PMID- 28988608
OWN - NLM
STAT- MEDLINE
DCOM- 20180716
LR  - 20180716
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 36
IP  - 12
DP  - 2017 Dec
TI  - Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes.
PG  - 1329-1335
LID - S1053-2498(17)31989-7 [pii]
LID - 10.1016/j.healun.2017.09.004 [doi]
AB  - BACKGROUND: In the past decade, C4d has emerged as a potential marker for 
      antibody-mediated rejection (AMR); however, evidence on its use as a prognostic 
      tool has been controversial. Although the International Society for Heart and 
      Lung Transplantation guideline recommends early routine surveillance of C4d in 
      heart transplantation, there is no consensus on its value in the pathologic 
      assessment of AMR. Herein we present a correlation analysis of C4d 
      immunoreactivity in endomyocardial biopsies with clinical cardiac dysfunction, 
      cellular rejection, human leukocyte antigen (HLA) status, cardiac allograft 
      vasculopathy (CAV) and death. METHODS: A total of 5,840 endomyocardial biopsies 
      from 296 heart transplant recipients (January 2004 to December 2014) were stained 
      prospectively for C4d. Strong, diffuse endothelial staining was considered 
      positive. All patients had at least 1 year of follow-up. Positive C4d staining 
      was present in 53 biopsies from 28 patients. Sixteen of 28 patients had 
      clinically significant cardiac dysfunction at the time of positive biopsy. In 
      C4d-positive patients, the mean panel-reactive antibody (PRA) level was 33%. Ten 
      patients demonstrated a first C4d positivity within the first year 
      post-transplant, whereas 18 patients had C4d positivity after 1 year 
      post-transplant. At autopsy, all 11 C4d-positive patients examined demonstrated 
      cardiac allograft vasculopathy (CAV) as the underlying cause of death. In 
      contrast, only 2 of 8 (25%) C4d-negative patients had CAV at autopsy. In the 
      surviving cohort, there was an angiographic diagnosis of higher-than-moderate CAV 
      in 10 patients (3.8%). RESULTS: C4d-positive patients contributed to 67% of the 
      overall institutional mortality in heart transplant recipients. Late C4d 
      positivity (>1 year post-transplant) demonstrated an even higher risk for 
      developing CAV and poor prognosis than early C4d positivity (within 1 year). In 
      the C4d-negative group with postmortem examination, 75% (6 of 8) deaths were due 
      to non-cardiac causes. CONCLUSIONS: Our findings show a positive association of 
      C4d with CAV and death. We identified a prognostic role for C4d in heart 
      transplantation warranting routine long-term detection of this marker in the 
      pathologic evaluation of cardiac AMR.
CI  - Copyright (c) 2017 International Society for the Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Husain, Aliya N
AU  - Husain AN
AD  - Department of Pathology, The University of Chicago Medicine, Chicago, Illinois, 
      USA. Electronic address: aliya.husain@uchospitals.edu.
FAU - Mirza, Kamran M
AU  - Mirza KM
AD  - Department of Pathology, The University of Chicago Medicine, Chicago, Illinois, 
      USA.
FAU - Fedson, Savitri E
AU  - Fedson SE
AD  - Department of Medicine, The University of Chicago Medicine, Chicago, Illinois, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20170914
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  - 80295-50-7 (Complement C4b)
SB  - IM
MH  - Adult
MH  - Allografts
MH  - Biopsy
MH  - Complement C4b/immunology/*metabolism
MH  - Female
MH  - Follow-Up Studies
MH  - *Forecasting
MH  - Graft Rejection/immunology/*metabolism/pathology
MH  - *Heart Transplantation
MH  - Humans
MH  - Immunohistochemistry/*methods
MH  - Male
MH  - Middle Aged
MH  - Myocardium/*metabolism/pathology
MH  - Prognosis
MH  - Retrospective Studies
OTO - NOTNLM
OT  - C4d
OT  - antibody-mediated rejection
OT  - cardiac allograft
OT  - cardiac allograft vasculopathy
OT  - endomyocardial biopsy
OT  - immunohistochemistry
EDAT- 2017/10/11 06:00
MHDA- 2018/07/17 06:00
CRDT- 2017/10/10 06:00
PHST- 2016/11/23 00:00 [received]
PHST- 2017/08/30 00:00 [revised]
PHST- 2017/09/11 00:00 [accepted]
PHST- 2017/10/11 06:00 [pubmed]
PHST- 2018/07/17 06:00 [medline]
PHST- 2017/10/10 06:00 [entrez]
AID - S1053-2498(17)31989-7 [pii]
AID - 10.1016/j.healun.2017.09.004 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2017 Dec;36(12):1329-1335. doi: 
      10.1016/j.healun.2017.09.004. Epub 2017 Sep 14.