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Analyses of plasma inflammatory proteins reveal biomarkers predictive of subsequent development of giant cell arteritis : a prospective study

Wadström, Karin LU ; Jacobsson, Lennart T H LU ; Mohammad, Aladdin J LU ; Warrington, Kenneth J ; Matteson, Eric L ; Jakobsson, Magnus E LU and Turesson, Carl LU (2023) In Rheumatology (Oxford, England) 62(6). p.2304-2311
Abstract

OBJECTIVE: To investigate the relation between biomarkers of inflammation and subsequent development of giant cell arteritis (GCA).

METHOD: Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30447), established 1991-1996, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth, and year of screening were selected from the study cohort. Baseline plasma samples were analyzed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the... (More)

OBJECTIVE: To investigate the relation between biomarkers of inflammation and subsequent development of giant cell arteritis (GCA).

METHOD: Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30447), established 1991-1996, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth, and year of screening were selected from the study cohort. Baseline plasma samples were analyzed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on Eigenvalues, proteins with a factor loading of > 0.50 were investigated.

RESULTS: 94 cases with a confirmed incident diagnosis of GCA (median 11.9 years after inclusion) were identified. Among biomarkers with a priori hypotheses, IFN-γ was positively associated with GCA (odds ratio (OR) per SD 1.52; 95% CI 1.00-2.30). Eight biomarkers in the hypothesis-generating analyses were significantly associated with development of GCA. Among these, higher levels of IFN-γ (OR 2.37; 95% CI 1.14-4.92) and MCP3 (OR 4.27; 95% CI 1.26-14.53) were particularly associated with increased risk of GCA in the subset sampled <8.5 years before diagnosis. Several other proteins known to be important for T cell function were also associated with GCA in these analyses, e.g. CXCL9, IL-2, CD40 and CCL25.

CONCLUSION: Elevated IFN-γ levels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Rheumatology (Oxford, England)
volume
62
issue
6
pages
2304 - 2311
publisher
Oxford University Press
external identifiers
  • scopus:85143072450
  • pmid:36255228
ISSN
1462-0332
DOI
10.1093/rheumatology/keac581
project
Pain in early rheumatoid arthritis - predictors and development over time
language
English
LU publication?
yes
additional info
© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
id
1ab8eaf8-8849-4e30-9cbb-86dd4020d93f
date added to LUP
2022-10-20 15:41:38
date last changed
2024-06-15 01:04:02
@article{1ab8eaf8-8849-4e30-9cbb-86dd4020d93f,
  abstract     = {{<p>OBJECTIVE: To investigate the relation between biomarkers of inflammation and subsequent development of giant cell arteritis (GCA).</p><p>METHOD: Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30447), established 1991-1996, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth, and year of screening were selected from the study cohort. Baseline plasma samples were analyzed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on Eigenvalues, proteins with a factor loading of &gt; 0.50 were investigated.</p><p>RESULTS: 94 cases with a confirmed incident diagnosis of GCA (median 11.9 years after inclusion) were identified. Among biomarkers with a priori hypotheses, IFN-γ was positively associated with GCA (odds ratio (OR) per SD 1.52; 95% CI 1.00-2.30). Eight biomarkers in the hypothesis-generating analyses were significantly associated with development of GCA. Among these, higher levels of IFN-γ (OR 2.37; 95% CI 1.14-4.92) and MCP3 (OR 4.27; 95% CI 1.26-14.53) were particularly associated with increased risk of GCA in the subset sampled &lt;8.5 years before diagnosis. Several other proteins known to be important for T cell function were also associated with GCA in these analyses, e.g. CXCL9, IL-2, CD40 and CCL25.</p><p>CONCLUSION: Elevated IFN-γ levels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.</p>}},
  author       = {{Wadström, Karin and Jacobsson, Lennart T H and Mohammad, Aladdin J and Warrington, Kenneth J and Matteson, Eric L and Jakobsson, Magnus E and Turesson, Carl}},
  issn         = {{1462-0332}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{2304--2311}},
  publisher    = {{Oxford University Press}},
  series       = {{Rheumatology (Oxford, England)}},
  title        = {{Analyses of plasma inflammatory proteins reveal biomarkers predictive of subsequent development of giant cell arteritis : a prospective study}},
  url          = {{http://dx.doi.org/10.1093/rheumatology/keac581}},
  doi          = {{10.1093/rheumatology/keac581}},
  volume       = {{62}},
  year         = {{2023}},
}