PMID- 28239987
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20230829
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 15
IP  - 5
DP  - 2017 May
TI  - Effects of alloantibodies to human leukocyte antigen on endothelial expression 
      and serum levels of thrombomodulin.
PG  - 1020-1031
LID - 10.1111/jth.13661 [doi]
AB  - Essentials The effect of alloantibodies on the endothelial expression of 
      thrombomodulin is unknown. Thrombomodulin was quantified in stimulated 
      endothelial cells and measured in serum samples. Anti-human leukocyte antigen 
      (HLA) I vs. II antibodies have different effects on thrombomodulin. Anti-HLA II 
      antibodies may promote a prothrombotic state and contribute to microangiopathy. 
      SUMMARY: Rationale Thrombomodulin (TBM) is an anticoagulant and anti-inflammatory 
      transmembrane protein expressed on endothelial cells. Donor-specific 
      alloantibodies, particularly those against human leukocyte antigen (HLA) class 
      II, are associated with microvascular endothelial damage in solid allografts. 
      Objective Our aim was to characterize the effects of anti-HLA antibodies on 
      endothelial expression of TBM, and in particular, the differential effects of 
      anti-HLA class I compared with those of anti-HLA class II. Methods We used human 
      glomerular microvascular endothelial cells to examine TBM expression on 
      anti-HLA-treated cells, and we tested sera from transplant recipients for soluble 
      TBM. Results We found that whereas membrane TBM expression increased in a 
      dose-dependent manner in the presence of anti-HLA class I antibodies, treatment 
      with anti-HLA class II led to minimal TBM expression on the endothelial surface 
      but to a cytosolic accumulation. Platelet adhesion studies confirmed the 
      functional impact of anti-HLA class II. Quantitative densitometry of the membrane 
      lysates further suggested that anti-HLA class II impairs TBM glycosylation. 
      Furthermore, we found a significant association between the presence of 
      circulating anti-HLA class II antibodies in transplant recipients and low serum 
      levels of TBM. Conclusion These results indicate that ligation of anti-HLA class 
      I and II antibodies produces different effects on the endothelial expression of 
      TBM and on serum levels of TBM in transplant recipients. Anti-HLA class II 
      antibodies may be associated with a prothrombotic state, which could explain the 
      higher occurrence of microangiopathic lesions in the allograft and the poor 
      outcomes observed in patients with these alloantibodies.
CI  - (c) 2017 International Society on Thrombosis and Haemostasis.
FAU - Beland, S
AU  - Beland S
AD  - Transplantation Unit, Renal Division, Department of Medicine, University Health 
      Center of Quebec, Faculty of Medicine, Laval University, Quebec City, QC, Canada.
FAU - Vallin, P
AU  - Vallin P
AD  - Transplantation Unit, Renal Division, Department of Medicine, University Health 
      Center of Quebec, Faculty of Medicine, Laval University, Quebec City, QC, Canada.
FAU - Desy, O
AU  - Desy O
AD  - Transplantation Unit, Renal Division, Department of Medicine, University Health 
      Center of Quebec, Faculty of Medicine, Laval University, Quebec City, QC, Canada.
FAU - Levesque, E
AU  - Levesque E
AD  - Hematology and Oncology Division, Department of Medicine, University Health 
      Center of Quebec, Faculty of Medicine, Laval University, Quebec City, QC, Canada.
FAU - De Serres, S A
AU  - De Serres SA
AD  - Transplantation Unit, Renal Division, Department of Medicine, University Health 
      Center of Quebec, Faculty of Medicine, Laval University, Quebec City, QC, Canada.
LA  - eng
GR  - KRI123890/Canadian Institutes of Health Research/International
GR  - 201309 PCL-134068/Canadian Institutes of Health Research/International
PT  - Comparative Study
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20170321
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (HLA Antigens)
RN  - 0 (Isoantibodies)
RN  - 0 (THBD protein, human)
RN  - 0 (Thrombomodulin)
SB  - IM
MH  - Cells, Cultured
MH  - Endothelial Cells/immunology/*metabolism
MH  - Glycosylation
MH  - Graft Rejection/blood/immunology
MH  - Graft Survival
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Isoantibodies/*immunology
MH  - Kidney Glomerulus/*blood supply
MH  - Kidney Transplantation/adverse effects
MH  - Microvessels/*immunology/*metabolism
MH  - Platelet Adhesiveness
MH  - Prospective Studies
MH  - Thrombomodulin/*blood
MH  - Time Factors
OTO - NOTNLM
OT  - alloantibodies
OT  - endothelial cells
OT  - thrombomodulin
OT  - thrombosis
OT  - transplantation
EDAT- 2017/02/28 06:00
MHDA- 2018/03/27 06:00
CRDT- 2017/02/28 06:00
PHST- 2016/08/10 00:00 [received]
PHST- 2017/02/28 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/02/28 06:00 [entrez]
AID - S1538-7836(22)00886-8 [pii]
AID - 10.1111/jth.13661 [doi]
PST - ppublish
SO  - J Thromb Haemost. 2017 May;15(5):1020-1031. doi: 10.1111/jth.13661. Epub 2017 Mar 
      21.