PANCREAS

Serum antibodies to carbonic anhydrase IV in patients with autoimmune pancreatitis

I Nishimori¹, E Miyaji¹, K Morimoto¹, K Nagao², M Kamada², S Onishi¹

¹ Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi, Japan
² Pharmaceutical Frontier Research Laboratories, Japan Tobacco Inc., Yokohama, Kanagawa, Japan

Correspondence to:
Correspondence to:
Dr I Nishimori
Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan; nisao{at}med.kochi-u.ac.jp

Background and aims: Serum antibodies to carbonic anhydrase (CA) II have been reported in patients with autoimmune pancreatitis (AIP) and Sjögren’s syndrome (SjS). However, their significance in the pathogenesis of these diseases is controversial. The aim of this study was to identify serum antibodies to CA isozymes, which are expressed in ductal cells of the pancreas.

Methods: Recombinant proteins of human CAs IV, IX, and XII were obtained using a bacterial expression system, and five CA IV peptides with theoretically high antigenicity were synthesised. Western blotting and enzyme linked immunosorbent assay (ELISA) were used to detect serum antibodies to the CA isozymes.

Results: The first screening analysis by western blot showed serum antibodies to CA IV among three CA isozymes in patients with idiopathic chronic pancreatitis, including AIP patients. Further analysis by ELISA showed a significantly increased prevalence of serum antibodies to the truncated CA IV protein and the CA IV synthetic peptide (LGS LTT PTC DEK VVW TVF REP I) in patients with definite AIP (4/15 and 6/20, respectively; p<0.01), probable AIP (6/14 and 3/14; p<0.02), and SjS (9/20 and 8/40; p<0.001) compared with normal controls (0/26). There was no significant difference in the antibody prevalence rates between normal controls and patients with alcoholic chronic pancreatitis (2/15 in each) or pancreatic cancer (2/14 and 1/14, respectively). The presence of serum antibodies to the CA IV peptide showed significant correlations with serum gamma-globulin and IgG levels in AIP patients.

Conclusions: These findings suggest that CA IV may be a target antigen that is commonly expressed in epithelial cells of specific tissues involved in AIP and its related diseases.

Abbreviations: AIP, autoimmune pancreatitis; ANA, antinuclear antibody; CA, carbonic anhydrase; GPI, glycosyl phosphatidylinositol; GST, glutathione S-transferase; ICP, idiopathic chronic pancreatitis; PCR, reverse transcription-polymerase chain reaction; SjS, Sjögren’s syndrome; ELISA, enzyme linked immunosorbent assay

Keywords: autoimmune pancreatitis; autoimmune epithelitis; carbonic anhydrase IV; serum antibody; Sjögren’s syndrome

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