Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells
2003 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 88, no 4, 1445-1452 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2003. Vol. 88, no 4, 1445-1452 p.
Adult, Antibody Specificity, Autoantibodies/blood, Autoantigens/*immunology, Binding; Competitive, Biopsy, Cell Line, Enterochromaffin-like Cells/*enzymology/immunology, Female, Gastric Mucosa/immunology, Gene Expression, Histidine Decarboxylase/genetics/*immunology, Humans, Immunoblotting, Immunohistochemistry, Immunosorbent Techniques, Mast Cells/enzymology, Parietal Cells; Gastric/immunology, Polyendocrinopathies; Autoimmune/*immunology, Pyridoxal Phosphate/*pharmacology, Research Support; Non-U.S. Gov't
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-72171DOI: 10.1210/jc.2002-021761PubMedID: 12679420OAI: oai:DiVA.org:uu-72171DiVA: diva2:100082