Enzymatic removal of cell surface antigens as a route towards universal O type blood and organs
Bibliographic record
Abstract
Mammalian cell surfaces are coated in specific sugar structures, many of which function as antigens and are involved in cellular recognition. Important examples are the oligosaccharide A, B, and H antigens present on red blood cells that differentiate the A, B and O blood types. Enzymatic cleavage of the GalNAc and Gal residues from the cell surface would allow conversion of A and B red blood cells, respectively, to O type. Since Type O blood can be universally donated to patients with the same Rh factor, access to efficient enzymes would greatly broaden and simplify blood supply. We have sought such enzymes in metagenomic libraries derived from the human gut microbiome. Total DNA was extracted from feces samples, fragmented into pieces containing ~30‐40 genes (40‐50 kB) and transformed into E. coli. After picking colonies into 384 well plates we screened them for enzymes that can be used to remove the Gal or GalNAc residues that function as the antigenic determinants from A and B type red blood cells, thereby generating “universal” O type blood. A set of efficient enzymes of a new class has been identified and characterized and used to convert whole units of A blood to O. These enzymes work approximately 30 times faster than any previously characterized and with high specificity. Further, they function well in whole blood thus can be hopefully integrated into the current blood processing process. 1 These enzymes also function well on tissue surfaces and, when perfused through donated human A‐type lungs successfully cleared A‐antigen from surfaces exposed to the blood. Subsequent perfusion of the lungs with O‐type plasma to mimic an ABO‐incompatible transplant showed that antigen removal minimized antibody binding and antibody‐mediated injury relative to the control lung, thus may greatly temper the acute rejection phase. 2 This could allow expansion of ABO‐incompatible lung transplantations, leading to significant improvements in logistics and fairness of organ allocation. Rahfeld, P. et al. “An enzymatic pathway in the human gut microbiome that converts A to universal O‐type blood” (2019) Nature Microbiology 4, 1475‐1485. Wang et al Conversion of blood type A donor lungs into universal blood type lungs using ex vivo ABO enzymatic treatment” (2022) Science Translational Medicine In Press, Scheduled Feb 2022
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".