IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in
cancer patients and in patients with
IgG4-related diseases.
Extrahepatic cholangiocarcinomas including
gall bladder cancer are often accompanied by significant
IgG4 reactions; these reactions show a negative correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of immune surveillance is associated with cytotoxic T cells. The regulatory
cytokine IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell switching to
IgG4 in the presence of
IL-4.
Cholangiocarcinoma cells may function as nonprofessional antigen presenting cells that indirectly induce
IgG4 reactions via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10-producing cells that directly induce
IgG4 reactions. Moreover,
IgG4-related disease is a high-risk factor for
cancer development; IgG4-related
sclerosing cholangitis (IgG4-SC) cases associated with
cholangiocarcinoma or its precursor lesion biliary intraepithelial
neoplasia (
BilIN) have been reported. IgG4-positive cell infiltration is an important finding of IgG4-SC but is not a histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its differentiation from
cholangiocarcinoma remains important.