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Serum IFNα2 measure...
Serum IFNα2 measured by single-molecule array associates with systemic disease manifestations in Sjögren's syndrome
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- Huijser, Erika (författare)
- Erasmus University Medical Center
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- Göpfert, Jens (författare)
- University of Tübingen
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- Brkic, Zana (författare)
- Erasmus University Medical Center
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- van Helden-Meeuwsen, Cornelia G (författare)
- Erasmus University Medical Center
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- Jansen, Sanne (författare)
- Erasmus University Medical Center
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- Mandl, Thomas (författare)
- Lund University,Lunds universitet,Reumatologi,Forskargrupper vid Lunds universitet,Rheumatology,Lund University Research Groups
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- Olsson, Peter (författare)
- Lund University,Lunds universitet,Reumatologi,Forskargrupper vid Lunds universitet,Rheumatology,Lund University Research Groups
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- Schrijver, Benjamin (författare)
- Erasmus University Medical Center
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- Schreurs, Marco W J (författare)
- Erasmus University Medical Center
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- van Daele, Paul L A (författare)
- Erasmus University Medical Center
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- Dik, Willem A (författare)
- Erasmus University Medical Center
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- Versnel, Marjan A (författare)
- Erasmus University Medical Center
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(creator_code:org_t)
- 2021-09-10
- 2022
- Engelska.
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 61:5, s. 2156-2166
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://academic.oup...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
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Huijser, Erika
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Göpfert, Jens
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Brkic, Zana
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van Helden-Meeuw ...
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Jansen, Sanne
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Mandl, Thomas
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visa fler...
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Olsson, Peter
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Schrijver, Benja ...
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Schreurs, Marco ...
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van Daele, Paul ...
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Dik, Willem A
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Versnel, Marjan ...
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