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Combination of Autoantibodies Against Different Histone Proteins Influences Complement-dependent Phagocytosis of Necrotic Cell Material by Polymorphonuclear Leukocytes in Systemic Lupus Erythematosus.

Gullstrand, Birgitta LU ; Lefort, Malin H; Tydén, Helena LU ; Jönsen, Andreas LU ; Lood, Christian LU ; Johansson, Åsa LU ; Jacobsen, Søren; Truedsson, Lennart LU and Bengtsson, Anders LU (2012) In Journal of Rheumatology 39(8). p.1619-1627
Abstract
OBJECTIVE:

Polymorphonuclear leukocytes (PMN) with autoantibody-coated engulfed necrotic cell material (NC) are frequently seen in systemic lupus erythematosus (SLE). We evaluated the roles of complement, different antihistone antibodies (anti-H ab), and oxidative burst in the phagocytosis of NC by PMN, as well as association to disease activity and clinical phenotype in SLE.



METHODS:

ELISA and immunoblot were used to measure antibodies to different histone proteins in sera from patients with SLE and complement-deficient individuals. Phagocytosis of NC by PMN and oxidative burst activity was assessed by flow cytometry.



RESULTS:

A clearly increased phagocytosis of NC was... (More)
OBJECTIVE:

Polymorphonuclear leukocytes (PMN) with autoantibody-coated engulfed necrotic cell material (NC) are frequently seen in systemic lupus erythematosus (SLE). We evaluated the roles of complement, different antihistone antibodies (anti-H ab), and oxidative burst in the phagocytosis of NC by PMN, as well as association to disease activity and clinical phenotype in SLE.



METHODS:

ELISA and immunoblot were used to measure antibodies to different histone proteins in sera from patients with SLE and complement-deficient individuals. Phagocytosis of NC by PMN and oxidative burst activity was assessed by flow cytometry.



RESULTS:

A clearly increased phagocytosis of NC was seen in patients with active SLE, which was associated with high levels of anti-H ab concentrations and oxidative burst activity. The complement system contributed to efficient phagocytosis of NC by PMN through activation of the classical pathway, and the phagocytosis was mediated by FcγRIIA, FcγRIIIB, and CR1 in combination. A pattern of high phagocytosis, consumption of classical pathway components, and a broad anti-H ab repertoire was seen particularly in patients with nephritis and serositis. The combination of antibodies to several different histone proteins, often with anti-DNA antibodies, promoted an efficient uptake of NC, whereas antibodies against only histone H1 or a few histones seemed to be of less importance.



CONCLUSION:

The distributions of specificities among anti-H ab are of great importance in the complement-dependent phagocytosis of debris from NC in SLE. Measurement of anti-H ab could be useful in monitoring of this disease and contribute to improved understanding of the autoimmune process. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Rheumatology
volume
39
issue
8
pages
1619 - 1627
publisher
J Rheumatol Publ Co
external identifiers
  • wos:000307795800016
  • pmid:22753651
  • scopus:84864561878
ISSN
0315-162X
DOI
10.3899/jrheum.111511
language
English
LU publication?
yes
id
f8d619b4-3491-4f0d-9c56-500e93fda82f (old id 2967567)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22753651?dopt=Abstract
date added to LUP
2012-08-09 16:13:59
date last changed
2017-07-23 04:53:20
@article{f8d619b4-3491-4f0d-9c56-500e93fda82f,
  abstract     = {OBJECTIVE: <br/><br>
Polymorphonuclear leukocytes (PMN) with autoantibody-coated engulfed necrotic cell material (NC) are frequently seen in systemic lupus erythematosus (SLE). We evaluated the roles of complement, different antihistone antibodies (anti-H ab), and oxidative burst in the phagocytosis of NC by PMN, as well as association to disease activity and clinical phenotype in SLE. <br/><br>
<br/><br>
METHODS: <br/><br>
ELISA and immunoblot were used to measure antibodies to different histone proteins in sera from patients with SLE and complement-deficient individuals. Phagocytosis of NC by PMN and oxidative burst activity was assessed by flow cytometry. <br/><br>
<br/><br>
RESULTS: <br/><br>
A clearly increased phagocytosis of NC was seen in patients with active SLE, which was associated with high levels of anti-H ab concentrations and oxidative burst activity. The complement system contributed to efficient phagocytosis of NC by PMN through activation of the classical pathway, and the phagocytosis was mediated by FcγRIIA, FcγRIIIB, and CR1 in combination. A pattern of high phagocytosis, consumption of classical pathway components, and a broad anti-H ab repertoire was seen particularly in patients with nephritis and serositis. The combination of antibodies to several different histone proteins, often with anti-DNA antibodies, promoted an efficient uptake of NC, whereas antibodies against only histone H1 or a few histones seemed to be of less importance. <br/><br>
<br/><br>
CONCLUSION: <br/><br>
The distributions of specificities among anti-H ab are of great importance in the complement-dependent phagocytosis of debris from NC in SLE. Measurement of anti-H ab could be useful in monitoring of this disease and contribute to improved understanding of the autoimmune process.},
  author       = {Gullstrand, Birgitta and Lefort, Malin H and Tydén, Helena and Jönsen, Andreas and Lood, Christian and Johansson, Åsa and Jacobsen, Søren and Truedsson, Lennart and Bengtsson, Anders},
  issn         = {0315-162X},
  language     = {eng},
  number       = {8},
  pages        = {1619--1627},
  publisher    = {J Rheumatol Publ Co},
  series       = {Journal of Rheumatology},
  title        = {Combination of Autoantibodies Against Different Histone Proteins Influences Complement-dependent Phagocytosis of Necrotic Cell Material by Polymorphonuclear Leukocytes in Systemic Lupus Erythematosus.},
  url          = {http://dx.doi.org/10.3899/jrheum.111511},
  volume       = {39},
  year         = {2012},
}