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

Yang,Huimin; Wei,Ruili; Liu,Qiang; Shi,Yongheng; Li,Jin

doi:10.3892/mmr.2017.7780

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

Authors:
- Huimin Yang
- Ruili Wei
- Qiang Liu
- Yongheng Shi
- Jin Li
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Affiliations: Department of Ophthalmology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, P.R. China, Department of Ophthalmology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Pathology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
Published online on: October 12, 2017 https://doi.org/10.3892/mmr.2017.7780
Pages: 9512-9520
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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