Antibody specific for the glycophorin <scp>A</scp> complex mediates intravenous immune globulin–resistant anemia in a murine model
Bibliographic record
Abstract
BACKGROUND: Therapy for patients with autoimmune hemolytic anemia (AHA) remains a major challenge. Patients with glycophorin A (GPA)-specific immunoglobulin G antibodies can have severe hemolysis, which may occur by mechanisms independent from traditional macrophage-dependent Fcγ receptor (FcγR)-mediated extravascular hemolysis. As intravenous immune globulin (IVIG) is known to display its beneficial effects in FcγR-mediated cytopenias, and IVIG responses in AHA are inconsistent at best, we sought to gain insight into the mechanism of anemia by a GPA complex-specific monoclonal antibody (TER119) in a mouse model of immune hemolytic anemia and evaluate the therapeutic effect of IVIG. STUDY DESIGN AND METHODS: The anemic effect of the TER119 antibody was studied in vitro by incubation of mouse RBC with the antibody and in vivo by infusing the antibody into normal mice versus mice genetically deficient for the Fc receptor γ chain (Fcγ), complement C3, mice naturally deficient in complement C5, and splenectomized mice. IVIG efficacy in anemia was determined by treating mice with an intensive IVIG dosing regimen. RESULTS: The TER119-mediated anemia was independent of classical FcγR-, C3-, and C5-dependent mechanisms, but occurred by a mechanism consistent with RBC agglutination. In accordance with agglutination, the presence of the spleen accelerated the anemia observed but anemia could still occur in splenectomized mice. IVIG did not significantly affect the induction of anemia by TER119. CONCLUSION: The mechanism of anemia induced by AHA-causing antibodies may be an important factor to consider in the response to therapy with IVIG.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 teacher head, 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".