Aberrant Cell Signaling in Peripheral Blood Mononuclear Cells upon Interferon Alpha Stimulation in Patients with Primary Sjögren’s Syndrome Associates with Type I Interferon Signature

Richard Davies¹, Daniel Hammenfors^1,2, Brith Bergum¹, Petra Vogelsang¹, Sonia Gavasso³, Johan G. Brun^2,4, Roland Jonsson^5,6 and Silke Appel¹, ¹Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway, ²Department of Rheumatology, Haukeland University Hospital, Bergen, Norway, ³Department of Neurology, Haukeland University Hospital, Bergen, Norway, ⁴Department of Clinical Science, University of Bergen, Bergen, Norway, ⁵Broegelmann Research laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway, ⁶Department of Rheumatology, Haukeland University Hospital, Bergen, Bergen, Norway

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: Cell Signaling, Sjogren's syndrome and interferons

Session Information

Date: Monday, November 6, 2017

Title: Innate Immunity and Rheumatic Disease Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Primary Sjögren’s syndrome (pSS) is a complex heterogeneous systemic autoimmune disease. Biomarkers for patient stratification are scarce. Several single nucleotide polymorphisms within type I interferon (IFN) signaling pathways are associated with pSS. To define novel biomarkers for pSS patient stratification, we analyzed the temporal profile of MAPK/ERK and JAK/STAT signalling networks in PBMCs upon stimulation with IFNα by flow cytometry.

Methods: PBMCs from pSS patients and healthy matched donors were stimulated for 15, 30, 60, 120, 180, and 240 min with IFNα at 100 ng / ml. Nine different phospho epitopes were measured, STAT4(pY693), ERK1/2(pT202/pY204), NF-κB p65(pS529), STAT1(pS727), STAT1(pY701), p38 MAPK(pT180/pY182), STAT3(pS727), STAT3(pY705) and STAT5(pY694). Cell surface markers were CD3, CD20 and CD56.

Results: Cells from pSS patients display significant differences in basal and IFNα induced phosphorylation levels of numerous signaling proteins compared to cells from healthy donors. PCA using IFNα induced phosphorylation levels after 15 minutes showed clustering of pSS patients and pSS patient subgroups. PCA visualization showed a positive shift for pSS samples away from healthy donor samples with positive movement influenced by changes in phosphorylation of STAT1 Y701 in T, NK and B cells in PC1, and PC2 positive movement influenced by STAT1 Y701 in NK and B cells, and negative movement by STAT3 S727 in T cells. Medicated and SSA- patients grouped closer to healthy donors than non-medicated or SSA+ patients.

Conclusion: pSS patients show increased responses to IFNα through STAT1. Increased responses to IFNα may in part drive an up-regulation of interferon induced genes.

Disclosure: R. Davies, None; D. Hammenfors, None; B. Bergum, None; P. Vogelsang, None; S. Gavasso, None; J. G. Brun, None; R. Jonsson, None; S. Appel, None.

To cite this abstract in AMA style:

Davies R, Hammenfors D, Bergum B, Vogelsang P, Gavasso S, Brun JG, Jonsson R, Appel S. Aberrant Cell Signaling in Peripheral Blood Mononuclear Cells upon Interferon Alpha Stimulation in Patients with Primary Sjögren’s Syndrome Associates with Type I Interferon Signature [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/aberrant-cell-signaling-in-peripheral-blood-mononuclear-cells-upon-interferon-alpha-stimulation-in-patients-with-primary-sjogrens-syndrome-associates-with-type-i-interferon-signature/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/aberrant-cell-signaling-in-peripheral-blood-mononuclear-cells-upon-interferon-alpha-stimulation-in-patients-with-primary-sjogrens-syndrome-associates-with-type-i-interferon-signature/