High titers of autoantibodies to glutamate decarboxylase in type 1 diabetes patients: epitope analysis and inhibition of enzyme activity.

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.

[Active tracheo-bronchial caseous tuberculosis. Ten patients]. / La tuberculose active caséeuse trachéo-bronchique. A propos de 10 cas.

BACKGROUND: We report 10 cases of active endobronchial tuberculosis in female patients. PATIENTS AND METHODS: Diagnosis of endobronchial tuberculosis was established by demonstrating the presence of Koch bacilli in the bronchial washings or at pathology examination of a bronchial mucosa biopsy. Follow-up was available for 5 of the 10 cases. RESULTS: These women were aged 19 to 756 years. Clinical signs included persistent cough (n=10), wheezing (n=10), dyspnea (n=5), dysphonia (n=4) and fever (n=8). Chest x-ray was normal in 4 cases but showed condensation in 4 others with infiltration of the superior lobe in 2 cases. Bronchoscopy findings were characteristic with a thick layer of white caseum on the mucosa. Koch bacilli were found in all bronchial wash specimens. Pathology examination confirmed the diagnosis of tuberculosis in 5 of the 10 cases.