POS0189 SERUM IFNα CONCENTRATIONS MEASURED WITH SINGLE-MOLECULE ARRAY TECHNOLOGY IN SJÖGREN’S SYNDROME REFLECT BLOOD INTERFERON-STIMULATED GENE EXPRESSION
نویسندگان
چکیده
Background: Type I interferon (IFN-I) activation is a prominent feature of several Rheumatic and Musculoskeletal Diseases (RMDs) including primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE) sclerosis (SSc). Ultrasensitive single-molecule array (SiMoA) technology has facilitated the measurement subfemtomolar concentrations IFNs [1-3]. Objectives: Here, we tested performance commercially available SiMoA kit for detection IFNα in serum from pSS, SLE, SSc correlated to whole blood IFN-stimulated gene (ISG) expression. Methods: Serum IFNα2 was measured healthy controls (HC; n=68) patients with pSS (n=85, n=110), SLE (n=24) (n=23) using ready-to-use on HD-X Analyzer. IFN-I additionally determined paired samples expression IFI44, IFI44L, IFIT1, IFIT3, MxA by RT-PCR or MxA-ELISA. Results: levels were elevated (median = 61.3 fg/mL) compared HC < 5fg/mL) 11.6 fg/mL), lower 313.5 positively ISG (rs=0.71-0.76, p<0.001). Comparable MxA-ELISA (AUC=0.93), identified high (AUC=0.90) 80-93% specificity 71-84% sensitivity. Blinded validation an independent cohort yielded comparable accuracy 89%. Multiple linear regression indicated associations autoantibodies, IgG, use hydroxychloroquine pSS. Confirming literature [4], remission (DORIS classification) not remission. Conclusion: Thus, reflects SSc. In light IFN-targeting treatments, could potentially be applied patient stratification high-throughput retrospective analysis stored clinical trial material. References: [1]Rissin, D.M.; Kan, C.W.; Campbell, T.G.; Howes, S.C.; Fournier, D.R.; Song, L.; Piech, T.; Patel, P.P.; Chang, Rivnak, A.J., et al. Single-molecule enzyme-linked immunosorbent assay detects proteins at concentrations. Nat. Biotechnol. 2010, 28, 595-599. [2]Wilson, D.H.; Rissin, Meyer, R.E.; Fishburn, M.W.; Cabrera, C.; P.P., The Simoa HD-1 Analyzer: A Novel Fully Automated Digital Immunoassay Analyzer Single-Molecule Sensitivity Multiplexing. Journal Laboratory Automation 2015, 21, 533-547. DOI: 10.1177/2211068215589580. [3]Rodero, M.P.; Decalf, J.; Bondet, V.; Hunt, D.; Rice, G.I.; Werneke, S.; McGlasson, S.L.; Alyanakian, M.A.; Bader-Meunier, B.; Barnerias, C., Detection alpha protein reveals differential cellular sources disease. J. Exp. Med. 2017, 214, 1547-1555. 10.1084/jem.20161451. [4]Mathian, A.; Mouries-Martin, Dorgham, K.; Devilliers, H.; Yssel, Garrido Castillo, Cohen-Aubart, F.; Haroche, Hie, M.; Pineton de Chambrun, M., interferon-alpha quantification during identifies risk relapse. Ann. Rheum. Dis. 2019, 78, 1669-1676. 10.1136/annrheumdis-2019-215571. Disclosure Interests: None declared
منابع مشابه
Extremes of Interferon-Stimulated Gene Expression Associate with Worse Outcomes in the Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome (ARDS) severity may be influenced by heterogeneity of neutrophil activation. Interferon-stimulated genes (ISG) are a broad gene family induced by Type I interferons, often as a response to viral infections, which evokes extensive immunomodulation. We tested the hypothesis that over- or under-expression of immunomodulatory ISG by neutrophils is associated with...
متن کاملBacteria-Specific Neutrophil Dysfunction Associated with Interferon-Stimulated Gene Expression in the Acute Respiratory Distress Syndrome
Acute respiratory distress syndrome (ARDS) is a poorly understood condition with greater than 30% mortality. Massive recruitment of neutrophils to the lung occurs in the initial stages of the ARDS. Significant variability in the severity and duration of ARDS-associated pulmonary inflammation could be linked to heterogeneity in the inflammatory capacity of neutrophils. Interferon-stimulated gene...
متن کاملcomparison of blood flow velocity changes in posterior cerebral artery measured with transcranial doppler sonography in migraineurs with visual aura and normal persons after photostimulation
چکیده ندارد.
15 صفحه اولA single molecule view of gene expression.
Analyzing the expression of single genes in single cells appears minimalistic in comparison to gene expression studies based on more global approaches. However, stimulated by advances in imaging technologies, single-cell studies have become an essential tool in understanding the rules that govern gene expression. This quantitative view of single-cell gene expression is based on counting mRNAs i...
متن کاملSingle-molecule approaches to stochastic gene expression.
Both the transcription of mRNAs from genes and their subsequent translation into proteins are inherently stochastic biochemical events, and this randomness can lead to substantial cell-to-cell variability in mRNA and protein numbers in otherwise identical cells. Recently, a number of studies have greatly enhanced our understanding of stochastic processes in gene expression by utilizing new meth...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Annals of the Rheumatic Diseases
سال: 2021
ISSN: ['1468-2060', '0003-4967']
DOI: https://doi.org/10.1136/annrheumdis-2021-eular.2056