Extrafollicular Tph2-like cell dominant tissue pathotype is associated with relapse in IgG4-related disease

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ID: 324908
2026
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Abstract
Abstract Objective Relapse is common in IgG4-related disease (IgG4-RD), but reliable predictors to identify high-risk patients remain limited. We sought to identify blood and tissue immune features at the initiation of remission induction therapy associated with subsequent relapse. Methods Seventy-four consecutive, active patients with IgG4-RD were prospectively enrolled in a cohort, and comprehensive immunophenotyping of 64 blood immune subsets was performed. They were followed after remission induction therapy until relapse or last visit. Lacrimal gland biopsy specimens were analyzed using automated image-based quantification to classify tissues as T-B-pathotype or B-pathotype. An independent clinical cohort was used as a validation set. Results During a median follow-up of 150 weeks, 19 patients (25.7%) relapsed. Glucocorticoid dose, tapering speed, and concomitant immunosuppressive use did not differ between relapse and non-relapse groups. The numbers of Tph2 cells were higher (median 1.8 vs 0.9 cells/μL, P=0.018) and CD19+ B cells were lower (median 82 vs 133 cells/µL, P=0.002) in the relapse group compared with the non-relapse group at baseline. Multivariable analysis identified Tph2 cells and CD19+ B cells as the independent predictors of relapse. This peripheral immune profile was mirrored in affected tissues, where CX3CR1+ Tph2-like cells accumulated in extrafollicular regions of lacrimal glands with relatively low B-cell infiltration (T-B-pathotype). In lacrimal gland biopsies, T-B-pathotype was associated with a higher relapse rate (P=0.022), findings reproduced in an independent validation set. Conclusion Higher Tph2 cells and lower CD19+ B cells in blood and T-B-pathotype in lacrimal glands are potentially associated with increased relapse risk in IgG4-RD.
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Authors Kanako Shimanuki, Mitsuhiro Akiyama, Koichi Saito, Waleed Alshehri, Takeru Maruyama, Takanori Sasaki, Keiko Yoshimoto, Noriyasu Seki, Hideto Tsujimoto, Kenji Chiba, Yuko Kaneko
Journal Lara D. Veeken
Year 2026
DOI
10.1093/rheumatology/keag417
URL
https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/keag417/70622216/keag417.pdf
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