PMID- 23856214
OWN - NLM
STAT- MEDLINE
DCOM- 20131028
LR  - 20130716
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 32
IP  - 8
DP  - 2013 Aug
TI  - Pathologic classification of antibody-mediated rejection correlates with 
      donor-specific antibodies and endothelial cell activation.
PG  - 769-76
LID - S1053-2498(13)01275-8 [pii]
LID - 10.1016/j.healun.2013.05.012 [doi]
AB  - BACKGROUND: Humoral immune responses during heart transplantation may result in 
      antibody-mediated rejection (AMR), which is now taken into account on 
      endomyocardial biopsy (EMB) specimens and ranked according to the pathologic AMR 
      (pAMR) grades of the International Society for Heart and Lung Transplantation 
      classification. This classification might benefit from new immunohistological 
      markers and validation by others biomarkers, namely donor-specific antibodies 
      (DSA). METHODS: From the 293 protocol EMBs performed in 113 patients in our 
      institution during a 1-year period for this prospective study, 280 EMB specimens 
      were available with both histology and immunohistochemistry. C4d and labeling of 
      intravascular cells by cluster of differentiation (CD) 68 were performed on 
      paraffin sections. Available sera (n = 150) concomitant of EMB specimens were 
      tested for the presence of DSA. All of the pAMR+ EMB specimens, along with a set 
      of randomized pAMR0 EMB specimens, were immunolabeled for mammalian target of 
      rapamycin (mTOR) effectors, phosphorylated 70 S6-kinase (p70S6K) and 
      phosphorylated S6 ribosomal protein (pS6RP). RESULTS: AMR was diagnosed in 37 EMB 
      specimens (13.2%): 1 pAMR1(I+), 27 pAMR1(H+), and 9 pAMR2. The proportion of 
      DSA-positive EMB varied according to the pAMR grade, with pAMR0, pAMR1(H+), and 
      pAMR2 EMB presenting 17.6%, 77.3%, and 100% of DSA-positivity, respectively. 
      Among the 30 pAMR+ specimens with available DSA testing and the 30 pAMR0 
      randomized specimens, mTOR pathway immunohistochemistry showed endothelial cell 
      positivity for p70S6K in 17 pAMR+ EMB specimens (56.7%) and in 1 pAMR0 EMB 
      specimen (3.3%). pS6RP was detected in 8 pAMR+ EMB specimens (26.7%) and in 1 
      pAMR0 EMB specimen (3.3%). CONCLUSIONS: p70S6K and pS6RP immunohistochemistry 
      afford new markers of AMR on EMB specimens because their expression is correlated 
      with microcirculation inflammation and DSA. The correlation of DSA with pAMR 
      grade suggests that this grading system is valid.
CI  - Copyright (c) 2013 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Tible, Marion
AU  - Tible M
AD  - Universite Paris Descartes Medecine, Paris, France.
FAU - Loupy, Alexandre
AU  - Loupy A
FAU - Vernerey, Dewi
AU  - Vernerey D
FAU - Suberbielle, Caroline
AU  - Suberbielle C
FAU - Beuscart, Thibaut
AU  - Beuscart T
FAU - Cazes, Aurelie
AU  - Cazes A
FAU - Guillemain, Romain
AU  - Guillemain R
FAU - Amrein, Catherine
AU  - Amrein C
FAU - Pezzella, Veronique
AU  - Pezzella V
FAU - Fabiani, Jean-Noel
AU  - Fabiani JN
FAU - Nochy, Dominique
AU  - Nochy D
FAU - Hill, Gary
AU  - Hill G
FAU - Empana, Jean-Philippe
AU  - Empana JP
FAU - Jouven, Xavier
AU  - Jouven X
FAU - Charron, Dominique
AU  - Charron D
FAU - Bruneval, Patrick
AU  - Bruneval P
FAU - Duong Van Huyen, Jean-Paul
AU  - Duong Van Huyen JP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Antibodies)
SB  - IM
MH  - Adult
MH  - Antibodies/*immunology
MH  - Endothelial Cells/*immunology
MH  - Female
MH  - Graft Rejection/classification/*immunology/*pathology
MH  - Heart Transplantation/*immunology/*pathology
MH  - Humans
MH  - Male
MH  - Prospective Studies
MH  - Tissue Donors
OTO - NOTNLM
OT  - antibody-mediated rejection
OT  - donor-specific antibodies
OT  - endomyocardial biopsy
OT  - heart transplantation
OT  - microcirculation inflammation
OT  - pAMR
EDAT- 2013/07/17 06:00
MHDA- 2013/10/29 06:00
CRDT- 2013/07/17 06:00
PHST- 2013/01/08 00:00 [received]
PHST- 2013/05/05 00:00 [revised]
PHST- 2013/05/23 00:00 [accepted]
PHST- 2013/07/17 06:00 [entrez]
PHST- 2013/07/17 06:00 [pubmed]
PHST- 2013/10/29 06:00 [medline]
AID - S1053-2498(13)01275-8 [pii]
AID - 10.1016/j.healun.2013.05.012 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2013 Aug;32(8):769-76. doi: 
      10.1016/j.healun.2013.05.012.