PMID- 31608454
OWN - NLM
STAT- MEDLINE
DCOM- 20200608
LR  - 20200608
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Linking)
VI  - 59
IP  - 11
DP  - 2019 Nov
TI  - Transfusion-related immunomodulation: gamma irradiation alters the effects of 
      leukoreduction on alloimmunization.
PG  - 3396-3404
LID - 10.1111/trf.15555 [doi]
AB  - BACKGROUND: Adverse events following blood transfusion include allosensitization 
      and generalized immunosuppression, collectively referred to as 
      transfusion-related immune modulation. We evaluated the immunological effects of 
      red blood cell (RBC) and platelet transfusions on alloantibody responses and on 
      immunoregulatory cells in nonimmunosuppressed patients undergoing cardiovascular 
      surgery. STUDY DESIGN AND METHODS: Patients were randomized to receive standard 
      unmodified (STD), leukoreduced (LR), or leukoreduced and gamma-irradiated (LRgamma) RBCs. 
      Patients received only apheresis platelets that were in-process LR and were 
      gamma-irradiated for the third arm. Nontransfused patients served as controls for the 
      effects of surgery itself on immunologic changes. Antibodies to HLA were assessed 
      with use of solid-phase assays. The effects of transfusion on adaptive and innate 
      immunity were evaluated by assessing T regulatory cells (Tregs) and invariant 
      natural killer T (iNKT) cells. RESULTS: LR of blood products reduced the 
      development of human leukocyte antigen (HLA) alloantibodies, but only in patients 
      without preexisting HLA antibodies. However, if LR blood products were 
      gamma-irradiated, HLA antibody production was not reduced. Compared to nontransfused 
      patients, recipients of STD or LR transfusions showed a significant increase in 
      CD4+CD25(hi) T cells expressing FoxP3 or CTLA4 and also of iNKT cells producing 
      interleukin-4. In contrast, recipients of LRgamma blood products showed markedly 
      lower increases in all three cellular assays. CONCLUSION: LR decreased HLA 
      alloantibody production in naive recipients, but did not reduce the 
      immunosuppressive effects of transfusion. LRgamma reduced immunosuppression and was 
      not associated with decreased HLA alloantibody production.
CI  - (c) 2019 AABB.
FAU - Nelson, Karen A
AU  - Nelson KA
AUID- ORCID: 0000-0001-7373-1566
AD  - Bloodworks Northwest, Seattle, Washington.
FAU - Aldea, Gabriel S
AU  - Aldea GS
AD  - Department of Surgery, Division of Cardiothoracic Surgery, University of 
      Washington, Seattle, Washington.
FAU - Warner, Paul
AU  - Warner P
AD  - Bloodworks Northwest, Seattle, Washington.
FAU - Latchman, Yvette
AU  - Latchman Y
AD  - Bloodworks Northwest, Seattle, Washington.
AD  - Silverback Therapeutics, Seattle, Washington.
FAU - Gunasekera, Devi
AU  - Gunasekera D
AD  - Bloodworks Northwest, Seattle, Washington.
AD  - Uniformed Services University of Health Sciences, Bethesda, Maryland.
FAU - Tamir, Ayala
AU  - Tamir A
AD  - Bloodworks Northwest, Seattle, Washington.
FAU - Gernsheimer, Terry
AU  - Gernsheimer T
AD  - Bloodworks Northwest, Seattle, Washington.
AD  - Division of Hematology, University of Washington School of Medicine, Seattle, 
      Washington.
AD  - Seattle Cancer Care Alliance, Seattle, Washington.
FAU - Bolgiano, Doug
AU  - Bolgiano D
AD  - Bloodworks Northwest, Seattle, Washington.
FAU - Slichter, Sherrill J
AU  - Slichter SJ
AD  - Bloodworks Northwest, Seattle, Washington.
AD  - Division of Hematology, University of Washington School of Medicine, Seattle, 
      Washington.
AD  - Seattle Cancer Care Alliance, Seattle, Washington.
LA  - eng
SI  - ClinicalTrials.gov/NCT00810810
GR  - 1 P50 HL081015/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20191013
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (HLA Antigens)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - *Blood Transfusion
MH  - *Gamma Rays
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - *Immune Tolerance
MH  - Isoantibodies/*blood
MH  - *Leukocyte Reduction Procedures
MH  - Natural Killer T-Cells/immunology
MH  - T-Lymphocytes, Regulatory/immunology
EDAT- 2019/10/15 06:00
MHDA- 2020/06/09 06:00
CRDT- 2019/10/15 06:00
PHST- 2019/01/23 00:00 [received]
PHST- 2019/08/21 00:00 [revised]
PHST- 2019/08/21 00:00 [accepted]
PHST- 2019/10/15 06:00 [pubmed]
PHST- 2020/06/09 06:00 [medline]
PHST- 2019/10/15 06:00 [entrez]
AID - 10.1111/trf.15555 [doi]
PST - ppublish
SO  - Transfusion. 2019 Nov;59(11):3396-3404. doi: 10.1111/trf.15555. Epub 2019 Oct 13.