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Immonoglobulin G4‑related ophthalmic disease (IgG4‑ROD) is a IgG4‑RD and exhibits two main characteristics: Fibrosis that is not necessarily marked histopathologically; and frequent formation of germinal centers (GCs). Follicular B helper T (Tfh) cells are now recognized as the true helper cells for B cells in antibody responses. In the present study, the profile and distribution of Tfh cells in involved tissues from patients with IgG4‑ROD was compared to those of type 1 autoimmune pancreatitis (AIP) and patients with IgG4‑related lymphadenopathy (IgG4‑RL). A total of 7 patients with IgG4‑ROD, 7 patients with type 1 AIP or IgG4‑RL and 7 IgG4‑negative controls were evaluated. The expression of Tfh‑cell immunological proteins, the inducible T‑cell costimulator, B‑cell lymphoma 6 protein, C‑X‑C chemokine receptor type 5 (CXCR5) and interleukin‑21 (IL‑21) in affected tissues was analyzed using immunohistochemical staining and dual immunofluorescence. It was demonstrated that patients with IgG4‑RD exhibited a significantly increased number of CD4+CXCR5+ Tfh cells compared with the IgG4‑negative controls. Furthermore, CD4+CXCR5+ Tfh cells were detected in and outside of GCs in patients with IgG4‑ROD and IgG4‑RLF, whereas CD4+CXCR5+ Tfh cells were randomly distributed in areas demonstrating type 1 AIP. Fewer CD4+CXCR5+ Tfh cells were observed in patients with type 1 AIP compared with patients with IgG4‑ROD and IgG4‑RL. In addition, increased expression of IL‑21 was observed in patients with IgG4‑ROD and IgG4‑RL compared with type 1 AIP. IL‑21 expression was positively correlated with the IgG4/IgG ratio in immunohistochemically‑positive cells. The results of the present study indicate that Tfh cells are involved in the histopathological pathogenesis of IgG4‑RD and may serve a different role in IgG4‑ROD and type 1 AIP. Tfh cells may serve a direct role in the IL‑21‑mediated pathogenesis of IgG4‑ROD.

Frequency and distribution of CD4+CXCR5+ follicular B helper T cells within involved tissues in IgG4-related ophthalmic disease