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Abstract Number: 531

Expression of Indoleamine 2,3 Dioxygenase-1 and -2 in Focal Sialoadenitis of Patients with Sjögren’s Syndrome

Claudio Vitali1, Antonina Prafioriti2, Domenico Sambataro3, Andrea Di Bernardo2, Elisabetta Admiraglio2, Saba Nayar4, Francesca Barone4 and Nicoletta Del Papa3, 1Rheumatology Section, Istituto San Giuseppe, Como, Italy, 2Pathology Unit, Istituto G.Pini, Milan, Italy, 3Rheumatology Unit, Istituto G.Pini, Milan, Italy, 4Rheumatology Research Group, University of Birmingham Research Laboratories, University of Birmingham, Birmingham, United Kingdom

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Immune regulation, Sjogren's syndrome and sialoadenitis

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Session Information

Title: Sjogren's Syndrome: Pathophysiology

Session Type: Abstract Submissions (ACR)

Background/Purpose

The role of indoleamine 2,3 dioxygenase 1 and 2 (IDO1-IDO2) enzymes in modulating the immune response has not been so far completely clarified. IDO1 may induce immune-tolerance by suppressing antigen-specific T-cell response, directly or by activating T-reg cells, as shown in some cancer cells and in the placental tissue.  IDO1 and IDO2 function in autoimmune diseases is controversial. In collagen-induced arthritis of DBA/1 mice, IDO1 limits the arthritis phenotype, as suggested by arthritis worsening after IDO1 inhibition. Conversely, IDO2 is critical for arthritis development in K/BxN transgenic mice, since IDO2-null mice display less aggressive joint inflammation.

This study was aimed at investigating whether IDO1/IDO2 are expressed in focal sialoadenitis of Sjögren’s syndrome (SS), and possibly at identifying the inflammatory cells where these enzymes are active.

Methods

Minor salivary gland biopsies from 22 patients (21 F) with SS (according to the AECG classification criteria) were examined for IDO1 and IDO2 expression by using monoclonal antibodies, and immuno-histochemical (IH) and immuno-fluorescence (IF) methods. In IH-stained sections the prevalence (or number) of CD3+T-cells, CD20+B-cells, CD123+dendritic cells (DC), IDO+cells was semi-quantitatively scored. Co-localization of IDO+cells and of the other inflammatory cells was investigated by IF methods

Results

IH studies showed that IDO1 was notably expressed within the focal infiltrates.  Correlations were found between the amount of IDO1+cells and the focus score (R=0.52, p<0.02),  the prevalence of B-cells (R=0.79, p<0.0005), and  the number of DCs (R=0.64, p<0.005).  IDO2 was expressed in the vessel walls and ductal cells surrounded by infiltrates, but not in the CD3+T-cell area.

In germinal centre-like foci, IF studies showed that IDO1+cells were noticed around the B-cell area, at the boundaries of the T-cell zone. IDO2 was expressed only in a part of samples within the B-cell area, and in both CD138+plasma cells and CD68+macrophages.

Conclusion

In focal infiltrates of patients with SS, different areas and different cells may express IDO1 and IDO2 enzymes, thus suggesting that activity and function of these molecules in this context could be different.


Disclosure:

C. Vitali,
None;

A. Prafioriti,
None;

D. Sambataro,
None;

A. Di Bernardo,
None;

E. Admiraglio,
None;

S. Nayar,
None;

F. Barone,
None;

N. Del Papa,
None.

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