Analysis of antibody reactivity against cysteine sulfinic acid decarboxylase, a pyridoxal phosphate-dependent enzyme, in endocrine autoimmune disease.
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.
Sköldberg
Filip
F
Department of Medical Sciences, Uppsala University, University Hospital, 751 85 Uppsala, Sweden. Filip.Skoldberg@medsci.uu.se
Rorsman
Fredrik
F
Perheentupa
Jaakko
J
Landin-Olsson
Mona
M
Husebye
Eystein S
ES
Gustafsson
Jan
J
Kämpe
Olle
O
D000224:Addison Disease / Q000276:immunology; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D002262:Carboxy-Lyases / Q000276:immunology*; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006640:Histidine Decarboxylase / Q000276:immunology; D006801:Humans; D007527:Isoenzymes / Q000276:immunology; D008297:Male; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology*; D011732:Pyridoxal Phosphate / Q000378:metabolism; D015531:Radioimmunoprecipitation Assay
D001323:Autoantibodies; D007527:Isoenzymes; D011732:Pyridoxal Phosphate; D002262:Carboxy-Lyases; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D006640:Histidine Decarboxylase; D001142:Aromatic-L-Amino-Acid Decarboxylases; C019972:sulfoalanine decarboxylase