Analysis of Innate and Adaptive Immunological Characteristics in Patients with IgG4-Related Disease

Abstract

Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic immunological disorder characterized by fibroinflammatory conditions; however, the pathobiology of IgG4-RD has not been fully identified. Objective: This study aimed to analyze systemic differences of innate and adaptive immune cells from healthy controls and patients with IgG4-RD. Methods: Healthy controls (n = 9) and IgG4-RD patients (n = 7) were recruited with informed consent. Peripheral blood was collected from healthy controls and IgG4-RD patients, and three blood samples from IgG4-RD patients were recollected two months after the last rituximab (RTX) treatment. The various immune cells and cytokine productions were measured by flow cytometry. Results: Blood CD14 + monocytes and steady-state follicular helper T cells were increased in patients with IgG4-RD. However, there were no changes in other immune cell populations, including B cells, CD4 T cells, CD8 T cells, and innate lymphoid cells. Also, the TGF-β-producing CD14 + monocytes were significantly augmented in patients with IgG4-RD. Two months after RTX treatment, total B cells (CD19 +) were depleted; however, the expressions of TGF-β from CD14 + monocytes remained unchanged. Conclusion: These findings showed that IgG4-RD is related to the increment of CD14 + monocytes. Besides, controlling increased TGF-β-producing CD14 + monocytes with RTX treatment might be a conducive way to regulate IgG4-RD.

Single-cell transcriptome analysis and protein profiling reveal broad immune system activation in IgG4-related disease

“…These subsets include CD14 + monocytes (MNs) (LYZ + CD14 + ), CD16 + MNs (LYZ + FCGR3A + ), DCs (CD1C + ), CD4 + T cells (CD4 + ), CD8 + T cells (CD8A + ), proliferating lymphocytes (MKI67 + ), natural killer (NK) cells (KLRF1 + ), B cells (CD19 + ), and platelets (PPBP + ) (Figure 1E). Of note, the percentages of B cells and CD4 + T cells tended to be lower in IgG4-RD patients than in HCs, while CD14 + MNs showed an opposite trend (Figure 1, F and G), which was also demonstrated in a recent study (14).…”

T Cell Roles and Activity in Chronic Sclerosing Sialadenitis as IgG4-Related Disease: Current Concepts in Immunopathogenesis

“…(2) CD4 + + Tfh in IgG4-RD . Generally, in IgG4-RD, these cells are significantly increased in both peripheral blood and disease-affected organs [ 6 , 9 , 29 , 60 , 66 , 67 , 70 ].…”

“…Grados et al showed that CD4 + CXCR5 + PD1 + Tfh cells were normalized under RTX treatment [ 71 ]. However, Sohan et al revealed that, after RTX treatment, Tfh cells and TGF- β -producing cells remained in the blood of IgG4-RD patients, suggesting that these cells might be risk factors for incomplete resolution of the inflammatory process [ 9 ].…”