Background: IgG4-related disease (IgG4RD) is a chronic systemic fibroinflammatory condition characterized by the infiltration of IgG4-secreting plasma cells. However, the specific cellular factors that influencing the differentiation of IgG4-secreting plasma cells remain unclear.

Objectives: This study aims to identify the cells that contribute to the generation of IgG4-secreting plasma cells in IgG4RD. Furthermore, we examine the changes induced by B cell depletion with rituximab.

Methods: Blood samples were collected from six IgG4RD patients at baseline and at 2, 6, 12, 24 and 52 weeks post-rituximab treatment. Control samples were obtained from patients with Sjögren syndrome (SS) and healthy controls (HC). Serum immunoglobulin levels were measured using a Cytometric Bead Assay (CBA), and cell subsets of peripheral blood mononuclear cells (PBMCs) were analyzed via flow cytometry.

Results: At baseline, the proportion of IgG4 ⁺ memory B cells in PBMCs was elevated in IgG4RD patients compared to those in SS and HC groups. The proportion of T follicular helper type 2 (Tfh2) cells was increased in IgG4RD compared to the SS and HC groups. Interestingly, the expression of TIGIT and SLAMF7 on Tfh2 cells was higher in IgG4RD patients than in the SS and HC groups and correlated with the proportion of IgG4 ⁺ memory B cells. The depletion of B cells via rituximab led to a decrease in the proportion of B cells and IgG4 ⁺ memory B cells, which was associated with a reduction in the proportion of Tfh2 cells and in the expression of TIGIT and SLAMF7. Additionally, the proportion of IgG4 ⁺ B cells was declined, under the condition of reduced TIGIT and SLAMF7 expression on Tfh2 cells.

Conclusion: Tfh2 cells play a crucial role in the differentiation of IgG4 ⁺ B cells, with TIGIT and SLAMF7 surface marker expression on Tfh2 cells contributing to this process. Thus, targeting TIGIT and SLAMF7 expression on Tfh2 cells may offer a potential therapeutic option for the treatment of IgG4RD.

REFERENCES: [1] Higashioka K, Ota Y, Maehara T, Moriyama M, Ayano M, Mitoma H, Akahoshi M, Arinobu Y, Horiuchi T, Nakamura S, Akashi K, Niiro Kazuhiko, et el. Association of circulating SLAMF7+ Tfh1 cells with IgG4 levels in patients with IgG4-related disease. BMC Immunol. 2020 Jun 1;21(1):31.

[2] Mitsuhiro A, Yuko K, et el. Recent Advances in Understanding the Role of TIGIT+ Follicular Helper T Cells in IgG4-Related Disease. Immuno 2021, 1(4), 380-390.

[3] Akiyama M, Alshehri W, Ishigaki S, Saito K, Kaneko Y, et el. The immunological pathogenesis of IgG4-related disease categorized by clinical characteristics. Immunol Med 2024, 22:1-13.

[4] Xu J, Zhai J, Zhao J, et el. Pathogenic roles of follicular helper T cells in IgG4-related disease and Implications for potential therapy. Front Immunol 2024, 7;15:1413860.

[5] Heeringa JJ, et al. Expansion of blood IgG4+ B, TH2, and regulatory T cells in patient with IgG4-related disease. J Allergy Clin Immunol 2018.

[6] Mattoo H, Mahajan VS, Della-Torre E, Sekigami Y, Carruthers M, Wallace ZS, et al. De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol 2014; 134:679-87.

[7] Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY. IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol 1998;160: 3555-61.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.