Neutrophil Extracellular Traps That Are Not Degraded in Systemic Lupus Erythematosus Activate Complement Exacerbating the Disease.
Leffler, Jonatan LU ; Martin, Myriam LU ; Gullstrand, Birgitta LU ; Tydén, Helena LU ; Lood, Christian LU ; Truedsson, Lennart LU ; Bengtsson, Anders LU and Blom, Anna LU
(2012)
In Journal of immunology
188(7).
p.3522-3531
- Abstract
- Ongoing inflammation including activation of the complement system is a hallmark of systemic lupus erythematosus (SLE). Antimicrobial neutrophil extracellular traps (NETs) are composed of secreted chromatin that may act as a source of autoantigens typical for SLE. In this study, we investigated how complement interacts with NETs and how NET degradation is affected by complement in SLE patients. We found that sera from a subset of patients with active SLE had a reduced ability to degrade in vitro-generated NETs, which was mostly restored when these patients were in remission. Patients that failed to degrade NETs had a more active disease and they also displayed lower levels of complement proteins C4 and C3 in blood. We discovered that NETs... (More)
- Ongoing inflammation including activation of the complement system is a hallmark of systemic lupus erythematosus (SLE). Antimicrobial neutrophil extracellular traps (NETs) are composed of secreted chromatin that may act as a source of autoantigens typical for SLE. In this study, we investigated how complement interacts with NETs and how NET degradation is affected by complement in SLE patients. We found that sera from a subset of patients with active SLE had a reduced ability to degrade in vitro-generated NETs, which was mostly restored when these patients were in remission. Patients that failed to degrade NETs had a more active disease and they also displayed lower levels of complement proteins C4 and C3 in blood. We discovered that NETs activated complement in vitro and that deposited C1q inhibited NET degradation including a direct inhibition of DNase-I by C1q. Complement deposition on NETs may facilitate autoantibody production, and indeed, Abs against NETs and NET epitopes were more pronounced in patients with impaired ability to degrade NETs. NET-bound autoantibodies inhibited degradation but also further increased C1q deposition, potentially exacerbating the disease. Thus, NETs are a potent complement activator, and this interaction may play an important role in SLE. Targeting complement with inhibitors or by removing complement activators such as NETs could be beneficial for patients with SLE. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2366707
- author
- Leffler, Jonatan
LU
; Martin, Myriam
LU
; Gullstrand, Birgitta
LU
; Tydén, Helena
LU
; Lood, Christian
LU
; Truedsson, Lennart
LU
; Bengtsson, Anders
LU
and Blom, Anna
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of immunology
- volume
- 188
- issue
- 7
- pages
- 3522 - 3531
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000302150300066
- pmid:22345666
- scopus:84859375702
- pmid:22345666
- ISSN
- 1550-6606
- DOI
- 10.4049/jimmunol.1102404
- language
- English
- LU publication?
- yes
- id
- 844e6d15-c2fe-4f04-b3c2-2d9e5fd7ef42 (old id 2366707)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22345666?dopt=Abstract
- date added to LUP
- 2016-04-04 09:40:29
- date last changed
- 2022-05-17 01:25:00
@article{844e6d15-c2fe-4f04-b3c2-2d9e5fd7ef42,
abstract = {{Ongoing inflammation including activation of the complement system is a hallmark of systemic lupus erythematosus (SLE). Antimicrobial neutrophil extracellular traps (NETs) are composed of secreted chromatin that may act as a source of autoantigens typical for SLE. In this study, we investigated how complement interacts with NETs and how NET degradation is affected by complement in SLE patients. We found that sera from a subset of patients with active SLE had a reduced ability to degrade in vitro-generated NETs, which was mostly restored when these patients were in remission. Patients that failed to degrade NETs had a more active disease and they also displayed lower levels of complement proteins C4 and C3 in blood. We discovered that NETs activated complement in vitro and that deposited C1q inhibited NET degradation including a direct inhibition of DNase-I by C1q. Complement deposition on NETs may facilitate autoantibody production, and indeed, Abs against NETs and NET epitopes were more pronounced in patients with impaired ability to degrade NETs. NET-bound autoantibodies inhibited degradation but also further increased C1q deposition, potentially exacerbating the disease. Thus, NETs are a potent complement activator, and this interaction may play an important role in SLE. Targeting complement with inhibitors or by removing complement activators such as NETs could be beneficial for patients with SLE.}},
author = {{Leffler, Jonatan and Martin, Myriam and Gullstrand, Birgitta and Tydén, Helena and Lood, Christian and Truedsson, Lennart and Bengtsson, Anders and Blom, Anna}},
issn = {{1550-6606}},
language = {{eng}},
number = {{7}},
pages = {{3522--3531}},
publisher = {{American Association of Immunologists}},
series = {{Journal of immunology}},
title = {{Neutrophil Extracellular Traps That Are Not Degraded in Systemic Lupus Erythematosus Activate Complement Exacerbating the Disease.}},
url = {{http://dx.doi.org/10.4049/jimmunol.1102404}},
doi = {{10.4049/jimmunol.1102404}},
volume = {{188}},
year = {{2012}},
}