A Macrophage Migration Inhibitory Factor Polymorphism Is Associated with Autoimmune Hepatitis Severity in US and Japanese Patients.

ABSTRACT

BACKGROUND: The pathogenesis of autoimmune hepatitis (AIH) is incompletely understood. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine implicated in the pathophysiology of multiple autoimmune diseases. We recently reported that MIF expression was increased in a US AIH cohort. MIF expression in non-Western AIH patients is unknown. A MIF-173 GC single nucleotide polymorphism in the MIF promoter (rs755622) is clinically associated with steroid resistance in several inflammatory disorders but has not been evaluated in AIH. AIM: To compare MIF polymorphisms and their relationship to clinical parameters in AIH patients from the USA and Japan. METHODS: DNA and matched sera from AIH patients and healthy controls from Japan (N = 52) were compared to the US group. Serum concentrations of MIF and its circulating receptor CD74 were measured by ELISA. MIF-173 GC (rs755622) and MIF-794 CATT5-8 (rs5844572) polymorphisms were analyzed by standard methods. MIF genotypes were correlated with serum ALT and steroid requirements. RESULTS: Serum MIF was increased in Japanese AIH patients versus local controls, in agreement with the US AIH patients. Within both AIH groups, ALT was higher in CC/GC versus GG patients. Further, the steroid requirement was higher in AIH patients with GC/CC genotypes from both groups. In the Japanese patient group, the GC/CC genotype also was associated with acute symptomatic presentation. CONCLUSIONS: The MIF-173 CC/GC genotypes may be associated with both higher ALT and maintenance steroid requirements in AIH patients from the USA and Japan. This polymorphism could be a marker of disease severity in AIH patients.