Recipient T and B Lymphocytes Dictate the Severity of Antibody-Mediated Transfusion-Related Acute Lung Injury (TRALI).
Bibliographic record
Abstract
Abstract Abstract 641 Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion and has been ranked as the leading cause of transfusion-related fatalities. The majority (approx. 80%) of TRALI reactions are associated with and probably initiated by donor alloantibodies recognizing recipient granulocytes and/or human leukocytes antigens (HLA). Nonetheless, many details of the immunopathogenesis of TRALI are unknown. Previous studies have shown that a murine anti-MHC (H-2Kd) class I antibody (clone 34-1-2s) can induce TRALI in mice (Looney et al J Clin Invest. 116:1615,2006) and we utilized this model in an attempt to understand the role that recipient lymphocytes might play in TRALI reactions. BALB/c (H-2d) mice were injected iv with titrations of 34-1-2s and body temperature, morbidity/mortality, pulmonary granulocyte accumulation and serum levels of MIP-2 (the murine analog of human neutrophil chemokine IL8) were measured at various time points. Results showed that when BALB/c mice were administered 34-1-2s, a significant drop (N=20) in rectal body temperature indicating shock occurred within 30 min post-infusion, with evidence of recovery beginning at 1 hour post-infusion. Visible signs of breathing difficulty were apparent but there was no mortality observed. A significant granulocyte accumulation (N=20) within the lungs was also observed by 30 min post-infusion, which continued on to the end of the experiment (2 hours post-infusion). Serum MIP-2 levels were also significantly elevated concurrently with the granulocyte accumulation. To determine the role of recipient lymphocytes on these responses, BALB/c mice with severe combined immunodeficiency (SCID; lacking T and B lymphocytes) were infused with 34-1-2s. Compared with the BALB/c recipients, the decreases in rectal temperatures in the SCID mice were significantly greater (N=18) and there was a 66% mortality rate (N=18) with symptoms of severe respiratory distress and tracheal edema with 30 minutes after infusion of 34-1-2s. In addition, there was a significantly greater accumulation of pulmonary granulocytes in the SCID mice at lower doses of 34-1-2s and the antibody stimulated the production of significantly higher serum levels of MIP-2. These findings were also seen in 34-1-2s-infused SCID mice that were first depleted of natural killer cells suggesting that NK cells play no role in the enhanced severity of the antibody-mediated TRALI reaction. Taken together, these results suggest that recipient T and B lymphocytes have a protective role in suppressing antibody-mediated TRALI reactions perhaps by modulating recipient chemokine production. They identify a potentially new recipient mechanism that controls the severity of antibody-mediated TRALI. Disclosures: No relevant conflicts of interest to declare.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".