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Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Autoimmuna sjukdomar (Kämpe))
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. (Endokrin patologi)
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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
Abstract [en]

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.
Keyword [en]
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
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-72171DOI: 10.1210/jc.2002-021761PubMedID: 12679420OAI: oai:DiVA.org:uu-72171DiVA: diva2:100082
Available from: 2007-03-12 Created: 2007-03-12 Last updated: 2010-05-19Bibliographically approved

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Sköldberg, FilipGrimelius, LarsGustafsson, JanRönnblom, AndersRorsman, FredrikKämpe, Olle
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Department of Medical SciencesDepartment of Genetics and PathologyDepartment of Women's and Children's Health
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Journal of Clinical Endocrinology and Metabolism
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