed‐RBCs and HELhi‐RBCs, and selected doses of a polyclonal HEL‐specific IgG were transfused into mice. Recipient HEL‐specific IgM, IgG, and IgG subclass responses were evaluated by ELISA. Results Antigen copy number affected the antibody dose required for AMIS induction with higher antigen copy numbers requiring larger doses of antibody. For instance, 5 μg of antibody caused AMIS for HELmed‐RBCs but not HELhi‐RBCs, while 20 μg induced significant suppression for both HEL‐RBCs. Overall, increasing amounts of the AMIS‐inducing antibody were associated with a more complete AMIS effect. In contrast, the lowest tested doses of the AMIS‐inducing IgG led to evidence of enhancement at the IgM and IgG levels. Discussion The results demonstrate that the relationship between antigen copy number and antibody dose can influence the outcome of AMIS. Further, this work suggests that the same antibody preparation can induce both AMIS and enhancement but that the outcome may depend on the quantitative interrelationship of antigen–antibody binding.

show abstract

Section III. Other Useful Facts

Cited by 5 publications

References 12 publications

A Fatal Case of Immune Hyperhemolysis with Bone Marrow Necrosis in a Patient with Sickle Cell Disease

A Fatal Case of Immune Hyperhemolysis with Bone Marrow Necrosis in a Patient with Sickle Cell Disease

Antigen‐specific IgG subclass composition in recipient mice can indicate the degree of red blood cell alloimmunization as well as discern between primary and secondary immunization

Antigen copy number and antibody dose can determine the outcome of erythrocyte alloimmunization inducing either antibody‐mediated immune suppression or enhancement in a murine model

Contact Info

Product

Resources

About