title: Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells.
abstract: Patients with autoimmune polyendocrine syndrome type 1 often have autoantibodies against neurotransmitter synthesizing enzymes, including the pyridoxal phosphate-dependent enzymes glutamic acid decarboxylase and aromatic L-amino acid decarboxylase. Using a candidate approach, we have identified the histamine-synthesizing enzyme histidine decarboxylase, also pyridoxal phosphate dependent, as an autoantigen in this disorder. Anti-histidine decarboxylase antibodies reacting with in vitro translated antigen were found in 36/97 (37%) of autoimmune polyendocrine syndrome type 1 patients studied. The antibodies also reacted with the native enzyme in HMC-1 cell lysates and did not cross-react with the highly homologous aromatic L-amino acid decarboxylase. Anti-histidine decarboxylase antibodies were associated with a history of intestinal dysfunction (P = 0.017). Gastric and duodenal biopsies from a patient with anti-histidine decarboxylase antibodies were studied by immunohistochemistry. The oxyntic mucosa was found to lack the histamine producing enterochromaffin-like cells, suggestive of an autoimmune destruction. To our knowledge, this is the first report of autoantibodies against histidine decarboxylase and absence of gastric enterochromaffin-like cells.
authors.affiliation: Department of Medical Sciences, Uppsala University, University Hospital, 751 85 Uppsala, Sweden. Filip.Skoldberg@medsci.uu.se
authors.forename: Filip
authors.initials: F
authors.lastname: Sköldberg
authors.forename: Guida M
authors.initials: GM
authors.lastname: Portela-Gomes
authors.forename: Lars
authors.initials: L
authors.lastname: Grimelius
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nilsson
authors.forename: Jaakko
authors.initials: J
authors.lastname: Perheentupa
authors.forename: Corrado
authors.initials: C
authors.lastname: Betterle
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
authors.forename: Jan
authors.initials: J
authors.lastname: Gustafsson
authors.forename: Anders
authors.initials: A
authors.lastname: Rönnblom
authors.forename: Fredrik
authors.initials: F
authors.lastname: Rorsman
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
mesh_terms: D000328:Adult; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D001667:Binding, Competitive; D001706:Biopsy; D002460:Cell Line; D019861:Enterochromaffin-like Cells / Q000201:enzymology* / Q000276:immunology; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology; D015870:Gene Expression; D006640:Histidine Decarboxylase / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007163:Immunosorbent Techniques; D008407:Mast Cells / Q000201:enzymology; D010295:Parietal Cells, Gastric / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D011732:Pyridoxal Phosphate; D006640:Histidine Decarboxylase