Pathogenicity of IgG in patients with IgG4-related disease

Abstract

IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice.

Emerging Treatment Models in Rheumatology: IgG4‐Related Disease: Insights Into Human Immunology and Targeted Therapies

“…21 The passive transfer model of purified human IgG to neonatal mice also suggests autoreactivity. 35 These observations remain the most compelling evidence that IgG4-RD might be driven by self-antigen. However, given the established association of CD4 + CTLs with chronic viral infections and the highly-restricted repertoire of these cells, the possibility that the disease arises from chronic viral antigen stimulation has not been excluded.…”

“…35 Purified IgG subclass molecules from the serum of patients with IgG4-RD and controls were transferred to neonatal mice. 35 This transfer induced pathologic changes in both the pancreas and submandibular glands, two organs commonly affected by IgG4-RD in humans.…”

“…35 Purified IgG subclass molecules from the serum of patients with IgG4-RD and controls were transferred to neonatal mice. 35 This transfer induced pathologic changes in both the pancreas and submandibular glands, two organs commonly affected by IgG4-RD in humans. Although transfer of either purified IgG1 or IgG4 alone produced the disease phenotype, the transfer of both molecules together led to reduced IgG1 deposition and a decrease in the histopathologic severity of disease within affected organs.…”

“…Although transfer of either purified IgG1 or IgG4 alone produced the disease phenotype, the transfer of both molecules together led to reduced IgG1 deposition and a decrease in the histopathologic severity of disease within affected organs. 35 …”

Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease

“…It is possible that IgG4 may undergo altered glycosylation in disease and may acquire the ability to bind activating Fc receptors. IgG4-containing immune complexes could also potentially recruit mannose-binding lectin and thus activate complement [10]. In a recent study by Shiokawa et al, purified human IgG1 and IgG4 from IgG4-RD subjects was found to induce pancreatic lesions in infant mice [10].…”