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Analysis of Antibody Reactivity against Cysteine Sulfinic Acid Decarboxylase, A Pyridoxal Phosphate-Dependent Enzyme, in Endocrine Autoimmune Disease

Departments of Medical Sciences (F.S., F.R., O.K.) and Women’s and Children’s Health (J.G.), Uppsala University, University Hospital, 751 85 Uppsala, Sweden; Hospital for Children and Adolescents (J.P.), University of Helsinki, 00029 Helsinki, Finland; Department of Medicine (M.L.-O.), Lund University, 221 85 Lund, Sweden; and Division of Endocrinology, Institute of Medicine (E.S.H.), Haukeland Hospital, 5021 Bergen, Norway

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

The structurally related group II pyridoxal phosphate (PLP)-dependent amino acid decarboxylases glutamic acid decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC), and histidine decarboxylase (HDC) are known autoantigens in endocrine disorders. We report, for the first time, the prevalence of serum autoantibody reactivity against cysteine sulfinic acid decarboxylase (CSAD), an enzyme that shares 50% amino acid identity with the 65- and 67-kDa isoforms of GAD (GAD-65 and GAD-67), in endocrine autoimmune disease. Three of 83 patients (3.6%) with autoimmune polyendocrine syndrome type 1 (APS1) were anti-CSAD positive in a radioimmunoprecipitation assay. Anti-CSAD antibodies cross-reacted with GAD-65, and the anti-CSAD-positive sera were also reactive with AADC and HDC. The low frequency of anti-CSAD reactivity is in striking contrast to the prevalence of antibodies against GAD-65, AADC, and HDC in APS1 patients, suggesting that different mechanisms control the immunological tolerance toward CSAD and the other group II decarboxylases. Moreover, CSAD may be a useful mold for the construction of recombinant chimerical antigens in attempts to map conformational epitopes on other group II PLP-dependent amino acid decarboxylases.

This work was supported in part by the Swedish 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 Lennander Foundation, and the Agnes and Mac Rudberg Foundation.

Abbreviations: AADC, Aromatic L-amino acid decarboxylase; APS1, autoimmune polyendocrine syndrome type 1; CSAD, cysteine sulfinic acid decarboxylase; GAD, glutamic acid decarboxylase; HDC, histidine decarboxylase; IDDM, insulin-dependent diabetes mellitus; PLP, pyridoxal phosphate.

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