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Serum IFNα2 measured by single-molecule array associates with systemic disease manifestations in Sjögren's syndrome

Huijser, Erika ; Göpfert, Jens ; Brkic, Zana ; van Helden-Meeuwsen, Cornelia G ; Jansen, Sanne ; Mandl, Thomas LU ; Olsson, Peter LU ; Schrijver, Benjamin ; Schreurs, Marco W J and van Daele, Paul L A , et al. (2022) In Rheumatology (Oxford, England) 61(5). p.2156-2166
Abstract

OBJECTIVES: Type I IFN (IFN-I) activation is a prominent feature of primary SS (pSS), SLE, and SSc. Ultrasensitive single-molecule array (Simoa) technology has facilitated the measurement of subfemtomolar concentrations of IFNs. Here, we aimed to measure IFNα2 in serum from pSS, SLE, and SSc using a Simoa immunoassay and correlate these levels to blood IFN-stimulated gene (ISG) expression and disease activity.

METHODS: Serum IFNα2 was measured in patients with pSS (n = 85; n = 110), SLE (n = 24), and SSc (n = 23), and healthy controls (HC; n = 68) using an IFNα Simoa assay on a HD-X analyser. IFN-I pathway activation was additionally determined from serum by an IFN-I reporter assay and paired samples of whole blood ISG expression... (More)

OBJECTIVES: Type I IFN (IFN-I) activation is a prominent feature of primary SS (pSS), SLE, and SSc. Ultrasensitive single-molecule array (Simoa) technology has facilitated the measurement of subfemtomolar concentrations of IFNs. Here, we aimed to measure IFNα2 in serum from pSS, SLE, and SSc using a Simoa immunoassay and correlate these levels to blood IFN-stimulated gene (ISG) expression and disease activity.

METHODS: Serum IFNα2 was measured in patients with pSS (n = 85; n = 110), SLE (n = 24), and SSc (n = 23), and healthy controls (HC; n = 68) using an IFNα Simoa assay on a HD-X analyser. IFN-I pathway activation was additionally determined from serum by an IFN-I reporter assay and paired samples of whole blood ISG expression of IFI44, IFI44L, IFIT1, IFIT3, and MxA by RT-PCR or MxA-ELISA.

RESULTS: Serum IFNα2 levels were elevated in pSS (median=61.3 fg/mL) compared to HC (median ≤5 fg/mL; p < 0.001) and SSc (median=11.6 fg/mL; p = 0.043), lower compared to SLE (median=313.5 fg/mL; p = 0.068), and positively correlated with blood ISG expression (r = 0.66-0.94; p < 0.001). Comparable to MxA-ELISA (AUC=0.93), IFNα2 measurement using Simoa identified pSS with high ISG expression (AUC=0.90) with 80-93% specificity and 71-84% sensitivity. Blinded validation in an independent pSS cohort yielded a comparable accuracy. Multiple regression indicated independent associations of autoantibodies, IgG, HCQ treatment, cutaneous disease and history of extraglandular manifestations with serum IFNα2 concentrations in pSS.

CONCLUSION: Thus, Simoa serum IFNα2 reflects blood ISG expression in pSS, SLE, and SSc. In light of IFN-targeting treatments, Simoa could potentially be applied for patient stratification or retrospective analysis of historical cohorts.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Rheumatology (Oxford, England)
volume
61
issue
5
pages
2156 - 2166
publisher
Oxford University Press
external identifiers
  • pmid:34505866
  • scopus:85129998312
ISSN
1462-0332
DOI
10.1093/rheumatology/keab688
language
English
LU publication?
yes
id
10dabb05-a6f6-40d1-b885-5047c6270b03
date added to LUP
2021-09-24 20:17:20
date last changed
2024-06-29 01:33:52
@article{10dabb05-a6f6-40d1-b885-5047c6270b03,
  abstract     = {{<p>OBJECTIVES: Type I IFN (IFN-I) activation is a prominent feature of primary SS (pSS), SLE, and SSc. Ultrasensitive single-molecule array (Simoa) technology has facilitated the measurement of subfemtomolar concentrations of IFNs. Here, we aimed to measure IFNα2 in serum from pSS, SLE, and SSc using a Simoa immunoassay and correlate these levels to blood IFN-stimulated gene (ISG) expression and disease activity.</p><p>METHODS: Serum IFNα2 was measured in patients with pSS (n = 85; n = 110), SLE (n = 24), and SSc (n = 23), and healthy controls (HC; n = 68) using an IFNα Simoa assay on a HD-X analyser. IFN-I pathway activation was additionally determined from serum by an IFN-I reporter assay and paired samples of whole blood ISG expression of IFI44, IFI44L, IFIT1, IFIT3, and MxA by RT-PCR or MxA-ELISA.</p><p>RESULTS: Serum IFNα2 levels were elevated in pSS (median=61.3 fg/mL) compared to HC (median ≤5 fg/mL; p &lt; 0.001) and SSc (median=11.6 fg/mL; p = 0.043), lower compared to SLE (median=313.5 fg/mL; p = 0.068), and positively correlated with blood ISG expression (r = 0.66-0.94; p &lt; 0.001). Comparable to MxA-ELISA (AUC=0.93), IFNα2 measurement using Simoa identified pSS with high ISG expression (AUC=0.90) with 80-93% specificity and 71-84% sensitivity. Blinded validation in an independent pSS cohort yielded a comparable accuracy. Multiple regression indicated independent associations of autoantibodies, IgG, HCQ treatment, cutaneous disease and history of extraglandular manifestations with serum IFNα2 concentrations in pSS.</p><p>CONCLUSION: Thus, Simoa serum IFNα2 reflects blood ISG expression in pSS, SLE, and SSc. In light of IFN-targeting treatments, Simoa could potentially be applied for patient stratification or retrospective analysis of historical cohorts.</p>}},
  author       = {{Huijser, Erika and Göpfert, Jens and Brkic, Zana and van Helden-Meeuwsen, Cornelia G and Jansen, Sanne and Mandl, Thomas and Olsson, Peter and Schrijver, Benjamin and Schreurs, Marco W J and van Daele, Paul L A and Dik, Willem A and Versnel, Marjan A}},
  issn         = {{1462-0332}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{2156--2166}},
  publisher    = {{Oxford University Press}},
  series       = {{Rheumatology (Oxford, England)}},
  title        = {{Serum IFNα2 measured by single-molecule array associates with systemic disease manifestations in Sjögren's syndrome}},
  url          = {{http://dx.doi.org/10.1093/rheumatology/keab688}},
  doi          = {{10.1093/rheumatology/keab688}},
  volume       = {{61}},
  year         = {{2022}},
}