Possible involvement of T helper type 2 responses to Toll-like receptor ligands in IgG4-related sclerosing disease

• Published in: Gut Vol. 59; no. 4; pp. 542 - 545
• Main Authors: Akitake, Reiko, Watanabe, Tomohiro, Zaima, Chikage, Uza, Norimitsu, Ida, Hiroshi, Tada, Shinsuke, Nishida, Naoshi, Chiba, Tsutomu
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group 01.04.2010; BMJ Publishing Group LTD
• Subjects: Aged; Antigens; Autoimmune Diseases - immunology; Bile; Biological and medical sciences; Biopsy; Cells, Cultured; Cholangitis, Sclerosing - immunology; Colon; Cytokines; Disease; Endoscopy; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunoglobulin G - metabolism; Immunology; Ligands; Lymphatic system; Lymphocytes; Male; Medical sciences; Pancreas; Pancreatitis - immunology; Patients; Th2 Cells - immunology; Toll-Like Receptors; Toll like receptor; Th2 lymphocyte; Ligand; Gastroenterology
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gut.2009.200972

We report a case of immunoglobulin G4 (IgG4)-related sclerosing disease involving the pancreas, liver and salivary glands. Massive infiltration of IgG4-expressing plasma cells was seen in the liver and submandibular lymph nodes. Interestingly, accumulation of IgG4-expressing plasma cells was also seen in the colon and terminal ileum. Peripheral blood mononuclear cells (PBMCs) isolated from this patient exhibited enhanced production of IgG4 and interleukin-10 upon stimulation with Toll-like receptor (TLR) ligands as compared with those from a healthy control. In contrast, production of tumour necrosis factor α and interferon γ by PBMCs from this patient was markedly reduced. Since colonic mucosa is always exposed to TLR ligands derived from commensal organisms, the results of immunological studies suggest that enhanced T helper type 2 responses to intestinal microflora may underlie the immunopathogenesis in this patient with IgG4-related sclerosing disease.