Inhibition of aromatic L-amino acid decarboxylase activity by human autoantibodies

A full-length rat cDNA clone encoding aromatic L-amino acid decarboxylase (AADC) (E.C. 4.1.1.28) was used for in vitro transcription and translation. The enzyme had catalytic activity (0. 2 pmol serotonin/microl lysate per min), and was stimulated 2.5-fold by the addition of excess pyridoxal phosphate. On size exclusion chromatography, AADC eluted as a single activity peak with an apparent mol. wt of 93 kD. This activity peak was immunoprecipitated by sera from patients with autoimmune polyendocrine syndrome type I (APS I) containing autoantibodies against AADC. Serum and purified IgG from these patients inhibited the enzyme activity (non-competitively) by 10-80%, while sera from APS I patients without autoantibodies and controls did not. This finding confirms and extends previous observations that APS I patients have inhibitory antibodies against key enzymes involved in neurotransmitter biosynthesis.