Serum IFNα2 measured by single-molecule array associates with systemic disease manifestations in Sjögren's syndrome
(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.
(Less)
- author
- organization
- publishing date
- 2022
- 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
-
- scopus:85129998312
- pmid:34505866
- 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 < 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.</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}},
}