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Histidine Decarboxylase, a Pyridoxal Phosphate-Dependent Enzyme, Is an Autoantigen of Gastric Enterochromaffin-Like Cells

2003; Oxford University Press; Volume: 88; Issue: 4 Linguagem: Inglês

10.1210/jc.2002-021761

1945-7197

Filip Sköldberg, Guida Maria Portela‐Gomes, Lars Grimelius, Gunnar Nilsson, Jaakko Perheentupa, Corrado Betterle, Eystein S. Husebye, Jan Gustafsson, Anders Rönnblom, Fredrik Rorsman, Olle Kämpe,

Hormonal Regulation and Hypertension

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.