OP0115 Increased T Follicular Helper Subset 2 Related to Increased IGG4 and Plasmablasts Through IL-4 in IGG4-Related Disease

Background Immunoglobulin (Ig) G4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration of IgG4 + plasma cells 1 . B cells producing excessive IgG4 is one of the diagnostic immunological feature of IgG4-RD. T follicular helper cells (Tfh) is the distinct subset of CD4 + T cells that has been recognized to help B cell differentiation. Recently, Tfh subset: Tfh1, Tfh2, and Tfh17 was newly recognized based on different expression pattern of CXCR3 and CCR6. The skewed Tfh subset was reported to correlate with disease activity in autoimmune diseases. However, the role of Tfh and its subsets in IgG4-RD remains unclear. Objectives Elucidate the role of Tfh and its subsets in active, untreated IgG4-RD. Methods Peripheral blood from 15 active, untreated, biopsy-proven IgG4-RD patients, 24 primary Sjogren9s Syndrome (pSS), 12 allergic rhinitis (AR), and 23 healthy controls (HC) were evaluated. Tfh was defined as CD3 + CD4 + CXCR5 + CD45RA - and was subdivided into three subsets (Tfh1, Tfh2, and Tfh17) based on the expression of CXCR3 and CCR6. CD19 + CD20 - CD27 + CD38 + cells were defined as plasmablasts. Results IgG4-RD patients had significantly increased proportion of Tfh compared to AR and HC. Among Tfh subsets, Tfh2 was specifically increased in IgG4-RD compared to pSS, AR and HC, whereas Tfh1 and Tfh17 resulted in non-statistical difference. Increased Tfh2 strongly correlated with serum IgG4, IgG4/IgG ratio and proportion of plasmablast in IgG4-RD (ρ =0.892, p Conclusions Our results suggest that Tfh2 plays a crucial role in IgG4 production and generation of plasmablasts in IgG4-RD. In addition, IL-4 seemed to be the key cytokine for increased Tfh2, plasmablast and IgG4. More interestingly, IgG4 and plasmablast but not Tfh2 decreased after treatment with GCs suggesting Tfh2 as the underlying pathological T cell subset and as a potential therapeutic target for IgG4-RD. References Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 2012;22:21-30. Acknowledgements We thank all the patients and healthy individuals that participated this study. We specially thank Ms. Yoshiko Yogiashi and Ms. Yuki Ootomo for their technical assistance. Disclosure of Interest None declared