PMID- 32485436
OWN - NLM
STAT- MEDLINE
DCOM- 20200904
LR  - 20200904
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 124
DP  - 2020 Aug
TI  - A complement-mediated rat xenotransfusion model of platelet refractoriness.
PG  - 9-17
LID - S0161-5890(20)30349-7 [pii]
LID - 10.1016/j.molimm.2020.05.008 [doi]
AB  - BACKGROUND: Platelet refractoriness remains a challenging clinical dilemma 
      although significant advancements have been made in identifying human leukocyte 
      antigen (HLA) matched or HLA compatible units. Antiplatelet antibodies are the 
      major risk factor for immune-mediated platelet refractoriness, yet the role of 
      antibody-initiated complement-mediated platelet destruction remains poorly 
      understood. STUDY DESIGN AND METHODS: Human complement-mediated opsonization and 
      killing of platelets was assayed ex vivo using antibody-sensitized human 
      platelets incubated with complement-sufficient human sera. A new animal model of 
      platelet refractoriness utilizing Wistar rats transfused with human platelets is 
      described. RESULTS: Human platelets sensitized with anti-platelet antibodies were 
      rapidly opsonized with iC3b upon incubation in human sera. This opsonization 
      could be completely blocked with a classical pathway complement inhibitor, 
      PA-dPEG24. Complement activation decreased platelet viability, which was also 
      reversible with complement inhibitor PA-dPEG24. A new rat model of platelet 
      refractoriness was developed that demonstrated some platelet removal from the 
      blood stream was complement mediated. CONCLUSIONS: Complement activation 
      initiated by anti-platelet antibodies leads to complement opsonization and 
      decreased platelet viability. A new rat model of platelet refractoriness was 
      developed that adds a new tool for elucidating the mechanisms of platelet 
      refractoriness.
CI  - Copyright (c) 2020. Published by Elsevier Ltd.
FAU - Enos, Adrianne I
AU  - Enos AI
AD  - Department of Pediatrics, Eastern Virginia Medical School, 700 West Olney Road, 
      Norfolk, VA 23507, USA. Electronic address: aenos@realtals.com.
FAU - Hair, Pamela S
AU  - Hair PS
AD  - Department of Pediatrics, Eastern Virginia Medical School, 700 West Olney Road, 
      Norfolk, VA 23507, USA. Electronic address: phair@realtals.com.
FAU - Krishna, Neel K
AU  - Krishna NK
AD  - Department of Pediatrics, Eastern Virginia Medical School, 700 West Olney Road, 
      Norfolk, VA 23507, USA; Department of Microbiology and Molecular Cell Biology, 
      Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, 
      USA. Electronic address: krishnnk@evms.edu.
FAU - Cunnion, Kenji M
AU  - Cunnion KM
AD  - Department of Pediatrics, Eastern Virginia Medical School, 700 West Olney Road, 
      Norfolk, VA 23507, USA; Children's Specialty Group, 811 Redgate Avenue, Norfolk, 
      VA 23507, USA; Children's Hospital of The King's Daughters, 601 Children's Lane, 
      Norfolk, VA 23507, USA; Department of Microbiology and Molecular Cell Biology, 
      Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, 
      USA. Electronic address: cunniokm@evms.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200530
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Isoantibodies)
SB  - IM
MH  - Animals
MH  - Blood Platelets/*immunology
MH  - Complement Activation/*immunology
MH  - Complement Pathway, Classical
MH  - *Disease Models, Animal
MH  - Humans
MH  - Isoantibodies/*immunology
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Transplantation, Heterologous
OTO - NOTNLM
OT  - Complement
OT  - PIC1
OT  - Platelet refractoriness
COIS- Declaration of Competing Interest Dr. Cunnion also serves as Chief Medical 
      Officer for ReAlta Life Sciences, Inc. Dr. Krishna also serves as Chief 
      Scientific Officer for ReAlta Life Sciences, Inc. The authors have no other 
      potential conflicts of interest to declare.
EDAT- 2020/06/03 06:00
MHDA- 2020/09/05 06:00
CRDT- 2020/06/03 06:00
PHST- 2019/12/04 00:00 [received]
PHST- 2020/04/22 00:00 [revised]
PHST- 2020/05/10 00:00 [accepted]
PHST- 2020/06/03 06:00 [pubmed]
PHST- 2020/09/05 06:00 [medline]
PHST- 2020/06/03 06:00 [entrez]
AID - S0161-5890(20)30349-7 [pii]
AID - 10.1016/j.molimm.2020.05.008 [doi]
PST - ppublish
SO  - Mol Immunol. 2020 Aug;124:9-17. doi: 10.1016/j.molimm.2020.05.008. Epub 2020 May 
      30.