Review of a novel disease entity, immunoglobulin G4-related disease

Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.

Review of a novel disease entity, immunoglobulin G4-related disease

Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.

Review of a novel disease entity, immunoglobulin G4-related disease

Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.

Effects of Bulb Type Palatal Lift Prosthesis Therapy on Nasality and Velopharyngeal Function of Patients Following Palatoplasty / Oral Science International

In the present study, the effects of bulb type palatal lift prosthesis (bulb-PLP) therapy on nasality and velopharyngeal function (VPF) of patients with velopharyngeal incompetence (VPI) following palatoplasty were longitudinally assessed.The subjects included 18 patients (3 to 52 years of age) who had shown persistent VPI following palatoplasty and who had received bulb-PLP therapy. Nasality and VPF were assessed by perceptual voice analysis, nasometer test, blowing test, and cephalometric radiographic examination. Based on the outcomes of bulb-PLP therapy, the subjects were classified into two groups: the effective group and the ineffective group. Furthermore, the obturating and VPF-activating effects by bulb-PLP therapy were analyzed, and factors relating to different VPF activities were determined.All subjects achieved adequate VPF by wearing a bulb-PLP. After treatment, 10 patients (55.6%) achieved successful activation of VPF without bulb-PLP (the effective group), while persistent VPI remained in 8 patients (the ineffective group). The beginning-blowing ratio of the effective group was significantly greater than that of the ineffective group (P < 0.05) and the velopharyngeal distance (V-P distance) of the effective group tended to be smaller (P = 0.07). Regarding the shape of the bulb head, the angular type was dominant in the ineffective group, while the round type was dominant in the effective group.Bulb-PLP therapy was useful for providing adequate VPF activation. Possible signs of the subsequent effective activation of VPF are considered to be: 1) preexisting adequate VPF on blowing, 2) smaller V-P distance, and 3) synchronized palatopharyngeal movement.

An Anti-apoptotic Role of NF-κB in TNFα-induced Apoptosis in an Ameloblastoma Cell Line / Oral Science International

Nuclear factor-κB (NF-κB) is involved in the promotion of cell survival in a variety of cell types. The present study focused on the role of NF-κB in TNFα-induced apoptosis in an ameloblastoma. Immunohistochemical staining revealed p65 NF-κB protein to be expressed in ameloblastoma tissues. Furthermore, immunoblotting and immunocytochemistry analyses showed that the stimulation of TNFα in an ameloblastoma cell line (AM-1) induced p65 NF-κB translocation from the cytoplasm to the nucleus, indicating NF-κB activation. These findings were confirmed by an NF-κB luciferase reporter assay, which detected enhanced NF-κB transcription activity of AM-1 cells by TNFα stimulation. Moreover, pretreatment with SN50, a nuclear translocation inhibitor, prior to TNFα stimulation, effectively inhibited TNFα-induced NF-κB activation in AM-1 cells. In order to reveal the role of NF-κB activation during TNFα-induced apoptosis in AM-1 cells, an apoptosis assay was performed, and showed that the potential of TNFα in inducing apoptosis in AM-1 cells was significantly elevated by inhibiting the NF-κB activation. These results suggest that NF-κB plays an anti-apoptotic role in TNFα-induced apoptosis in AM-1 cells.