OBJECTIVE: Autoantibodies to glutamate decarboxylase (GAD65Ab) are found in patients with autoimmune neurological disorders or type 1 diabetes. The correct diagnosis of GAD65Ab-associated neurological disorders is often delayed by the variability of symptoms and a lack of diagnostic markers. We hypothesized that the frequency of neurological disorders with high GAD65Ab titers is significantly higher than currently recognized. METHODS: We analyzed GAD65Ab titer, GAD65 enzyme activity inhibition, and GAD65Ab epitope pattern in a cohort of type 1 diabetes patients (n = 100) and correlated our findings with neurological symptoms and diseases. RESULTS: Overall, 43% (43/100) of patients had detectable GAD65Ab titers (median = 400 U/mL, range: 142-250,000 U/mL). The GAD65Ab titers in 10 type 1 diabetes patients exceeded the 90th percentile of the cohort (2,000-250,000 U/mL). Sera of these 10 patients were analyzed for their GAD65Ab epitope specificity and their ability to inhibit GAD65 enzyme activity in vitro. GAD65Ab of 5 patients inhibited the enzyme activity significantly (by 34-55%). Three patients complained of muscle stiffness and pain, which was documented in 2 of these patients. CONCLUSIONS: Based on our findings, we suggest that neurological disorders with high GAD65Ab titers are more frequent in type 1 diabetes patients than currently recognized.
OBJECTIVE: Autoantibodies to glutamate decarboxylase (GAD65Ab) are found in patients with autoimmune neurological disorders or type 1 diabetes. The correct diagnosis of GAD65Ab-associated neurological disorders is often delayed by the variability of symptoms and a lack of diagnostic markers. We hypothesized that the frequency of neurological disorders with high GAD65Ab titers is significantly higher than currently recognized. METHODS: We analyzed GAD65Ab titer, GAD65 enzyme activity inhibition, and GAD65Ab epitope pattern in a cohort of type 1 diabetespatients (n = 100) and correlated our findings with neurological symptoms and diseases. RESULTS: Overall, 43% (43/100) of patients had detectable GAD65Ab titers (median = 400 U/mL, range: 142-250,000 U/mL). The GAD65Ab titers in 10 type 1 diabetespatients exceeded the 90th percentile of the cohort (2,000-250,000 U/mL). Sera of these 10 patients were analyzed for their GAD65Ab epitope specificity and their ability to inhibit GAD65 enzyme activity in vitro. GAD65Ab of 5 patients inhibited the enzyme activity significantly (by 34-55%). Three patients complained of muscle stiffness and pain, which was documented in 2 of these patients. CONCLUSIONS: Based on our findings, we suggest that neurological disorders with high GAD65Ab titers are more frequent in type 1 diabetespatients than currently recognized.
Authors: C S Hampe; L P Hammerle; L Bekris; E Ortqvist; I Kockum; O Rolandsson; M Landin-Olsson; C Törn; B Persson; A Lernmark Journal: J Clin Endocrinol Metab Date: 2000-12 Impact factor: 5.958
Authors: Andrew McKeon; Maisha T Robinson; Kathleen M McEvoy; Joseph Y Matsumoto; Vanda A Lennon; J Eric Ahlskog; Sean J Pittock Journal: Arch Neurol Date: 2012-02
Authors: Subrata Chattopadhyay; Masumi Ito; Jonathan D Cooper; Andrew I Brooks; Timothy M Curran; James M Powers; David A Pearce Journal: Hum Mol Genet Date: 2002-06-01 Impact factor: 6.150
Authors: J Honnorat; A Saiz; B Giometto; A Vincent; L Brieva; C de Andres; J Maestre; N Fabien; A Vighetto; R Casamitjana; C Thivolet; B Tavolato; J Antoine; P Trouillas; F Graus Journal: Arch Neurol Date: 2001-02