High-throughput RNA sequencing reveals distinct gene signatures in active IgG4-related disease

Abstract

We aimed to characterize the molecular differences and effects from prednisone treatment among IgG4-related disease with salivary gland lesions (RD-SG), without SG lesions (RD-nonSG), and IgG4-related retroperitoneal fibrosis (RF). RNA sequencing was conducted on blood from 25 RD-SG, 11 RD-nonSG, 3 RF and 10 control subjects. Among these, 8 RD-nonSG and 12 RD-SG patients were subjected to treatment with prednisone and/or glucocorticoid-sparing agents. Six RD patients had a longitudinal time point. The mRNA levels of IgG4 and IgE, genes specific for Th2 cells, eosinophils, and neutrophils were over-expressed in RD-SG and RD-nonSG. A B-cell signature was suppressed in patients group versus controls, while Th1, Th2, Treg, and eosinophil gene signatures were increased in patients without treatment. Interestingly, Tfh genes and B cell signature were decreased at flare disease state. Prednisone treatment led to increased neutrophil, but decreased Treg signatures. Serum IgG4 levels correlated with the eosinophil and neutrophil gene signatures in RD-SG patients, and with a B cell signature in only RD-nonSG patients. IgG4, IgE, and cell-specific signatures are regulated in patients, suggesting the imbalance of immune and inflammatory cells in IgG4-related disease. Prednisone treatment selectively modulates Treg, eosinophil, and neutrophil signatures.

Identifying clinical subgroups in IgG4-related disease patients using cluster analysis and IgG4-RD composite score

“…It may be caused by individual treatment, as data collected from a real world study are different in terms of the follow-up time and other confounding factors. Finally, some variables with a potential role in the pathogenesis of IgG4-RD were not investigated, such as ANA, RF, and neutrophils [26,[47][48][49][50][51].…”

Esophageal IgG4 levels correlate with histopathologic and transcriptomic features in eosinophilic esophagitis

“…Currently, EoE is not considered to be on the spectrum of IgG4-RD; however, IgG4-RD may serve as a paradigm to investigate the biological basis of IgG4 and its involvement in EoE. For example, transcriptomic analysis in patients with IgG4-RD revealed differences in mRNA levels of IgG4 among patients with different clinical manifestations of IgG4-RD, and differences in immune and inflammatory cell gene signatures correlated with disease activity (48).…”

Multiple Processes May Involve in the IgG4-RD Pathogenesis: An Integrative Study via Proteomic and Transcriptomic Analysis

“…These data showed how elevated levels of such cytokines and chemokines can induce IgG4 plasma cell infiltration, high IgG4 levels in the periphery, and impact tissue fibrosis in the LSG of IgG4-RD patients ( 13 ). Further, researchers using high-throughput RNA sequencing technology revealed the molecular differences and effects from prednisone treatment among IgG4-related disease with salivary gland lesions (RD-SG), without SG lesions (RD-nonSG), and IgG4-related retroperitoneal fibrosis (RF) ( 14 ). However, the molecular mechanisms and appropriate therapeutic strategies underlying the pathogenesis of IgG4-RD are still unclear.…”