Recipient T and B lymphocytes dictate the severity of antibody-mediated Transfusion-Related Acute Lung Injury (TRALI)

Fung, Yoke Lin, Kim, Michael, Speck, Edwin R., Freedman, John and Semple, John W. (2009). Recipient T and B lymphocytes dictate the severity of antibody-mediated Transfusion-Related Acute Lung Injury (TRALI). In: Blood. 51st Annual Meeting of the American Society of Hematology, New Orleans, LA, U.S.A., (266-266). 5-8 December 2009.

Author Fung, Yoke Lin
Kim, Michael
Speck, Edwin R.
Freedman, John
Semple, John W.
Title of paper Recipient T and B lymphocytes dictate the severity of antibody-mediated Transfusion-Related Acute Lung Injury (TRALI)
Conference name 51st Annual Meeting of the American Society of Hematology
Conference location New Orleans, LA, U.S.A.
Conference dates 5-8 December 2009
Proceedings title Blood   Check publisher's open access policy
Journal name Blood   Check publisher's open access policy
Place of Publication Washington, DC, U.S.A.
Publisher American Society of Hematology
Publication Year 2009
Sub-type Published abstract
ISSN 0006-4971
Volume 114
Issue 22
Start page 266
End page 266
Total pages 1
Language eng
Formatted Abstract/Summary
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.
Copyright © 2009 by American Society of Hematology

Subjects 1102 Cardiovascular Medicine and Haematology
1103 Clinical Sciences
1114 Paediatrics and Reproductive Medicine
Keyword Transfusion-Related Acute Lung Injury
Recipient lymphocytes
T and B lymphocytes
Q-Index Code EX
Q-Index Status Provisional Code

Document type: Conference Paper
Collection: School of Medicine Publications
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Created: Wed, 22 Sep 2010, 09:46:06 EST