The immunobiology of primary sclerosing cholangitis

Jonathan H. Aron, Christopher Bowlus

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease histologically characterized by the presence of intrahepatic and/or extrahepatic biliary duct concentric, obliterative fibrosis, eventually leading to cirrhosis. Approximately 75% of patients with PSC have inflammatory bowel disease. The male predominance of PSC, the lack of a defined, pathogenic autoantigen, and the potential role of the innate immune system suggest that it may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC is associated with several classic autoimmune diseases, and the strongest genetic link to PSC identified to date is with the human leukocyte antigen DRB0103 haplotype. The precise immunopathogenesis of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Currently, there is no effective therapy for PSC and developing a rational therapeutic strategy demands a better understanding of the disease.

Original languageEnglish (US)
Pages (from-to)383-397
Number of pages15
JournalSeminars in Immunopathology
Volume31
Issue number3
DOIs
StatePublished - Sep 2009

Fingerprint

Sclerosing Cholangitis
Autoimmune Diseases
Immune System
Fibrosis
Cholangitis
Autoantigens
HLA Antigens
Portal Vein
Bile Ducts
Inflammatory Bowel Diseases
Chemokines
Bile
Haplotypes
Liver Diseases
Immunity
Pathologic Constriction
Lymphocytes
Cytokines
Inflammation
Liver

Keywords

  • Biliary cirrhosis
  • Inflammatory bowel disease
  • Pathogenesis
  • Primary sclerosing cholangitis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

The immunobiology of primary sclerosing cholangitis. / Aron, Jonathan H.; Bowlus, Christopher.

In: Seminars in Immunopathology, Vol. 31, No. 3, 09.2009, p. 383-397.

Research output: Contribution to journalArticle

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