OP0100 Indoleamine 2,3 Dioxygenase I Expression in Sjogren's Sialoadenitis Correlates with the Local Amount of B-Lymphocytes and Plasmocytoid Dendritic Cells
Authors: C. Vitali, A. Parafioriti, D. Sambataro, A. Di Bernardo, E. Ammiraglio, J. Campos, F. Barone, N. Del Papa
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Indoleamine 2,3 dioxygenase 1 and 2 (IDO1-IDO2) enzymes catabolise tryptophan (TR) to its metabolite kyurenine (KNR), and are competitively inhibited by 1-Methyl-TR (1M-TR). IDO1-IDO2, once activated in dendritic cells (DCs) by IFN-type 1, may induce immune-tolerance by suppressing antigen-specific T-cell response directly or by activating T-reg cells [1]. The role of IDO in autoimmune diseases has not been completely elucidated. In collagen-induced arthritis of DBA/1 mice, IDO1 limits the arthritis phenotype, as shown by the detrimental effect of 1M-TR treatment. Conversely, in auto-reactive B-cell-mediated arthritis of K/BxN transgenic mice, IDO1 sustains the autoimmune aggression, as demonstrated by arthritis improvement and auto-reactive B-cell reduction in draining lymph nodes after 1M-TR treatment [2]. Finally, significantly increased plasma KNR levels and KNR/TR ratio have been reported in patients with systemic lupus and Sjogren9s syndrome (SS) [2]. <h3>Objectives</h3> To verify whether IDO1 is activated in SS focal sialoadenitis (FS), and investigate the relationships between IDO1 expression and the main cellular components in inflammatory foci. <h3>Methods</h3> Minor salivary gland biopsies from 22 patients (1 male, 21 females) with SS were examined for IDO1 expression using anti-IDO1 antibodies (Abs), and immuno-histochemistry (IHC). Prevalence of B-cells, T-cells, and plasmacytoid (p) DCs was investigated in FS infiltrates using monoclonal anti-CD20, -CD3, and -CD123 Abs, respectively. Immuno-fluorescence (IF) was used to evaluate the co-localization of IDO1+ cells with the immune cells within SS FS. <h3>Results</h3> Patients were aged 15-77 yrs. (mean 53.4 yrs), and their disease duration ranged from 1 to 16 yrs. (mean 8.9 yrs.). Anti-Ro/La Abs and extra-glandular features were recorded in 15 and 14 patients, respectively. IHC analysis demonstrated consistent expression of IDO1 within the focal infiltrates. A semi-quantitative IHC score showed significant correlation between IDO1 expression and FS scores (Spearman R=0.52, p&lt;.02), prevalence of CD20+B-cells (R=0.79, p&lt;.0005), and number of CD123+pDCs (R=0.64, p&lt;.005), but not with the CD3+T-cells (R=0.14, p=ns). IF analysis of FS infiltrates characterized by germinal centre-like organization demonstrated presence of IDO1+ cells around the B-cell area and at the boundaries of the T cell rich zone. <h3>Conclusions</h3> IDO1 activity is present in SS FS, and appears to be related to the amount of pDCs and B-cells. Further investigations are needed to clarify the cell type(s) expressing IDO1 within the SS FS infiltrates and the immuno-regulatory role of this enzyme in SS. <h3>References</h3> Johnson BA, et al. Immunotherapy 2009;1:645. Filippini P, et al. Curr Med Chem. 2012;19:5381. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3150