SAT0006 T-CELL IMMUNOGLOBULIN AND MUCIN DOMAIN 3 (TIM-3) IS INCREASED IN ACTIVE RHEUMATOID ARTHRITIS AND ASSOCIATED WITH CLINICAL DISEASE ACTIVITY AND RADIOGRAPHIC PROGRESSION

Abstract

Background: Co-inhibitory receptors are important for the regulation of inflammation in autoimmune diseases. Among these, T-cell Immunoglobulin and mucin domain-3 (Tim-3) has recently gained attention, as it is expressed on exhausted T cells co-expressing PD-1 (1). Objectives: To investigate Tim-3’s role in rheumatoid arthritis (RA). Methods: Early RA (eRA) patients were randomized to conventional methotrexate (MTX) treatment + placebo or MTX + adalimumab (ADA) (2). Plasma were analysed by ELISA at baseline (n=98) and after 3 and 12 months of treatment. Clinical follow up including 28-joint Disease Activity Score with CRP (DAS28CRP) and Total Sharp Score (TSS) were available. Intrasubject differences in sTim-3 between baseline and 3 months were assessed by parametric paired t tests and compared with plasma from HV (n=44) by parametric unpaired t tests. Spearman correlation and Mann-Whitney test were used to investigate relations between sTim-3 and clinical follow up. From chronic RA (cRA) patients (n=17) plasma and synovial fluid were analysed by ELISA and peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) (n=8) were analysed by flow cytometry. Intrasubject differences were assessed by paired parametric t tests, and comparison with PBMC from HV (n=6) by unpaired parametric t test. Parametric data are reported as mean differences (MD) [95%CI]. P values Results: Among memory prone T cells (CD3+CD4+CD45RO+) in SFMC, the percentage of Tim-3+ cells were increased compared with similar gated PBMC from patients (MD 17.4%, [10.7;24.1], p Conclusion: Tim-3 expression is upregulated in memory prone T cells in RA joints and the majority co-express PD-1. Levels of sTim-3 are increased in SF. In eRA, baseline sTim-3 plasma levels are elevated and correlate with DAS28CRP. Decrease of sTim-3 during treatment associates with future radiographic progression. We suggest, that Tim-3 expression and sTim-3 plasma and SF levels reflect ongoing immune response, thus immune regulation in RA. These data indicate that maintenance of sTim-3 plasma levels during treatment is favourable, consistent with Tim-3 being a co-inhibitory receptor. Reference [1] Ana C. et al. Immunity 2016;44:989-1004, 2 Horslev-Petersen K, et al. Ann Rheum Dis 2014;73:654-661. Disclosure of Interests: Caecilie Skejo: None declared, Morten Aagaard Nielsen: None declared, Malene Hvid: None declared, Aida Solhoj Hansen: None declared, Kristian Stengaard-Pedersen: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Kim Horslev-Petersen: None declared, Peter Junker: None declared, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Stinne Ravn Greisen: None declared, Mette Deleuran: None declared, Bent Deleuran: None declared