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Activation of complement by pigment epithelium-derived factor in rheumatoid arthritis

Vogt, Leonie M. LU ; Talens, Simone LU ; Kwasniewicz, Ewa LU ; Scavenius, Carsten; Struglics, André LU ; Enghild, Jan J; Saxne, Tore LU and Blom, Anna M. LU (2017) In Journal of Immunology 199(3). p.1113-1121
Abstract

The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas... (More)

The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d-PEDF complexes found in sera arise from the joints, as well as from other tissues, and levels of the complexes did not differ in sera of RA patients and healthy controls. When immobilized, recombinant PEDF expressed in eukaryotic cells activated the classical complement pathway but not the alternative or lectin pathways. C1q protein was demonstrated to bind immobilized PEDF, and PEDF was shown to bind to immobilized C1q, in particular its head regions, which are known to interact with other activators of the classical pathway. Our results call for further investigation into the role of PEDF in inflammatory processes in the joint, which, in combination with classical complement activation, appears to be part of a (patho-)physiologic response.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
199
issue
3
pages
9 pages
publisher
American Association of Immunologists
external identifiers
  • scopus:85026255678
  • wos:000406182600030
ISSN
0022-1767
DOI
10.4049/jimmunol.1700018
language
English
LU publication?
yes
id
5a679dec-ac08-451b-9163-a5ceb3885fb9
date added to LUP
2017-08-04 10:18:31
date last changed
2017-09-18 11:40:55
@article{5a679dec-ac08-451b-9163-a5ceb3885fb9,
  abstract     = {<p>The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d-PEDF complexes found in sera arise from the joints, as well as from other tissues, and levels of the complexes did not differ in sera of RA patients and healthy controls. When immobilized, recombinant PEDF expressed in eukaryotic cells activated the classical complement pathway but not the alternative or lectin pathways. C1q protein was demonstrated to bind immobilized PEDF, and PEDF was shown to bind to immobilized C1q, in particular its head regions, which are known to interact with other activators of the classical pathway. Our results call for further investigation into the role of PEDF in inflammatory processes in the joint, which, in combination with classical complement activation, appears to be part of a (patho-)physiologic response.</p>},
  author       = {Vogt, Leonie M. and Talens, Simone and Kwasniewicz, Ewa and Scavenius, Carsten and Struglics, André and Enghild, Jan J and Saxne, Tore and Blom, Anna M.},
  issn         = {0022-1767},
  language     = {eng},
  month        = {08},
  number       = {3},
  pages        = {1113--1121},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Activation of complement by pigment epithelium-derived factor in rheumatoid arthritis},
  url          = {http://dx.doi.org/10.4049/jimmunol.1700018},
  volume       = {199},
  year         = {2017},
}