OP0080 Lesional IL-21 Expression Correlates with Functional Germinal Center Formation and T Follicular Helper Cell Infiltration in the Salivary Glands of Sjögren’s Syndrome

Background IL-21 is a pro-inflammatory cytokine that plays a key role in the activation and differentiation of B cells 1 . B cells infiltrate the salivary glands (SG) of Sjogren’s syndrome (SS), an autoimmune disease characterized by immune infiltration in the lacrimal and salivary glands leading to exocrine dysfunction 2 . In SS SG, B cells are organized as functional ectopic germinal centers (GC) and are pivotal in SS pathogenesis 3 . Follicular helper T cells (Tfh) abundantly express IL-21 and contribute to GC B cell affinity maturation via induction of AID, somatic hypermutation and class switching 4 . Objectives We aimed to investigate IL-21 mRNA expression in SS SG, to correlate expression with markers of inflammation such as CXCL13, Ltb, BAFF as well as markers of B cell differentiation AID, Pax5 and Blimp1, and then to assess the relationship of IL-21 and Tfh cells with the development of functional ectopic GC. Methods IL-21 and IL-21R mRNA expression was assessed by Taqman PCR in 22 labial SG of patients with SS and 17 with non-specific chronic sialadenitis (NSCS). Expression levels were correlated with genes regulating ectopic GC formation such as CXCL13 and Ltb and B cell function such as BAFF, AID, Pax5 and Blimp1. In addition, GC formation in the SG was assessed by IHC for B/T cell segregation and follicular dendritic cell (FDC) networks. Finally, Tfh cells infiltration in the SG was assessed by IF for CD3/CD45RO/ICOS and PD1. Results SG of SS patients displayed higher expression of IL-21 and IL-21R mRNA compared to NSCS (mean fold increase±SEM 38±12 vs 5±4, p=0.02 for IL-21 and 59±13 vs 12±2, p=0.01). In SS, IL-21 mRNA strictly correlated with the levels of CXCL13 (Spearman’s r=0.697, p Conclusions Here we show that IL-21 expression is significantly increased in the SG of SS patients and strongly correlates with ectopic GC formation, functional B cell activation and accumulation of Tfh. These data strongly implicate IL-21 and Tfh cells in the development and maintenance of functional ectopic GC in the SG and could represent novel therapeutic targets in SS. References Mehta, D. S., et al. , (2004). Immunological Reviews Christodoulou, M. I., et al., (2010) . Journal of Autoimmunity Barone, F., et al., (2005) . Arthritis and Rheumatism Crotty, S. (2011) . Annual Review of Immunology Disclosure of Interest None Declared