Reduced follicular helper T cells in peripheral blood marks a distinct feature of retroperitoneal fibrosis

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ID: 315031
2026
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Abstract
OBJECTIVE: Idiopathic retroperitoneal fibrosis (RPF) is considered a "silent disease" due to the lack of distinct disease biomarker. Our purpose was to study characteristic changes in circulating lymphocytes in RPF patients and explore their roles in etiopathogenesis. METHODS: 23 RPF patients were enrolled and followed up for 48 weeks of treatment. Changes of T and B lymphocyte subsets in their peripheral blood were measured, and their associations with disease activity and severity were evaluated. The Proliferation, secretion and chemotactic functions of circulating follicular helper T (cTFH) cells were assessed by flow cytometry and RNA-sequencing following CD4+ T cell sorting. RESULTS: Among the changed lymphocytes, cTFH cells present a distinct pattern compared with other autoimmune conditions. They were significantly reduced in RPF patients but positively correlated with disease severity and TFH expansion in fibrotic tissues. Remarkably, they were further declined upon disease amelioration, indicating their potential as a disease marker. Further investigation revealed unchanged proliferation and low cytokine secretion in these cTFH cells. Instead, chemokine CXCL13 expression was markedly elevated in CD4+ T cells isolated from both fibrotic tissues and peripheral blood of RPF patients, whereas key cytokines IL-21, IL-6, and Bcl were elevated only in the fibrotic tissues. CONCLUSION: Our findings suggest that cTFH cells in the circulating blood of RPF do not expand but may undergo chemotactic migration to fibrotic tissues, marking a distinct feature of RPF and may serve as a potential biomarker.
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Authors H T Gao, Z Li, Shibo Liu, Yuchao Zhong, Ut-kei Wong, Tian Wang, Guoqiang Lu, Yingxi Zhu, Wei Zhao, Jinxia Zhao, Xiaoying Zhang, Chenghua Luo, J S He, X Y Zhang, Cuiping Pan, Z Li
Journal Lara D. Veeken
Year 2026
DOI
10.1093/rheumatology/keag274
URL
https://doi.org/10.1093/rheumatology/keag274
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