Polymorphism in Macrophage Migration Inhibitory Factor -173GC in Pediatric Patients with Autoimmune Hepatitis

Abstract

Purpose: Autoimmune hepatitis (AIH) is a chronic disease that may lead to cirrhosis. The immunopathogenesis of AIH is not fully understood and it mainly involves T-cell mediated mechanism. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that promotes T cell response and its polymorphism may serve as a severity marker of AIH. No previous study has considered investigating MIF polymorphism in children with AIH.

Methods: Forty-two children with definite diagnosis of AIH were enrolled along with 100 age and sex matched controls. All participants were tested for polymorphism at -173GC (rs755622) of MIF gene. All patients received the standard protocol of steroid plus azathioprine to achieve remission. Liver biopsy was performed at time of diagnosis for all patients and only 18 of them underwent a second biopsy after treatment.

Results: No statistically significant differences in the frequency of the genotypes GG and GC or in allele distribution were found in both patient and control groups (p=0.590, 0.640 respectively). Initial alanine aminotransferase (ALT) levels at the time of presentation was significantly higher in the GC group than GG group (p=0.020). GC genotype significantly correlated with disease relapse (r=0.41, p=0.007). Regression of necroinflammation and the fibrosis score in the second liver biopsy was statistically significant in the GG group (p<0.0001, p=0.010 respectively).

Conclusion: MIF -173GC polymorphism is associated with clinically significant markers of pediatric AIH, including increased initial serum ALT levels, may help predict necroinflammatory/fibrosis regression effectively, following immunosuppressive treatment.

Keywords: Autoimmune hepatitis; Children; Macrophage migration inhibitory factor; −173 GC polymorphism.

Fig. 1. Gel electrophoresis of polymerase chain reaction product. Lane 1 contains 50 bp DNA ladder. Lanes 4, 5, 6, 7, and 10 contain two bands of 268 and 97 bp that are indicators of GG genotype, lanes 2, 3, 8, and 9 contain four bands (268, 206, 97, and 62 bp) that represent GC genotype, while 3 bands (206, 97, and 62 bp) of CC genotype are absent.

Fig. 2. Error bar representing the mean steroid dose in different genotypic patient groups.

CI: confidence interval.