Fine Specificity of B-Cell Tolerance to Blood Group Antigens Following ABO-Incompatible (Aboi) Heart Transplantation
Bibliographic record
Abstract
Introduction: Histo-blood group ABH(O) ags are oligosaccharides present as glycolipids or glycoproteins. A, B or H epitopes are carried by 6 different internal carbohydrate backbones (type I-VI), forming antigenically distinct variants, each type differentially expressed in human tissues. In heart, only type II structures are expressed (on vascular endothelium) whereas red cells express type I-IV. Identifying natural antibody (ab) clones specific to these ABH epitopes may be important in the setting of ABOi transplantation. Our objectives were to 1) develop a diagnostic tool to detect abs specific to ABH epitopes on all 6 carbohydrate backbones and 2) characterize abs in volunteers and patients who received ABOi heart transplants as infants. Methods: Chemically synthesized A type I-VI, B type I-VI and H type I-VI were printed onto microarray slides; spot morphology and ags were confirmed by monoclonal abs to ABH ags. After initial optimization, plasma from different blood group individuals and patients were hybridized and bound IgM, IgG and IgA detected with fluorescently-labelled secondary abs. Slides were scanned with a microarray scanner and Mean Fluorescent Intensities (MFI) determined using Imagene software. Results: Subtype-specific IgM, IgG and IgA abs varied substantially amongst individuals with different blood groups as well as the same blood group. In infants who received ABOi transplants, abs to donor blood group ags were not detected against type II subtype (fig 1) compared to same blood type controls (fig 2). Immunohistochemistry studies on cardiac biopsies confirmed that only type II carbohydrates were expressed on endothelium.[Figure 1][Figure 2]Conclusions: This analysis demonstrates that infant recipients of ABOi transplants remain deficient in production of antibodies to A-ag expressed in the cardiac graft, despite detection of antibodies to irrelevant A-ag detected by agglutination assay. Thus the ABO-microarray is valuable for subtype-specific blood group abs relevant to the graft. This tool will allow enhanced safety of ABO-incompatible organ transplantation and improve study of mechanisms of tolerance and/or accommodation in the clinical setting. Microarray technology provides analysis of tiny sample volumes (< 5 ml plasma), and simultaneous characterization of all ab isotypes, invaluable when testing infants.
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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".