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Comparison of Surrogate Markers of the Type I Interferon Response and Their Ability to Mirror Disease Activity in Systemic Lupus Erythematosus

Enocsson, Helena ; Wetterö, Jonas ; Eloranta, Maija Leena ; Gullstrand, Birgitta LU ; Svanberg, Cecilia ; Larsson, Marie ; Bengtsson, Anders A. LU ; Rönnblom, Lars and Sjöwall, Christopher (2021) In Frontiers in Immunology 12.
Abstract

Objectives: Type I interferons (IFNs) are central and reflective of disease activity in systemic lupus erythematosus (SLE). However, IFN-α levels are notoriously difficult to measure and the type I IFN gene signature (IGS) is not yet available in clinical routine. This study evaluates galectin-9 and an array of chemokines/cytokines in their potential as surrogate markers of type I IFN and/or SLE disease activity. Methods: Healthy controls and well-characterized Swedish SLE patients from two cross-sectional cohorts (n=181; n=59) were included, and a subgroup (n=21) was longitudinally followed. Chemokine/cytokine responses in immune complex triggered IFN-α activity was studied in healthy donor peripheral blood mononuclear cells (PBMC).... (More)

Objectives: Type I interferons (IFNs) are central and reflective of disease activity in systemic lupus erythematosus (SLE). However, IFN-α levels are notoriously difficult to measure and the type I IFN gene signature (IGS) is not yet available in clinical routine. This study evaluates galectin-9 and an array of chemokines/cytokines in their potential as surrogate markers of type I IFN and/or SLE disease activity. Methods: Healthy controls and well-characterized Swedish SLE patients from two cross-sectional cohorts (n=181; n=59) were included, and a subgroup (n=21) was longitudinally followed. Chemokine/cytokine responses in immune complex triggered IFN-α activity was studied in healthy donor peripheral blood mononuclear cells (PBMC). Levels of chemokines/cytokines and galectin-9 were measured by immunoassays. Gene expression was quantified by qPCR. Results: The IGS was significantly (p<0.01) correlated with galectin-9 (rho=0.54) and CXCL10 (rho=0.37) levels whereas serum IFN-α correlated with galectin-9 (rho=0.36), CXCL10 (rho=0.39), CCL19 (rho=0.26) and CCL2 (rho=0.19). The strongest correlation was observed between galectin-9 and TNF (rho=0.56). IFN-α and disease activity (SLEDAI-2K) were correlated (rho=0.20) at cross-sectional analysis, but no significant associations were found between SLEDAI-2K and galectin-9 or chemokines. Several inflammatory mediators increased at disease exacerbation although CCL19, CXCL11, CXCL10, IL-10 and IL-1 receptor antagonist were most pronounced. Immune complex-stimulation of PBMC increased the production of CCL2, CXCL8 and TNF. Conclusion: Galectin-9 and CXCL10 were associated with type I IFN in SLE but correlated stronger with TNF. None of the investigated biomarkers showed a convincing association with disease activity, although CXCL10 and CCL19 performed best in this regard.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biomarker, chemokine, disease activity, galectin, interferon, lupus, SLE, TNF
in
Frontiers in Immunology
volume
12
article number
688753
publisher
Frontiers Media S. A.
external identifiers
  • pmid:34276678
  • scopus:85110088639
ISSN
1664-3224
DOI
10.3389/fimmu.2021.688753
language
English
LU publication?
yes
id
1f3f8d1e-37de-48e4-9a89-71dea3e317b7
date added to LUP
2022-03-21 17:00:14
date last changed
2024-06-05 08:52:22
@article{1f3f8d1e-37de-48e4-9a89-71dea3e317b7,
  abstract     = {{<p>Objectives: Type I interferons (IFNs) are central and reflective of disease activity in systemic lupus erythematosus (SLE). However, IFN-α levels are notoriously difficult to measure and the type I IFN gene signature (IGS) is not yet available in clinical routine. This study evaluates galectin-9 and an array of chemokines/cytokines in their potential as surrogate markers of type I IFN and/or SLE disease activity. Methods: Healthy controls and well-characterized Swedish SLE patients from two cross-sectional cohorts (n=181; n=59) were included, and a subgroup (n=21) was longitudinally followed. Chemokine/cytokine responses in immune complex triggered IFN-α activity was studied in healthy donor peripheral blood mononuclear cells (PBMC). Levels of chemokines/cytokines and galectin-9 were measured by immunoassays. Gene expression was quantified by qPCR. Results: The IGS was significantly (p&lt;0.01) correlated with galectin-9 (rho=0.54) and CXCL10 (rho=0.37) levels whereas serum IFN-α correlated with galectin-9 (rho=0.36), CXCL10 (rho=0.39), CCL19 (rho=0.26) and CCL2 (rho=0.19). The strongest correlation was observed between galectin-9 and TNF (rho=0.56). IFN-α and disease activity (SLEDAI-2K) were correlated (rho=0.20) at cross-sectional analysis, but no significant associations were found between SLEDAI-2K and galectin-9 or chemokines. Several inflammatory mediators increased at disease exacerbation although CCL19, CXCL11, CXCL10, IL-10 and IL-1 receptor antagonist were most pronounced. Immune complex-stimulation of PBMC increased the production of CCL2, CXCL8 and TNF. Conclusion: Galectin-9 and CXCL10 were associated with type I IFN in SLE but correlated stronger with TNF. None of the investigated biomarkers showed a convincing association with disease activity, although CXCL10 and CCL19 performed best in this regard.</p>}},
  author       = {{Enocsson, Helena and Wetterö, Jonas and Eloranta, Maija Leena and Gullstrand, Birgitta and Svanberg, Cecilia and Larsson, Marie and Bengtsson, Anders A. and Rönnblom, Lars and Sjöwall, Christopher}},
  issn         = {{1664-3224}},
  keywords     = {{biomarker; chemokine; disease activity; galectin; interferon; lupus; SLE; TNF}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Comparison of Surrogate Markers of the Type I Interferon Response and Their Ability to Mirror Disease Activity in Systemic Lupus Erythematosus}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2021.688753}},
  doi          = {{10.3389/fimmu.2021.688753}},
  volume       = {{12}},
  year         = {{2021}},
}