Primary Biliary Cirrhosis Associated with HLA, IL12A, and IL12RB2 Variants

• Published in: The New England journal of medicine Vol. 360; no. 24; pp. 2544 - 2555
• Main Authors: Hirschfield, Gideon M, Liu, Xiangdong, Xu, Chun, Lu, Yan, Lu, Yue, Xie, Gang, Gu, Xiangjun, Walker, Erin J, Jing, Kaiyan, Juran, Brian D, Mason, Andrew L, Myers, Robert P, Peltekian, Kevork M, Ghent, Cameron N, Coltescu, Catalina, Atkinson, Elizabeth J, Heathcote, E. Jenny, Lazaridis, Konstantinos N, Amos, Christopher I, Siminovitch, Katherine A
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 11.06.2009
• Subjects: Autoimmune diseases; Biological and medical sciences; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Genes, MHC Class II; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; HLA Antigens - genetics; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; Humans; Interleukin-12 Receptor beta 2 Subunit - genetics; Interleukin-12 Subunit p35 - genetics; Interleukin-23 - genetics; Liver cirrhosis; Liver Cirrhosis, Biliary - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lymphocytes; Medical sciences; Other diseases. Semiology; Polymorphism, Single Nucleotide; Quality control; Receptors, Interleukin-12 - genetics; Transplants & implants; Canada; North America; Medicine; Variant; Primary biliary cirrhosis; HLA-System; Association; Genetic variability; Major histocompatibility system; Digestive diseases; Hepatic disease; Genotype; Class I histocompatibility antigen
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0810440

A genomewide association analysis of patients with primary biliary cirrhosis suggests that variation in interleukin-12 signaling may confer a risk of disease. This study also firmly implicates variants at the HLA locus as a risk factor. A genomewide association analysis of patients with primary biliary cirrhosis suggests that variation in interleukin-12 signaling may confer a risk of disease. This study also firmly implicates variants at the HLA locus as a risk factor. Primary biliary cirrhosis is the most common autoimmune liver disease, affecting up to 1 in 1000 women over 40 years of age. 1 Treatment for this chronic cholestatic condition remains empirical. 2 The granulomatous destruction of interlobular bile ducts that characterizes primary biliary cirrhosis is almost always associated with antimitochondrial antibodies specific for the E2 subunit of the pyruvate dehydrogenase complex. 3 The hepatic accumulation of autoreactive T lymphocytes in patients with primary biliary cirrhosis, as well as data from animal models of autoimmune cholangitis, implicate T lymphocytes — CD4+ T helper lymphocytes in particular — in the pathogenesis of primary biliary cirrhosis. . . .