PMID- 20615726
OWN - NLM
STAT- MEDLINE
DCOM- 20110301
LR  - 20211020
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Print)
IS  - 1053-2498 (Linking)
VI  - 29
IP  - 11
DP  - 2010 Nov
TI  - Characterization of immune responses to cardiac self-antigens myosin and vimentin 
      in human cardiac allograft recipients with antibody-mediated rejection and 
      cardiac allograft vasculopathy.
PG  - 1277-85
LID - 10.1016/j.healun.2010.05.025 [doi]
AB  - BACKGROUND: Herein we study the role of donor-specific antibodies (DSA) to 
      mismatched human leukocyte antigen (HLA) and antibodies (Abs) to the cardiac 
      self-antigens myosin (MYO) and vimentin (VIM) in the pathogenesis of acute 
      antibody-mediated rejection (AMR) in the early post-transplant period (EP, <12 
      months) and cardiac allograft vasculopathy (CAV) in the late post-transplant 
      period (LP, >12 months) after heart transplantation (HTx). METHODS: One hundred 
      forty-eight HTx recipients (65 in EP, 83 in LP) were enrolled in the study. 
      Development of DSA was determined by Luminex. Circulating Abs against MYO and VIM 
      in sera were measured using enzyme-linked immunoassay (ELISA). Frequency of CD4+ 
      T-helper cells (CD4+ Th) secreting interferon (IFN)-gamma, interleukin (IL)-17, IL-10 
      or IL-5 specific to either MYO or VIM were analyzed in vitro using ELISpot 
      assays. RESULTS: AMR patients were more likely DSA positive (AMR-: 15%; AMR+: 
      70%; p = 0.03) and demonstrated increased Abs to MYO (AMR-: 144 +/- 115 mug/ml; 
      AMR+: 285 +/- 70 mug/ml; p = 0.033) and VIM (AMR-: 37 +/- 19 mug/ml; AMR+: 103 +/- 43 
      mug/ml; p = 0.014). AMR patients demonstrated increased IL-5 CD4+ Th cells 
      specific to MYO (5.2 +/- 0.9 fold, p = 0.003) and VIM (7.3 +/- 2.9-fold, p = 0.004) 
      and decreased IL-10 CD4+ Th cells specific to MYO (2.2 +/- 0.4-fold, p = 0.009) and 
      VIM (1.7 +/- 0.2-fold, p = 0.03). CAV patients were more likely DSA positive 
      (CAV-): 25%; CAV+: 79%; p = 0.03) and demonstrated increased Abs to MYO (CAV-: 
      191 +/- 120 mug/ml; CAV+: 550 +/- 98 mug/ml; p = 0.025) and VIM (CAV-: 55 +/- 25 mug/ml; 
      CAV+: 255 +/- 49 mug/ml; p = 0.001). CAV patients demonstrated increased IL-17 CD4+ 
      Th cells specific to MYO (10.5 +/- 7.3-fold, p = 0.002) and VIM (7.0 +/- 3.9-fold, p 
      = 0.003). CONCLUSIONS: The presence of DSA in AMR and CAV is significantly 
      associated with development of Abs to MYO and VIM in post-HTx patients. Induction 
      of high CD4+ Th cells specific to cardiac self-antigens that secrete 
      predominantly IL-5 and IL-17 plays a significant role in the development of Abs 
      to self-antigens leading to AMR and CAV, respectively.
CI  - Copyright (c) 2010 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Nath, Dilip S
AU  - Nath DS
AD  - Division of Cardiothoracic Surgery, Barnes-Jewish Hospital, St. Louis, Missouri, 
      USA.
FAU - Ilias Basha, Haseeb
AU  - Ilias Basha H
FAU - Tiriveedhi, Venkataswarup
AU  - Tiriveedhi V
FAU - Alur, Chiraag
AU  - Alur C
FAU - Phelan, Donna
AU  - Phelan D
FAU - Ewald, Gregory A
AU  - Ewald GA
FAU - Moazami, Nader
AU  - Moazami N
FAU - Mohanakumar, Thalachallour
AU  - Mohanakumar T
LA  - eng
GR  - T32 HL007776/HL/NHLBI NIH HHS/United States
GR  - T32 HL007776-15/HL/NHLBI NIH HHS/United States
GR  - T32 HL07776/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100707
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)
RN  - 0 (Autoantigens)
RN  - 0 (Interleukin-5)
RN  - 0 (Vimentin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.6.4.1 (Myosins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies/*blood
MH  - Autoantigens/*immunology
MH  - Female
MH  - Graft Rejection/*immunology
MH  - Heart Transplantation/*immunology
MH  - Humans
MH  - Interferon-gamma/blood
MH  - Interleukin-5/blood
MH  - Male
MH  - Middle Aged
MH  - Myosins/*immunology
MH  - Prospective Studies
MH  - Retrospective Studies
MH  - Tissue Donors
MH  - Transplantation
MH  - Transplantation, Homologous
MH  - Vascular Diseases/*immunology
MH  - Vimentin/*immunology
PMC - PMC2963681
MID - NIHMS210365
EDAT- 2010/07/10 06:00
MHDA- 2011/03/02 06:00
PMCR- 2011/11/01
CRDT- 2010/07/10 06:00
PHST- 2010/03/29 00:00 [received]
PHST- 2010/05/13 00:00 [revised]
PHST- 2010/05/26 00:00 [accepted]
PHST- 2010/07/10 06:00 [entrez]
PHST- 2010/07/10 06:00 [pubmed]
PHST- 2011/03/02 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - S1053-2498(10)00349-9 [pii]
AID - 10.1016/j.healun.2010.05.025 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2010 Nov;29(11):1277-85. doi: 
      10.1016/j.healun.2010.05.025. Epub 2010 Jul 7.