Immune complex binding by immunocamouflaged [poly(ethylene glycol)‐grafted] erythrocytes
Bibliographic record
Abstract
Immune complexes (IC) are constantly formed at low levels in normal individuals. In humans, the red blood cell (RBC) complement receptor 1 (CR1) plays the dominant role in the IC binding and clearance. Over the last several years, we have investigated the potential utility of immunocamouflaged (methoxypoly(ethylene glycol) [mPEG] grafted) RBC to attenuate the risk of alloimmunization. Because the grafted polymer nonspecifically camouflages membrane proteins, its effects on CR1 detection and IC binding were assessed. The dose dependent (0-2.5 mM) effects of activated mPEG (CmPEG, 5 kDa; and BTCmPEG, 5 and 20 kDa) on CR1 detection and the binding of artificially generated IC [C3b coated alkaline phosphatase and antialkaline phosphatase complexes] to control and pegylated RBC was investigated by flow cytometry. In contrast to selected non-ABO blood group antigens, grafted mPEG did not effectively camouflage CR1. Surprisingly, however, even very low grafting concentrations of mPEG (>or=0.3 mM) resulted in a >or=95% loss in IC binding. Further reductions in grafting concentration (0.15 and 0.03 mM mPEG) still yielded decreased IC binding of approximately 60 and 40%, respectively. Importantly, unactivated mPEG had minimal effects on IC binding. These data demonstrate that even small amounts of grafted mPEG interfere with the multivalent CR1-IC interaction necessary for high affinity IC binding, hence large volume transfusions of mPEG-RBC may be contraindicated in patients with pre-existing IC disease. Whether this concern is of clinical significance in healthy humans is less clear due to dilutional effects and the presence of secondary clearance pathways.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".