PMID- 30474857
OWN - NLM
STAT- MEDLINE
DCOM- 20190506
LR  - 20211204
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Print)
IS  - 0041-1132 (Linking)
VI  - 59
IP  - 1
DP  - 2019 Jan
TI  - Antibody-mediated immunosuppression can result from RBC antigen loss independent 
      of Fcgamma receptors in mice.
PG  - 371-384
LID - 10.1111/trf.14939 [doi]
AB  - BACKGROUND: Anti-RhD administration can prevent de novo anti-RhD formation 
      following RhD+ red blood cell (RBC) exposure, termed antibody-mediated 
      immunosuppression (AMIS). Recent studies suggest that AMIS may occur through 
      target antigen alterations, known as antigen modulation. However, studies suggest 
      that AMIS may occur independent of antigen modulation. In particular, AMIS to 
      RBCs that transgenically express the fusion hen egg lysozyme-ovalbumin-Duffy 
      (HOD) antigen have been shown to occur independent of activating Fcgamma receptors 
      (FcgammaRs) thought to be required for antigen modulation. Therefore, we sought to 
      determine the mechanism behind AMIS following HOD RBC exposure. STUDY DESIGN AND 
      METHODS: Following transfer of HOD RBCs into wild-type or FcgammaR-chain knockout 
      recipients in the presence or absence of monoclonal anti-hen egg lysozyme (HEL) 
      antibody, individually or in combination, HOD antigen levels and anti-HOD 
      antibody formation were examined. RESULTS: Our results demonstrate that anti-HEL 
      antibodies individually or in combination suppressed anti-HOD IgM, which 
      correlated with the rate of detectable decrease in HEL on HOD RBCs. Furthermore, 
      exposure to anti-HEL antibodies alone or in combination equally suppressed 
      anti-HOD IgG formation. Unexpectedly, combination or individual anti-HEL 
      antibodies induced AMIS and antigen modulation in an FcgammaR-independent manner. 
      Pre-exposure of HOD RBCs to anti-HEL antibodies reduced antigen levels and 
      suppressed anti-HOD antibody formation following HOD RBC exposure. CONCLUSION: 
      These results suggest that antibody-mediated antigen modulation may reflect a 
      mechanism of AMIS that can occur independent of activating FcgammaRs and may provide 
      a surrogate to identify antibodies capable of inducing AMIS against different RBC 
      antigens.
CI  - (c) 2018 AABB.
FAU - Mener, Amanda
AU  - Mener A
AD  - Center for Transfusion Medicine and Cellular Therapies, Department of Laboratory 
      Medicine and Pathology, Emory University School of Medicine, Atlanta, Georgia.
FAU - Patel, Seema R
AU  - Patel SR
AD  - Center for Transfusion Medicine and Cellular Therapies, Department of Laboratory 
      Medicine and Pathology, Emory University School of Medicine, Atlanta, Georgia.
FAU - Arthur, Connie M
AU  - Arthur CM
AD  - Center for Transfusion Medicine and Cellular Therapies, Department of Laboratory 
      Medicine and Pathology, Emory University School of Medicine, Atlanta, Georgia.
FAU - Stowell, Sean R
AU  - Stowell SR
AD  - Center for Transfusion Medicine and Cellular Therapies, Department of Laboratory 
      Medicine and Pathology, Emory University School of Medicine, Atlanta, Georgia.
LA  - eng
GR  - T32 GM008169/GM/NIGMS NIH HHS/United States
GR  - P01 HL132819/HL/NHLBI NIH HHS/United States
GR  - R01 HL138656/HL/NHLBI NIH HHS/United States
GR  - R01 HL135575/HL/NHLBI NIH HHS/United States
GR  - DP5 OD019892/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181126
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/metabolism
MH  - Biotinylation
MH  - Blotting, Western
MH  - Erythrocytes/*metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Immunosuppression Therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, IgG/metabolism
PMC - PMC7145427
MID - NIHMS1575852
COIS- CONFLICT OF INTEREST The authors have disclosed no conflicts of interest.
EDAT- 2018/11/27 06:00
MHDA- 2019/05/07 06:00
PMCR- 2020/04/09
CRDT- 2018/11/27 06:00
PHST- 2018/01/12 00:00 [received]
PHST- 2018/04/17 00:00 [revised]
PHST- 2018/05/23 00:00 [accepted]
PHST- 2018/11/27 06:00 [pubmed]
PHST- 2019/05/07 06:00 [medline]
PHST- 2018/11/27 06:00 [entrez]
PHST- 2020/04/09 00:00 [pmc-release]
AID - 10.1111/trf.14939 [doi]
PST - ppublish
SO  - Transfusion. 2019 Jan;59(1):371-384. doi: 10.1111/trf.14939. Epub 2018 Nov 26.