ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1826

STAT3 Phosphorylation Mediates the Stimulatory Effects of Interferon Alpha on B Cell Differentiation and Activation in SLE

Julie Ducreux1, Floor Aleva2, Aurelie Degroof3, Alina Ferster4, Andre van der Ven2, Frank van de Veerdonk2, Frédéric A. Houssiau1 and Bernard R. Lauwerys1, 1Pôle de pathologies rhumatismales inflammatoires et systémiques, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium, 2Department of General Internal Medicine, Radboud University, Nijmegen, Netherlands, 3Pôle de Maladies Rhumatismales, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium, 4Service d'Onco-Hématologie, Hôpital Reine Fabiola, Brussels, Belgium

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: ,

Session Information

Date: Monday, November 14, 2016

Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis - Poster I

Session Type: ACR Poster Session B

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

Background/Purpose:  In our previous work, we reported a link between interferon alpha inhibition and decreased expression of B cell activation genes in ex vivo whole blood samples from interferon kinoid-treated SLE patients. Here, we investigated the mechanisms underlying the effects of interferon alpha on B cell activation and differentiation.

Methods:  PBMC and purified total (CD20+) or naïve (CD19+ CD20+ IgD+ CD27-) B cells were obtained from healthy controls and SLE patients. The effects of interferon alpha on B cell differentiation were studied by flow cytometry. STAT1 and STAT3 phosphorylation in CD20+ B cells (9 SLE and 5 control individuals) was evaluated by Western Blot. The role of STAT3 on B cell responses to interferon alpha was studied using pharmacological inhibitors (STA21 and S31201) and PBMC from STAT3-deficient individuals (n=5).

Results: Spontaneous levels of STAT3, but not STAT1, phosphorylation were significantly higher in total B cells from SLE patients compared to controls. In purified naïve B cells from controls, interferon alpha induced STAT1 and STAT3 phosphorylation. Interferon alpha also displayed direct stimulatory effects on purified naïve B cells from healthy individuals, as evidenced by a significant induction of cell surface CD38 and CD95 in the presence of the cytokine. Incubation of normal PBMC with interferon alpha induced a B cell differentiation pattern as observed spontaneously in SLE PBMC: decreased naïve, decreased unswitched memory, increased switched memory cells and increased plasmablasts. In addition, expression of cell surface CD95 was significantly induced by interferon alpha in all these B cell sub-populations, except in plasmablasts (unstimulated plasmablasts highly express CD95). Interferon alpha-induced B cell differentiation in total PBMC was significantly inhibited in the presence of STAT3 inhibitors, or in PBMC from STAT3-deficient patients.

Conclusion:  Interferon alpha displays direct stimulatory effects on B cell differentiation and activation in SLE. STAT3 phosphorylation mediates the effects of interferon alpha stimulation in naïve B cells, an observation that opens new therapeutic perspectives in SLE.

Disclosure: J. Ducreux, None; F. Aleva, None; A. Degroof, None; A. Ferster, None; A. van der Ven, None; F. van de Veerdonk, None; F. A. Houssiau, None; B. R. Lauwerys, None.

To cite this abstract in AMA style:

Ducreux J, Aleva F, Degroof A, Ferster A, van der Ven A, van de Veerdonk F, Houssiau FA, Lauwerys BR. STAT3 Phosphorylation Mediates the Stimulatory Effects of Interferon Alpha on B Cell Differentiation and Activation in SLE [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/stat3-phosphorylation-mediates-the-stimulatory-effects-of-interferon-alpha-on-b-cell-differentiation-and-activation-in-sle/. Accessed .

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