Decreased serum leptin levels in primary biliary cirrhosis: a link between metabolism and autoimmunity?

Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology resulting in the progressive destruction of the intrahepatic bile ducts and leading to chronic cholestasis and ultimately liver cirrhosis and failure. The immune response in PBC seems to be mediated by autoantibodies as well as autoreactive T lymphocytes directed against mitochondrial antigens in biliary epithelial cells, primarily PDC-E2. Experimental evidence suggests a role of the hormone/cytokine leptin in autoimmune diseases. Leptin is an adipocyte-derived molecule that acts as a hormone influencing food intake and energy metabolism as well as a cytokine with pro-inflammatory, immune-regulatory functions. To study serum leptin in PBC and its association with disease severity, we evaluated serum levels in 37 patients with PBC (27 with no signs of fibrosis or cirrhosis at histologic examination) and 37 age- and sex-matched healthy controls using a validated ELISA method. We found that patients with PBC had significantly lower leptin serum levels compared with healthy controls (13.6 +/- 13.8 vs. 17.6 +/- 11.6; P < 0.05). No correlation between disease severity and serum leptin levels was found. This study has demonstrated that leptin levels are decreased in the serum of patients with PBC but do not seem to be associated with disease severity. Data do not seem to indicate a direct role of leptin in the perpetuation of the autoimmune response in PBC. However, further studies are warranted to further characterize the functions of leptin during the natural history of autoimmunity.