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Recipient T and B Lymphocytes Dictate the Severity of Antibody-Mediated Transfusion-Related Acute Lung Injury (TRALI)
Abstract   Peer reviewed

Recipient T and B Lymphocytes Dictate the Severity of Antibody-Mediated Transfusion-Related Acute Lung Injury (TRALI)

Yoke Lin Fung, Michael Kim, Edwin R Speck, John Freedman and John W Semple
Blood, Vol.114(22)
American Society of Hematology (ASH) Annual Meeting, 51st (New Orleans, United States, 05-Dec-2009–08-Dec-2009)
2009
DOI: https://doi.org/10.1182/blood.V114.22.641.641
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https://doi.org/10.1182/blood.V114.22.641.641View
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Abstract

Cardiovascular Medicine and Haematology Clinical Sciences Paediatrics and Reproductive Medicine
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.

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