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Abstract Number: 643

Potential Immunopathological Roles Of The Novel Anti-Inflammatory Cytokine Interleukin-35 In Patients With Systemic Lupus Erythematous

Zhe Cai1, Chun-Kwok Wong2 and Lai Shan Tam3, 1The Chinese University of Hong Kong, Hong Kong, Hong Kong, 2Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, 3Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: cytokines, pathogenesis and systemic lupus erythematosus (SLE)

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Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Mechanisms and Biomarkers

Session Type: Abstract Submissions (ACR)

Background/Purpose:

IL-35, a dimeric protein with two subunits, IL-12A (p35) and Epstein-Barr virus induced 3, is a novel IL-12 cytokine family regulatory T-cells (Treg)-specific immunosuppressive/anti-inflammatory cytokine. IL-35 is expressed by resting and activated regulatory T cells (Tregs/Tr35) by converting conventional T cells (Tconv) into IL-35-dependent induced Tregs (iTr35), but not effector T (Teff) cells.  Similar to that of transforming growth factor-b and IL-10, IL-35 is the major component of the suppressive repertoire, but temporally different from them in the inhibition of inflammation. We hypothesize that IL-35 may play an important immunoregulatory roles in autoimmune diseases such as systemic lupus erythematous (SLE).

Methods:

Plasma concentrations of IL-35 and soluble gp130 were measured using ELISA. Cell surface expression of IL-35 receptor components IL-12Rb2 and gp130 on the CD4+ helper (Th) cells and CD19+ B cells, and the number of CD4+CD25highCD127lowTreg cells were quantitated by flow cytometry.

Results:

Plasma IL-35 levels were significantly higher in active SLE patients than healthy controls (HC).  Percentages of Treg in active and inactive SLE patients were significantly higher than HC. The percentage of Treg in active SLE patient was significantly higher than in inactive SLE patients (all p < 0.05). Moreover, the percentage of Treg cells was positively correlated with the SLE disease activity index (SLEDAI), but it did not correlate with the expression of IL-12Rb2 and gp130 on Th and B cells. However, the expression of IL-12Rb2 on the Th cells and B cells of inactive and active SLE patients, respectively, was significantly higher than HC.   

Conclusion:

The above results may imply the potential immunological roles of anti-inflammatory cytokine IL-35 receptors. Since IL-35 receptor components IL-12Rb2 played the key role in the signaling transduction of the immunosuppressive mechanisms of the IL-35 in SLE immunopathogenesis, results of this cross-sectional clinical study may also furnish a biochemical basis for the development of potential therapeutic target of IL-35 for the treatment of autoimmune inflammation.


Disclosure:

Z. Cai,
None;

C. K. Wong,
None;

L. S. Tam,
None.

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