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THU0538 Association of Interleukin-27 Elevation with Abnormal B Cell Functions in Patients with Sjogren's Syndrome
  1. L. Zhang,
  2. C. Zhao,
  3. R. Liu,
  4. X. Li,
  5. X. Feng,
  6. L. Sun
  1. Department of Rheumatology, The Affiliated Drum Tower hospital of Nanjing University Medical School, Nanjing, China

Abstract

Background Interleukin (IL)-27 is a new member of IL-6/IL-12 family involved in isotype switching and plasma cell differentiation of naïve B cells.

Objectives The objective of this study is to investigate the association of IL-27 with B cell functions in patients with Sjogren's syndrome (SS), an autoimmune disease characterized by B-cell hyperactivity.

Methods B cell activation was measured by the percentages of CD40 and CD69 positive cells in total CD19+ B cells under flow cytometry. Carboxyfluorescein diacetate succinimidyl ester (CFSE) and Annexin V were marked to detect B cell proliferation and apoptosis respectively. CD27 and CD138 were used to identify the trend of CD19+ B cell differentiation. To verify the role of IL-27 on B cell regulation, peripheral blood mononuclear cells (PBMCs) collected from SS patients and healthy controls were stimulated by B cell activators including anti-CD40, recombinant human IL-4, CpG-ODN and F(ab)2 goat anti-human IgM with or without the presence of IL-27 at the concentration of 50ng/ml. 72 or 96 hours later, cells were harvested and detected for B cell activation, proliferation, apoptosis and differentiation. Levels of several cytokines that have been reported to participate in B cell regulation, including IL-27, IFN-γ, IL-10, IL-4 and BAFF, were detected by ELISA.

Results Compared with healthy controls, the percentages of active B cells (CD40 or CD69 positive in total CD19+ B cells) were elevated in SS patients (p both <0.05). B cells from SS patients displayed higher proliferation and apoptosis rate (p both <0.05), and an increased cell differentiation into plasma cells was observed (p<0.05). Serum levels of IL-27 were elevated in SS patients, especially in those with high titers of ANA (197.2±24.48 pg/ml vs. 179.8±9.37 pg/ml, p<0.01) or positive anti-SSA/SSB antibodies. In vitro cultures showed that IL-27 stimulation could increase the percentages of CD40/CD69 and CD138 cells, promote B cell proliferation and IgG secretion. Meanwhile, IL-27 could upregulate several B cell related factors in vitro (484.2±235.9 pg/ml vs. 4718±259.9 pg/ml for IFN-γ, 119.2±39.7 pg/ml vs. 98.58±29.17 for IL-4 and 1711±556.6 pg/ml vs. 1436±660.3 pg/ml for IL-10, p all <0.05).

Conclusions IL-27 elevation contributes to B cell hyperactivity in SS patients. Treatment targeting IL-27 may be promising for the amelioration of this disease.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.2416

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