OA2‐AM23‐ST‐10 | Antibody‐Dependent Cellular Cytotoxicity is an Important Mechanism of Red Blood Cell Destruction in Antibody‐Mediated Hemolysis
Notice bibliographique
Résumé
The underlying cause for immune hemolysis by antibodies to human red cell antigens continues to be the subject of investigational studies on immune-mediated red cell destruction. The pathophysiology of antibody-mediated red blood cell (RBC) destruction has been thought to occur via extravascular phagocytosis by monocyte-macrophages. In some cases, rapid, including intravascular, hemolysis is present with no clear understanding of the mechanism. Antibody-dependent cellular cytotoxicity (ADCC) hemolysis mediated by natural killer cells (NK) is thought to occur in these cases, although this has not been thoroughly studied. We have used a monocyte monolayer assay (MMA) and NK-mediated ADCC to compare antibodies of different specificities to mediate either mechanism of RBC hemolysis. Examples of human, single specificity antibodies with a positive AHG-IAT reaction were tested for their phagocytic index using the MMA (>5 indicates a clinically significant antibody) and/or ADCC-mediated cytotoxicity (>2% specific cell death). For MMA, PBMCs were isolated from fresh whole blood or buffy coats and plated into chamber slides for evaluation of phagocytosis of opsonized antigen-positive RBCs. For ADCC, NK cells were purified using negative selection and specific cell lysis determined using a 51-Chromium release method of opsonized antigen-positive RBCs. Fifteen IgG alloantibodies, reactive by IAT, of the following specificities were examined: two anti-D, seven anti-E, two anti-K, two anti-Fya, and two anti-P1. Results indicate that 2/2 anti-K reacting 3+-mediated both significant MMA and ADCC results. One 4+ anti-D was positive by MMA and ADCC but one 1+ anti-D was positive with ADCC but not MMA. Out of seven anti-E samples, four reacting 3+ all gave insignificant results in the MMA, while two gave positive results in ADCC. Three anti-E reacting week to 2+ were negative by MMA but one of these was positive by ADCC. One 3+ anti-Fya was positive by MMA while one was positive by ADCC. Both anti-P1 were negative by MMA but one was positive by ADCC. Although a small sampling, we conclude that ADCC, in addition to phagocytosis, may contribute to immune hemolysis in patients who are actively hemolyzing. This is especially likely with anti-K. We also conclude that anti-E antibodies are usually benign, not clinically significant, not mediating either a significant MMA or ADCC result. We also find that ADCC can be positive without a positive MMA, especially with anti-D and anti-E. Thus, potential clinical significance of RBC antibodies my require both MMA and ADCC testing. ADCC likely plays a role in severe autoimmune hemolytic anemias and in hyperhemolysis in sickle cell patients, but we did not test these hypotheses. We are continuing to test additional antibodies to accumulate additional data to support our conclusions.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».