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Complement Activation Associated with ADAMTS13 Deficiency in Human and Murine Thrombotic Microangiopathy.

Tati, Ramesh LU ; Kristoffersson, Ann-Charlotte LU ; Ståhl, Anne-lie LU ; Rebetz, Johan LU orcid ; Wang, Li ; Licht, Christoph ; Motto, David and Karpman, Diana LU orcid (2013) In Journal of Immunology 191(5). p.2184-2193
Abstract
This study addressed the contribution of ADAMTS13 deficiency to complement activation in thrombotic thrombocytopenic purpura (TTP). Renal tissue and blood samples were available from 12 TTP patients. C3 and C5b-9 deposition were demonstrated in the renal cortex of two TTP patients, by immunofluorescence and immunohistochemistry, respectively. C3 was also demonstrated in the glomeruli of Shiga toxin-2-treated Adamts13(-/-) mice (n = 6 of 7), but less in mice that were not Shiga toxin-2 treated (n = 1 of 8, p < 0.05) or wild-type mice (n = 0 of 7). TTP patient plasma (n = 9) contained significantly higher levels of complement-coated endothelial microparticles than control plasma (n = 13), as detected by flow cytometry. Exposure of... (More)
This study addressed the contribution of ADAMTS13 deficiency to complement activation in thrombotic thrombocytopenic purpura (TTP). Renal tissue and blood samples were available from 12 TTP patients. C3 and C5b-9 deposition were demonstrated in the renal cortex of two TTP patients, by immunofluorescence and immunohistochemistry, respectively. C3 was also demonstrated in the glomeruli of Shiga toxin-2-treated Adamts13(-/-) mice (n = 6 of 7), but less in mice that were not Shiga toxin-2 treated (n = 1 of 8, p < 0.05) or wild-type mice (n = 0 of 7). TTP patient plasma (n = 9) contained significantly higher levels of complement-coated endothelial microparticles than control plasma (n = 13), as detected by flow cytometry. Exposure of histamine-stimulated primary glomerular endothelial cells to platelet-rich plasma from patients, or patient platelet-poor plasma combined with normal platelets, in a perfusion system, under shear, induced C3 deposition on von Willebrand factor-platelet strings (on both von Willebrand factor and platelets) and on endothelial cells. Complement activation occurred via the alternative pathway. No C3 was detected when cells were exposed to TTP plasma that was preincubated with EDTA or heat-inactivated, or to control plasma. In the perfusion system, patient plasma induced more release of C3- and C9-coated endothelial microparticles compared with control plasma. The results indicate that the microvascular process induced by ADAMTS13 deficiency triggers complement activation on platelets and the endothelium, which may contribute to formation of thrombotic microangiopathy. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
191
issue
5
pages
2184 - 2193
publisher
American Association of Immunologists
external identifiers
  • wos:000323393300019
  • pmid:23878316
  • scopus:84883420511
  • pmid:23878316
ISSN
1550-6606
DOI
10.4049/jimmunol.1301221
language
English
LU publication?
yes
id
f5012c50-c9c6-4335-9c9c-dcfd37c091e5 (old id 3955663)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23878316?dopt=Abstract
date added to LUP
2016-04-01 10:52:29
date last changed
2022-04-12 18:29:40
@article{f5012c50-c9c6-4335-9c9c-dcfd37c091e5,
  abstract     = {{This study addressed the contribution of ADAMTS13 deficiency to complement activation in thrombotic thrombocytopenic purpura (TTP). Renal tissue and blood samples were available from 12 TTP patients. C3 and C5b-9 deposition were demonstrated in the renal cortex of two TTP patients, by immunofluorescence and immunohistochemistry, respectively. C3 was also demonstrated in the glomeruli of Shiga toxin-2-treated Adamts13(-/-) mice (n = 6 of 7), but less in mice that were not Shiga toxin-2 treated (n = 1 of 8, p &lt; 0.05) or wild-type mice (n = 0 of 7). TTP patient plasma (n = 9) contained significantly higher levels of complement-coated endothelial microparticles than control plasma (n = 13), as detected by flow cytometry. Exposure of histamine-stimulated primary glomerular endothelial cells to platelet-rich plasma from patients, or patient platelet-poor plasma combined with normal platelets, in a perfusion system, under shear, induced C3 deposition on von Willebrand factor-platelet strings (on both von Willebrand factor and platelets) and on endothelial cells. Complement activation occurred via the alternative pathway. No C3 was detected when cells were exposed to TTP plasma that was preincubated with EDTA or heat-inactivated, or to control plasma. In the perfusion system, patient plasma induced more release of C3- and C9-coated endothelial microparticles compared with control plasma. The results indicate that the microvascular process induced by ADAMTS13 deficiency triggers complement activation on platelets and the endothelium, which may contribute to formation of thrombotic microangiopathy.}},
  author       = {{Tati, Ramesh and Kristoffersson, Ann-Charlotte and Ståhl, Anne-lie and Rebetz, Johan and Wang, Li and Licht, Christoph and Motto, David and Karpman, Diana}},
  issn         = {{1550-6606}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{2184--2193}},
  publisher    = {{American Association of Immunologists}},
  series       = {{Journal of Immunology}},
  title        = {{Complement Activation Associated with ADAMTS13 Deficiency in Human and Murine Thrombotic Microangiopathy.}},
  url          = {{http://dx.doi.org/10.4049/jimmunol.1301221}},
  doi          = {{10.4049/jimmunol.1301221}},
  volume       = {{191}},
  year         = {{2013}},
}