Elevated immunoglobulin G4 level is associated with reduced colectomy-free survival in patients with primary sclerosing cholangitis and ulcerative colitis.
ABSTRACT BACKGROUND AND AIM: Patients with primary sclerosing cholangitis (PSC) and elevated immunoglobulin (Ig) G4 have been shown to have more severe disease with a shorter time to orthotopic liver transplantation (OLT). The aim of the study was to investigate the clinical outcomes of PSC and UC in patients with elevated serum IgG4. METHODS: We analyzed data from 50 patients with PSC and known serum levels of IgG4. They were divided into groups called high IgG4 (>112IU/L; n=10) or normal IgG4 (n=40). We compared the requirement of OLT and colectomy between groups. RESULTS: High IgG4 was found in 10 PSC patients (20%). UC was associated in 9/10 patients with high IgG4 vs. 32/40 patients with normal IgG4 (p=0.67). Patients with high IgG4 were younger at PSC diagnosis (28.1±13.9 vs. 37.6±13.4years, P=0.04), more likely to have backwash ileitis (7/9 vs. 12/32, P<0.001) and UC flares (median of 5.5 vs. 1.5, P=0.02). Kaplan-Meier curve analysis showed that patients with elevated IgG4 had reduced colectomy-free survival than patients with normal IgG4 (Log Rank p<0.001). The median time to colectomy was 5years from UC diagnosis in high IgG4 group vs. 12years in the normal IgG4 group (p=0.01). CONCLUSIONS: Elevated IgG4 was seen in a small number of PSC patients. Most of these patients had associated UC, were younger at the time of PSC diagnosis, more likely to have backwash ileitis and had reduced colectomy-free survival than patients with normal IgG4.
- SourceAvailable from: Palak Jitendrakumar Trivedi[show abstract] [hide abstract]
ABSTRACT: Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) all nestle within the umbrella term of autoimmune liver disease, in which the end result is immune-mediated hepatocellular or hepatobiliary injury. All three conditions are associated with gut inflammation; PSC and AIH being strongly linked to inflammatory bowel disease (IBD) and PBC to coeliac disease. This clinical observation has stimulated several intriguing pathogenic concepts in which gut commensals, pathogens and intestinal antigens are all implicated in causing liver injury. Th17-cells have also been linked to AIH, PBC and more recently PSC. Given that the intestine is a key regulator of immunopathogenic Th17 responses, this may underpin a common disease mechanism and open up novel treatment avenues based on rational targeting of immune pathways. Moreover, the discovery of long-lived mucosal memory T-cells being recruited to the liver in response to aberrantly expressed endothelial-cell adhesion molecules and chemokines, which are normally 'gut-restricted,' could plausibly explain why these diseases are associated with site-restricted tissue distributions and pave the way for therapeutic strategies based on modulating tissue specific lymphocyte homing. That particular gene-polymorphisms have been found which confer combined PSC/IBD susceptibility underscores the fundamental role of mucosal immunogenicity in disease pathogenesis. Mucosal lymphocytes may also play a pivotal role in graft versus host disease affecting the liver, and there is increasing evidence to support dysregulated mucosal immunity as being responsible for the hepatic manifestations of gluten-sensitive enteropathy, graft versus host disease, as wells as the pancreatobiliary manifestations of IgG4-related disease.Journal of Autoimmunity 07/2013; · 8.15 Impact Factor