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Record W4392900887 · doi:10.1093/bjs/znae046.009

O232: Enzymatic blood group conversion prevents complement activation in an ABO-incompatible model of human kidney transplantation

2024· article· en· W4392900887 on OpenAlexaff
Serena MacMillan, Sarah A. Hosgood, Peter Rahfeld, Léonie Walker-Panse, Spence S Macdonald, Jayachandran N. Kizhakkedathu, Stephen G. Withers, Michael L. Nicholson

Bibliographic record

VenueBritish journal of surgery · 2024
Typearticle
Languageen
FieldMedicine
TopicBlood groups and transfusion
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsABO blood group systemMedicineComplement systemPerfusionKidneyKidney transplantationTransplantationMachine perfusionBlood type (non-human)Classical complement pathwayStainingPathologyImmunologyInternal medicineAntibodyLiver transplantation

Abstract

fetched live from OpenAlex

Abstract Introduction Recently, enzymatic blood group conversion has been used to convert human kidneys from blood group A to universal blood group O using bacterial enzymes from Flavonifractor plautii. However, little is known about the functional consequences of antigen removal when a treated kidney is transplanted in an ABO-incompatible (ABOi) recipient. Here, we investigated classical complement activation during ABOi conditions in enzyme treated (ABOe) vs control human type A kidneys. Method Three biological pairs of type A human kidneys rejected for transplantation and offered for research were used in this study. One kidney per pair was treated with 1mg/L of FpGalNAc deacetylase and FpGalactosaminidase during 6hrs of hypothermic machine perfusion while the contralateral kidney was perfused without enzymes. Both kidneys were subsequently perfused for 4hrs in ABOi conditions using normothermic machine perfusion (10% AB serum; mouse anti-A IgM titre 1:128; type O red blood cells). Tissue-bound components of classical complement activation were assessed in pre- and post-perfusion biopsies. Results Following ABOi perfusion, control kidneys showed peritubular deposition of the classical complement component C1qA and further complement activation components C4d and C5b-9. The staining directly co-localised with regions of anti-A staining. In ABOe kidneys, no anti-A staining was observed, with no C1qA, C4d, or C5b-9 staining found in post-perfusion biopsies. Conclusions We have shown for the first time that ABOe kidneys do not activate the classical complement pathway in ABOi conditions. This work shows the potential of the enzymatic blood group conversion to evade hyperacute antibody-mediated rejection during renal transplantation.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.548
Threshold uncertainty score0.438

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.044
GPT teacher head0.287
Teacher spread0.243 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

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