Interferon Type I and T Helper 17: A Dangerous Liaison In Primary Sjögren’s Syndrome?

Zana Brkic¹, Sandra M.J. Paulissen², Cornelia G. van Helden-Meeuwsen³, Naomi I. Maria³, Odilia B.J. Corneth⁴, Nadine Davelaar⁵, Jan Piet van Hamburg⁵, Paul L. Van Daele³, Virgil A. Dalm¹, Martin van Hagen³, Erik Lubberts⁶ and Marjan A. Versnel¹, ¹Erasmus Medical Center, Immunology, Rotterdam, Netherlands, ²Rheumatology, Erasmus Medical Center, Rotterdam, Netherlands, ³Immunology, Erasmus Medical Center, Rotterdam, Netherlands, ⁴Rheumatology and Immunology, Erasmus Medical Center, Rotterdam, Netherlands, ⁵Immunology, Erasmus MC, University Medical Center, Rotterdam, Netherlands, ⁶Erasmus Medical Center, Rheumatology, Rotterdam, Netherlands

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Autoimmunity, cytokines and interferons, Sjogren's syndrome, T cells

Session Information

Title: T-cell Biology in Autoimmune Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose:

The T helper 17 (Th17) cell subset, which produces IL-17A, IL-17F, IL-22 and IL-21, has been implicated in the pathogenesis of primary Sjögren’s syndrome (pSS). The aim of this study was to elucidate a possible link between the Th17 system and another key-player in the pathogenesis of pSS ¯ Interferon (IFN) type I.

Methods:

IFN type I signature was assessed by mRNA expression of IFN type I inducible genes. Th cell populations were analyzed by flow cytometry in peripheral blood of 12 pSS patients positive (IFN+) and 12 patients negative (IFN-) for the IFN type I signature and 12 healthy controls (HC). Cytokine expression by memory Th cells (CD4+CD45RO+) cells and memory CCR6+ Th cells (CD4+CD45RO+CCR6+) cells was assessed.

Results:

Th17 (defined as CD4+CD45RO+CCR6+CCR4+CXCR3-CCR10-) and Treg cell percentages were significantly increased in IFN+ patients compared with IFN- patients and HC. This was accompanied by a significant decrease in Th1 cells in IFN+ patients compared to HC. IL-22 and IL-21 production by memory Th cells and memory CCR6+ cells was higher in IFN+ patients. Interestingly, Th17 cell percentage was significantly correlated with presence of anti-SSA antibodies, hypergammagloblulinemia and elevated expression of monocyte B cell activating factor (BAFF) , all three previously found in IFN type I signature positive patients.

Conclusion:

Here we show for the first time a relation between two key players of pSS pathogenesis − IFN type I and the Th17 pathway. This study brings new insights in the pathogenesis of pSS, having possible implications for future treatment.

Disclosure:

Z. Brkic,
None;

S. M. J. Paulissen,
None;

C. G. van Helden-Meeuwsen,
None;

N. I. Maria,
None;

O. B. J. Corneth,
None;

N. Davelaar,
None;

J. P. van Hamburg,
None;

P. L. Van Daele,
None;

V. A. Dalm,
None;

M. van Hagen,
None;

E. Lubberts,
None;

M. A. Versnel,
None.

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