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: Filip Sköldberg, Guida M Portela-Gomes, Lars Grimelius, Gunnar Nilsson, Jaakko Perheentupa, Corrado Betterle, Eystein S Husebye, Jan Gustafsson, Anders Rönnblom, Fredrik Rorsman, Olle Kämpe
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 88 Issue 4 Pg. 1445-52 (Apr 2003) ISSN: 0021-972X [Print] United States
• PMID: 12679420 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Autoantigens
• Pyridoxal Phosphate
• Histidine Decarboxylase

Topics

• 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)