Characterization of the Role of Antigen Copy Number in Red Blood Cell Alloimmunization
Bibliographic record
Abstract
Over 100 million red blood cell (RBC) units are transfused worldwide each year. Although a life saving intervention, RBC transfusion and the consequent exposure to foreign RBC antigens can lead to alloimmunization which significantly contributes to transfusion-related morbidity and mortality. RBC alloimmunization can also occur during pregnancy and cause hemolytic disease of the fetus and newborn (HDFN), a severe and potentially fatal neonatal disorder. The majority of HDFN cases are caused by maternal alloantibodies against the RhD antigen and can be effectively prevented through the administration of donor-derived Rhesus Immune Globulin (RhIg) which prevents the alloimmune response through a phenomenon known as antibody mediated immune suppression (AMIS). Despite its success, several limitations associated with RhIg’s donor-derived nature provide an incentive to replace RhIg with a recombinant alternative. Overall, a better understanding of the factors underlying RBC alloimmunization and AMIS could increase the safety of RBC transfusions, inform the development of a recombinant RhIg alternative, and extend the AMIS phenomenon to other HDFN-causing antigens. This thesis evaluated the role of antigen copy number, one of the proposed factors, on RBC alloimmunization and AMIS by designing a novel mouse model which allowed the alteration of the copy number of a model antigen. Results indicated that antigen copy number not only significantly influenced the magnitude of the murine immune response but also its IgG subclass composition. Further, the results showed that the antigen copy number significantly altered the requirements for AMIS induction and proposed that the quantitative interrelationship between antigen copy number and antibody dose can influence the induction of immune suppression or enhancement. Mechanistically, in vitro antigen loss rather than phagocytosis appeared to be more closely related to the observed in vivo AMIS effects. This combination of findings provides support for the conceptual premise that the copy number of an RBC antigen rather than its mere presence might determine the transfusion outcome. Further, they propose that fetal antigen copy numbers might need to be considered during RhIg administration and could provide one potential explanation for RhIg failures despite standard prophylaxis. Additionally, the findings provide intriguing information for the development of a recombinant RhIg alternative.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".