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

Departments of Medical Sciences (F.S., A.R., F.R., O.K.), Women’s and Children’s Health (J.G.), and Genetics and Pathology (G.M.P.-G., L.G., G.N.), Uppsala University, University Hospital, 751 85 Uppsala, Sweden; Hospital for Children and Adolescents (J.P.), University of Helsinki, 00029 Helsinki, Finland; Department of Medical and Surgical Sciences (C.B.), University of Padova, 35128 Padova, Italy; and Division of Endocrinology (E.S.H.), Institute of Medicine, Haukeland Hospital, 5021 Bergen, Norway

Address all correspondence and requests for reprints to: Dr. Filip Sköldberg, Department of Medical Sciences, Uppsala University, University Hospital, 751 85 Uppsala, Sweden. E-mail: Filip.Skoldberg{at}medsci.uu.se.

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.

This work was supported in part by the Medical Research Council, the Torsten and Ragnar Söderberg Foundation, the Petrus and Augusta Hedlund Foundation, the Swedish Medical Society, the Claes Groschinsky Memorial Foundation, the Agnes and Mac Rudberg Foundation, the Tore and Wera Cornell Foundation, and the Professor Nanna Svartz’ Foundation.

Abbreviations: AADC, Aromatic L-amino acid decarboxylase; AIRE, AIRE autoimmune regulator; APS1, autoimmune polyendocrine syndrome type 1; CgA, chromogranin A; EC, enterochromaffin; ECL, enterochromaffin-like; GAD, glutamic acid decarboxylase; HDC, histidine decarboxylase; IDDM, insulin-dependent diabetes mellitus; MBP, maltose binding protein; TPH, tryptophan hydroxylase; VMAT-2, vesicular monoamine transporter-2.

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