PMID- 27188505
OWN - NLM
STAT- MEDLINE
DCOM- 20171003
LR  - 20220408
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Linking)
VI  - 90
IP  - 2
DP  - 2016 Aug
TI  - Non-HLA antibodies against endothelial targets bridging allo- and autoimmunity.
PG  - 280-288
LID - S0085-2538(16)30071-0 [pii]
LID - 10.1016/j.kint.2016.03.019 [doi]
AB  - Detrimental actions of donor-specific antibodies (DSAs) directed against both 
      major histocompatibility antigens (human leukocyte antigen [HLA]) and specific 
      non-HLA antigens expressed on the allograft endothelium are a flourishing 
      research area in kidney transplantation. Newly developed solid-phase assays 
      enabling detection of functional non-HLA antibodies targeting G protein-coupled 
      receptors such as angiotensin type I receptor and endothelin type A receptor were 
      instrumental in providing long-awaited confirmation of their broad clinical 
      relevance. Numerous recent clinical studies implicate angiotensin type I receptor 
      and endothelin type A receptor antibodies as prognostic biomarkers for earlier 
      occurrence and severity of acute and chronic immunologic complications in solid 
      organ transplantation, stem cell transplantation, and systemic autoimmune 
      vascular disease. Angiotensin type 1 receptor and endothelin type A receptor 
      antibodies exert their pathophysiologic effects alone and in synergy with 
      HLA-DSA. Recently identified antiperlecan antibodies are also implicated in 
      accelerated allograft vascular pathology. In parallel, protein array technology 
      platforms enabled recognition of new endothelial surface antigens implicated in 
      endothelial cell activation. Upon target antigen recognition, non-HLA antibodies 
      act as powerful inducers of phenotypic perturbations in endothelial cells via 
      activation of distinct intracellular cell-signaling cascades. Comprehensive 
      diagnostic assessment strategies focusing on both HLA-DSA and non-HLA antibody 
      responses could substantially improve immunologic risk stratification before 
      transplantation, help to better define subphenotypes of antibody-mediated 
      rejection, and lead to timely initiation of targeted therapies. Better 
      understanding of similarities and dissimilarities in HLA-DSA and distinct non-HLA 
      antibody-related mechanisms of endothelial damage should facilitate discovery of 
      common downstream signaling targets and pave the way for the development of 
      endothelium-centered therapeutic strategies to accompany intensified 
      immunosuppression and/or mechanical removal of antibodies.
CI  - Copyright (c) 2016 International Society of Nephrology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Dragun, Duska
AU  - Dragun D
AD  - Clinic for Nephrology and Critical Care Medicine, Campus Virchow-Klinikum and 
      Center for Cardiovascular Research, Medical Faculty of the Charite Berlin, 
      Berlin, Germany; Berlin Institute of Health, Berlin, Germany. Electronic address: 
      duska.dragun@charite.de.
FAU - Catar, Rusan
AU  - Catar R
AD  - Clinic for Nephrology and Critical Care Medicine, Campus Virchow-Klinikum and 
      Center for Cardiovascular Research, Medical Faculty of the Charite Berlin, 
      Berlin, Germany; Berlin Institute of Health, Berlin, Germany.
FAU - Philippe, Aurelie
AU  - Philippe A
AD  - Clinic for Nephrology and Critical Care Medicine, Campus Virchow-Klinikum and 
      Center for Cardiovascular Research, Medical Faculty of the Charite Berlin, 
      Berlin, Germany.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160514
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Autoantibodies)
RN  - 0 (Endothelin A Receptor Antagonists)
RN  - 0 (HLA Antigens)
RN  - 0 (Heparan Sulfate Proteoglycans)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Endothelin A)
RN  - 143972-95-6 (perlecan)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/therapeutic use
MH  - Autoantibodies/*immunology
MH  - Autoimmunity/*immunology
MH  - Endothelial Cells/*immunology/metabolism
MH  - Endothelin A Receptor Antagonists/therapeutic use
MH  - Graft Rejection/*immunology/therapy
MH  - Graft Survival/immunology
MH  - HLA Antigens/immunology
MH  - Heparan Sulfate Proteoglycans/immunology
MH  - Humans
MH  - Immune Tolerance/immunology
MH  - Immunity, Humoral/*immunology
MH  - Immunosuppressive Agents/therapeutic use
MH  - Kidney Transplantation/*adverse effects
MH  - Plasmapheresis
MH  - Receptor, Angiotensin, Type 1/immunology
MH  - Receptor, Endothelin A/immunology
MH  - Transplantation, Homologous/adverse effects
OTO - NOTNLM
OT  - acute rejection
OT  - angiotensin
OT  - endothelium
OT  - renin angiotensin system
OT  - signaling
EDAT- 2016/05/18 06:00
MHDA- 2017/10/04 06:00
CRDT- 2016/05/19 06:00
PHST- 2016/01/06 00:00 [received]
PHST- 2016/03/12 00:00 [revised]
PHST- 2016/03/17 00:00 [accepted]
PHST- 2016/05/19 06:00 [entrez]
PHST- 2016/05/18 06:00 [pubmed]
PHST- 2017/10/04 06:00 [medline]
AID - S0085-2538(16)30071-0 [pii]
AID - 10.1016/j.kint.2016.03.019 [doi]
PST - ppublish
SO  - Kidney Int. 2016 Aug;90(2):280-288. doi: 10.1016/j.kint.2016.03.019. Epub 2016 
      May 14.