High Titers of Autoantibodies to Glutamate Decarboxylase in Type 1 Diabetes Patients: Epitope Analysis and Inhibition of Enzyme Activity |
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| Institution: | 1. Department of Medicine, University of Washington, Seattle, Washington;2. Department of Rehabilitation Medicine, University of Washington, Seattle, Washington;3. University of Washington Medical Center, Seattle, Washington;4. UW GenOM Project at the University of Washington, Seattle, Washington;5. Department of Neurology, University of Washington, Seattle, Washington;1. Boston Children’s Hospital, Division of Endocrinology, Boston, Massachusetts;2. Case Western Reserve University School of Medicine, Cleveland, Ohio;3. Boston University School of Medicine, Division of Endocrinology, Diabetes, and Nutrition, Boston, Massachusetts.;1. Division of Endocrinology, “V. Fazzi” Hospital, Lecce, Italy;2. Endocrine Unit and Thyroid Diseases Center, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia;3. Department of Endocrinology and Metabolism, Thessaloniki, Greece;4. Department of Pathology,“V. Fazzi” Hospital, Lecce, Italy;5. Institute of Pathology, Locarno, Switzerland;6. Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland;7. Department of Pathology, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy;1. Department of Gastroenterology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India;2. Department of Endocrinology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.;3. DDepartment of Radiology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India;4. Department of Surgical Endocrinology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.;1. The John A. Hartford Foundation Center of Excellence in Geriatrics, Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, the;2. Department of Obstetrics, Gynecology & Women’s Health, John A. Burns School of Medicine, University of Hawaii, the;3. Kuakini Medical Center, and the;4. Miki Medical Associates, Honolulu, Hawai.;1. Department of Endocrinology and Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio;2. Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio;1. Division of Neuroendocrinology, Beaumont Hospital & the RCSI Medical School, Dublin, Ireland. |
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| Abstract: | ObjectiveAutoantibodies 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.MethodsWe 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.ResultsOverall, 43% (43/100) of patients had detectable GAD65Ab titers (median = 400 U/mL, range: 142250,000 U/mL). The GAD65Ab titers in 10 type 1 diabetes patients exceeded the 90th percentile of the cohort (2,000250,000 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.ConclusionsBased on our findings, we suggest that neurological disorders with high GAD65Ab titers are more frequent in type 1 diabetes patients than currently recognized. (Endocr Pract. 2013;19:663-668) |
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