PMID- 22189942
OWN - NLM
STAT- MEDLINE
DCOM- 20120522
LR  - 20220310
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 302
IP  - 7
DP  - 2012 Apr 1
TI  - Antibodies to kidney endothelial cells contribute to a "leaky" glomerular barrier 
      in patients with chronic kidney diseases.
PG  - F884-94
LID - 10.1152/ajprenal.00250.2011 [doi]
AB  - Anti-endothelial cell antibodies (AECA) have been reported to cause endothelial 
      dysfunction, but their clinical importance for tissue-specific endothelial cells 
      is not clear. We hypothesized that AECA reactive with human kidney endothelial 
      cells (HKEC) may cause renal endothelial dysfunction in patients with chronic 
      kidney diseases. We report that a higher fraction (56%) of end-stage renal 
      disease (ESRD) patients than healthy controls (5%) have AECA reactive against 
      kidney endothelial cells (P <0.001). The presence of antibodies was associated 
      with female gender (P < 0.001), systolic hypertension (P < 0.01), and elevated 
      TNF-alpha (P < 0.05). These antibodies markedly decrease expression of both adherens 
      and tight junction proteins VE-cadherin, claudin-1, and zonula occludens-1 and 
      provoked a rapid increase in cytosolic free Ca(2+) and rearrangement of actin 
      filaments in HKEC compared with controls. This was followed by an enhancement in 
      protein flux and phosphorylation of VE-cadherin, events associated with augmented 
      endothelial cell permeability. Additionally, kidney biopsies from ESRD patients 
      with AECA but not controls demonstrated a marked decrease in adherens and tight 
      junctions in glomerular endothelium, confirming our in vitro data. In summary, 
      our data demonstrate a causal link between AECA and their capacity to induce 
      alterations in glomerular vascular permeability.
FAU - Hernandez, Nidia Maritza
AU  - Hernandez NM
AD  - Dept. of Transplantation Surgery, Laboratory for Transplantation and Regenerative 
      Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska Science 
      Park, Medicinaregatan 8A, Gothenburg, Sweden.
FAU - Casselbrant, Anna
AU  - Casselbrant A
FAU - Joshi, Meghnad
AU  - Joshi M
FAU - Johansson, Bengt R
AU  - Johansson BR
FAU - Sumitran-Holgersson, Suchitra
AU  - Sumitran-Holgersson S
LA  - eng
GR  - Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111221
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Actins)
RN  - 0 (Antigens, CD)
RN  - 0 (Autoantibodies)
RN  - 0 (CLDN1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Claudin-1)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Membrane Proteins)
RN  - 0 (anti-endothelial cell antibody)
RN  - 0 (cadherin 5)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Actins/metabolism
MH  - Adherens Junctions/*physiology
MH  - Adult
MH  - Antigens, CD/metabolism
MH  - Autoantibodies/*physiology
MH  - Cadherins/metabolism
MH  - Calcium/metabolism
MH  - Case-Control Studies
MH  - Claudin-1
MH  - Cytosol/metabolism
MH  - Female
MH  - Glomerular Filtration Barrier/*metabolism
MH  - Humans
MH  - Immunoglobulin G/blood
MH  - Kidney Failure, Chronic/*immunology/metabolism
MH  - Male
MH  - Membrane Proteins/metabolism
MH  - Middle Aged
MH  - Phosphorylation
MH  - Pilot Projects
MH  - Tight Junctions/*physiology
EDAT- 2011/12/23 06:00
MHDA- 2012/05/23 06:00
CRDT- 2011/12/23 06:00
PHST- 2011/12/23 06:00 [entrez]
PHST- 2011/12/23 06:00 [pubmed]
PHST- 2012/05/23 06:00 [medline]
AID - ajprenal.00250.2011 [pii]
AID - 10.1152/ajprenal.00250.2011 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2012 Apr 1;302(7):F884-94. doi: 
      10.1152/ajprenal.00250.2011. Epub 2011 Dec 21.