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.
(Less)
- author
- 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
- organization
- publishing date
- 2017-08-01
- 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
- pmid:28637898
- 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
- 2024-02-29 19:30:43
@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}},
doi = {{10.4049/jimmunol.1700018}},
volume = {{199}},
year = {{2017}},
}