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Neutrophil FcγRIIA availability is associated with disease activity in systemic lupus erythematosus

Bengtsson, Anders A. LU ; Tyden, Helena LU and Lood, Christian LU (2020) In Arthritis Research and Therapy 22.
Abstract

Background: Immune complexes (ICs) are detectable in a variety of inflammatory diseases, including systemic lupus erythematosus (SLE), reflecting autoantibody binding to antigens. Though ICs are the main contributors to disease pathogenesis through FcγR-mediated inflammation and organ damage, IC levels are not part of the clinical assessment of SLE. The aim of this study was to explore the clinical utility of analyzing levels of ICs in SLE patients using a novel technology, IC-FLOW. Methods: Paired serum samples, at the time point of high and low disease activity (n = 92), were analyzed using two assays: an IC ELISA from a commercial company and a novel in-house flow cytometry-based method, IC-FLOW. IC-FLOW measures FcγRIIA availability... (More)

Background: Immune complexes (ICs) are detectable in a variety of inflammatory diseases, including systemic lupus erythematosus (SLE), reflecting autoantibody binding to antigens. Though ICs are the main contributors to disease pathogenesis through FcγR-mediated inflammation and organ damage, IC levels are not part of the clinical assessment of SLE. The aim of this study was to explore the clinical utility of analyzing levels of ICs in SLE patients using a novel technology, IC-FLOW. Methods: Paired serum samples, at the time point of high and low disease activity (n = 92), were analyzed using two assays: an IC ELISA from a commercial company and a novel in-house flow cytometry-based method, IC-FLOW. IC-FLOW measures FcγRIIA availability on the neutrophil cell surface by flow cytometry, whereas the commercial ELISA measures IC binding to C1q. Results: Using IC-FLOW, 90% of SLE patients with active disease had elevated levels of circulating ICs (p < 0.0001). Using the commercial assay, only 17% of SLE patients had elevated levels of circulating ICs. For both assays, levels of ICs reflected active disease as determined by SLEDAI (r = 0.45, p < 0.0001) and were associated with type I IFN activity (r = 0.37, p = 0.001), and complement consumption (p = 0.0002). Levels of ICs measured with IC-FLOW, but not with the commercial ELISA, were associated with active lupus nephritis (p = 0.004). Conclusions: This novel FcγRIIA-IC assay can detect levels of circulating ICs in patients with SLE. Analyzing IC levels may facilitate monitoring of disease activity, as well as identify patients at risk of lupus nephritis, allowing for early preventive interventions.

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author
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organization
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type
Contribution to journal
publication status
published
subject
keywords
Biomarker, Immune complex, Interferon, Nephritis, Systemic lupus erythematosus
in
Arthritis Research and Therapy
volume
22
article number
126
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85085639240
  • pmid:32471491
ISSN
1478-6354
DOI
10.1186/s13075-020-02221-z
language
English
LU publication?
yes
id
3f7cd45c-1772-4369-bc15-1358aaaa98f1
date added to LUP
2020-06-16 09:00:03
date last changed
2024-07-10 17:44:23
@article{3f7cd45c-1772-4369-bc15-1358aaaa98f1,
  abstract     = {{<p>Background: Immune complexes (ICs) are detectable in a variety of inflammatory diseases, including systemic lupus erythematosus (SLE), reflecting autoantibody binding to antigens. Though ICs are the main contributors to disease pathogenesis through FcγR-mediated inflammation and organ damage, IC levels are not part of the clinical assessment of SLE. The aim of this study was to explore the clinical utility of analyzing levels of ICs in SLE patients using a novel technology, IC-FLOW. Methods: Paired serum samples, at the time point of high and low disease activity (n = 92), were analyzed using two assays: an IC ELISA from a commercial company and a novel in-house flow cytometry-based method, IC-FLOW. IC-FLOW measures FcγRIIA availability on the neutrophil cell surface by flow cytometry, whereas the commercial ELISA measures IC binding to C1q. Results: Using IC-FLOW, 90% of SLE patients with active disease had elevated levels of circulating ICs (p &lt; 0.0001). Using the commercial assay, only 17% of SLE patients had elevated levels of circulating ICs. For both assays, levels of ICs reflected active disease as determined by SLEDAI (r = 0.45, p &lt; 0.0001) and were associated with type I IFN activity (r = 0.37, p = 0.001), and complement consumption (p = 0.0002). Levels of ICs measured with IC-FLOW, but not with the commercial ELISA, were associated with active lupus nephritis (p = 0.004). Conclusions: This novel FcγRIIA-IC assay can detect levels of circulating ICs in patients with SLE. Analyzing IC levels may facilitate monitoring of disease activity, as well as identify patients at risk of lupus nephritis, allowing for early preventive interventions.</p>}},
  author       = {{Bengtsson, Anders A. and Tyden, Helena and Lood, Christian}},
  issn         = {{1478-6354}},
  keywords     = {{Biomarker; Immune complex; Interferon; Nephritis; Systemic lupus erythematosus}},
  language     = {{eng}},
  month        = {{05}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Arthritis Research and Therapy}},
  title        = {{Neutrophil FcγRIIA availability is associated with disease activity in systemic lupus erythematosus}},
  url          = {{http://dx.doi.org/10.1186/s13075-020-02221-z}},
  doi          = {{10.1186/s13075-020-02221-z}},
  volume       = {{22}},
  year         = {{2020}},
}