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
Bibliographic record
Abstract
Abstract 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 HEL med ‐RBCs and HEL hi ‐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 HEL med ‐RBCs but not HEL hi ‐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.
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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 | 0.001 | 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 | 0.000 | 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".