Elsevier

Journal of Autoimmunity

Volume 25, Issue 2, September 2005, Pages 133-140
Journal of Autoimmunity

cDNA microarray analysis of autoimmune hepatitis, primary biliary cirrhosis and consecutive disease manifestation

https://doi.org/10.1016/j.jaut.2005.03.009Get rights and content

Abstract

While autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) usually have distinct clinical manifestations, some patients present with features of both conditions. Using cDNA microarrays, we analyzed and compared gene expression profiles in 8 patients with AIH, 9 with PBC, 8 with chronic hepatitis C (CHC), 8 with non-alcoholic steatohepatitis (NASH) and 9 with normal livers. We subsequently applied this method to a tissue sample from a 61-year-old woman with overlapping features of both AIH and PBC. A 61-year-old woman was admitted to our hospital for evaluation of elevated serum alkaline phosphatase. A liver biopsy showed accumulation of mononuclear cells around the bile duct cells, a feature characteristic of chronic non-suppurative destructive cholangitis (CNSDC). Three years later, her serum alanine aminotransferase (ALT) level had increased, and a liver biopsy demonstrated evidence of a severe form of hepatitis. A cDNA microarray analysis of both biopsies identified the molecular events associated with her altered histology. The expression profile of this patient, which was originally different from that of the other PBC patients, changed to an AIH pattern. Our results suggest that this patient has characteristics of both AIH and PBC.

Section snippets

Patients and tissue samples

Liver biopsies were obtained from 9 patients with normal liver, 8 with AIH, 9 with PBC, 8 with chronic hepatitis C (CHC) and 8 with non-alcoholic steatohepatitis (NASH), all of whom had been admitted to Kanazawa University Hospital between 1997 and 2002 (Table 1). Biopsy samples were immediately frozen and stored in liquid nitrogen until use.

Tissue samples were assessed histologically by standard methods [11], [12] (Table 2). AIH was diagnosed according to the criteria of the International

Hierarchical clustering of AIH and PBC patients

To compare the expression profiles in AIH and PBC, we performed hierarchical clustering of all 1080 genes in liver biopsies of 8 AIH and 9 PBC patients, all of whom had been selected because they did not have advanced liver disease (Table 1). The patients were clustered into two groups, one for AIH and the other for PBC, with a few exceptions (Fig. 1a, p < 0.05). Interestingly, 1 of the AIH patients was clustered into the PBC group, while 2 PBC patients were clustered into the AIH group.

Gene expression differentiating AIH from PBC

We

Discussion

Despite extensive cytokine profiling of the liver, the pathogenesis of AIH and PBC has not been completely elucidated. Moreover, diagnosis of these diseases is sometimes difficult, since some patients present with features of both. We have applied cDNA microarray analysis to patients with AIH and PBC to determine the expression profiling of these diseases.

Hierarchical clustering of all 1080 analyzed genes demonstrated differences in gene expression patterns between AIH and PBC (Fig. 1a, p < 

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