Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry?
Autoimmune pancreatitis is a recently defined nosological entity, which accounts for 4.6-6% of all forms of chronic pancreatitis and is often associated with other autoimmune diseases, particularly Sjogren's syndrome. Possession of the HLA DRB1*0405-DQB1*0401 genotype confers a risk for the development of autoimmune pancreatitis. Autoantibodies against carbonic anhydrase II and lactoferrin are frequently present in affected subjects and are suspected to have a pathogenic role. A link between gastric infection by Helicobacter pylori and autoimmune pancreatitis has been hypothesized. We used in silico protein analysis and search for HLA binding motifs to verify this hypothesis. We found a significant homology between human carbonic anhydrase II and alpha-carbonic anhydrase of Helicobacter pylori, an enzyme which is fundamental for the survival and proliferation of the bacterium in the gastric environment. Moreover, the homologous segments contain the binding motif of the HLA molecule DRB1*0405. Our data strengthen the hypothesis that gastric Helicobacter pylori infection can trigger autoimmune pancreatitis in genetically predisposed subjects.
Guarneri
F
F
Istituto di Dermatologia, Policlinico Gaetano Martino, Università di Messina, Messina, Italy. f.guarneri@tiscali.it
Guarneri
C
C
Benvenga
S
S
D000596:Amino Acids / Q000032:analysis; D001327:Autoimmune Diseases / Q000382:microbiology; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000737:chemistry; D059811:HLA-DRB1 Chains; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori; D006801:Humans; D008958:Models, Molecular; D010195:Pancreatitis / Q000276:immunology / Q000382:microbiology*; D011487:Protein Conformation
D000596:Amino Acids; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D002256:Carbonic Anhydrases