ArticleRheumatology (Oxford, England)2026
Association of Th2-like inflammation with Tfh/Tph-germinal center immune programmes in submandibular gland lesions of IgG4-related disease.
Article in Rheumatology (Oxford, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesIgG4-related disease (IgG4-RD) has long been associated with Th2-predominant immune responses and allergic features. However, the immunological context underlying lesional Th2-like inflammation remains incompletely understood.
methodsBulk RNA-seq data from 49 submandibular gland lesions of IgG4-RD were analyzed. Module scores representing Th2, Tfh/Tph, B cell, germinal center B cell (GC_B), plasma cell, macrophage and stromal/fibrotic programmes were calculated. Correlations between Th2 module scores and other immune/stromal modules were assessed using Spearman correlation analysis. Differentially expressed genes between Th2-high and Th2-low lesions were also evaluated.
resultsTh2 module scores were strongly associated with Tfh, Tfh/Tph and Tph helper T cell programmes, as well as with B cell, GC_B and plasma cell signatures. In addition, Th2 module scores positively correlated with M2 macrophage and fibrosis-associated macrophage (FAM) programmes. Differential expression analysis demonstrated increased expression of chronic helper T cell-related genes, including PDCD1, TOX and MAF, together with plasmablast-associated genes such as JCHAIN, MZB1 and PRDM1 in Th2-high lesions. In contrast, serum IgG4 and IgE levels did not significantly differ between Th2-high and Th2-low groups.
conclusionsLesional Th2-like inflammation in IgG4-RD was closely associated with chronic Tfh/Tph-germinal center immune programmes linked to plasmablast and M2/FAM macrophage responses. No clear association with available systemic allergy-related parameters was observed in this cohort.
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