Serum Glutamic Acid Decarboxylase Antibody Research Articles

A comparative study of multiple biomarkers levels in complicated versus noncomplicated type 2 diabetic patients.

The prevalence of diabetes mellitus is growing globally and the management of diabetes is a critical issue for public health. This study aimed to analyze the concentration of different biomarkers in patients with type 2 diabetes mellitus (T2DM) without complication, T2DM patients with complication (T2DM+C), and compared to healthy controls (HC). For this aim, there were 164 participants: 59 T2DM, 60 T2DM+C, and 45 HC. Venous blood was collected and the levels of Hemoglobin A1C (HbA1C), fasting blood glucose, Interleukin-31 (IL-31), IL-35, glutamic acid decarboxylase antibody (GADA), developmental locus-1 (Del-1), fibroblast growth factor-9 (FGF-9) and FGF-18) and lipid profile (total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride) were analyzed. Results showed that IL-31 was significantly higher in T2DM compared to HC (p<0.0001), and compared to T2DM+C (p<0.0001). IL-31 was significantly lower in T2DM+C than HC (p=0.009). The level of serum GADA was significantly elevated in T2DM compared to HC (p=0.0009), and T2DM+C (p=0.03). There was a significant correlation between (IL-31, IL-35, GADA, Del-1, FGF-9 and FGF-18). The duration of having diabetes was significantly longer in T2DM+C compared to T2DM (p<0.0001). However, there was no significant difference in the level of HBA1C% between T2DM+C and T2DM patients (p=0.98). In conclusion, there were significant differences in biomarker concentrations between all three groups. This indicates that the monitoring of multiple biomarkers may be of value in the controlling of T2DM in the future.

When the rhythm moves you

A 47-year-old lady presented with a 6-year history of increasing refractory seizures and scoliosis despite trials of multiple anti-epileptic drugs(AEDs). She described seizures of temporal lobe(TLE) semiology provoked mainly by music which evoked elation. These musicogenic reflex seizures (MRS) were occurring up to twice weekly.CT and MRI brain, paraspinal EMG, and routine EEG were unremarkable. Provoked EEG captured a gen- eralised seizure with focal left mid-anterior temporal focus with rapid bilateral spreading within 2 minutes of playing a piece of music and lasted for 90 seconds, followed by a prolonged post-ictal phase. Auto- antibody screen revealed persistently elevated and rising serum GAD-Ab(glutamic acid decarboxylase antibodies) at 11618 U/mL with GAD positive on CSF testing. CT body, PET and transvaginal ultrasound revealed no significant abnormalities. Plasmapheresis was trialled with some effect.We present a rare case of GAD-Ab mediated MRS. MRS are well described, with 9% mediated by GAD-Ab. This mechanistically accounts for the limbic MRS semiology. We highlight the importance of GAD-Ab screening for refractory new onset TLE in an adult, with high serum GAD-Ab titre (≥2000 U/mL) and evidence of intrathecal synthesis. Unlike other immune-mediated epilepsies, GAD-Ab-mediated epilepsy responds poorly to AEDs and may require immunosuppression with rituximab or cyclophosphamide.

Serum IL-17A concentration and a IL17RA single nucleotide polymorphism contribute to the risk of autoimmune type 1 diabetes.

Interleukin (IL)-17 is associated with autoimmunity. This study aimed to affirm the role of IL-17A, IL-17F and single nucleotide polymorphisms (SNPs) in genes related to them and their receptors in autoimmune type 1 diabetes (T1D) for Chinese population. In this study, 130 patients with autoimmune T1D and 140 non-T1D controls were included for analysis. Clinical and biochemical data were collected, and serum levels of IL-17A, IL-17F, IL-6, and high-sensitivity C reactive protein were measured using ELISA. The SNPs rs2275913, rs8193036, rs3819025, rs763780, rs879577, rs4819554, and rs708567 were genotyped using the SNaPshot assay. IL-17A levels were higher in patients with autoimmune T1D than in controls (median [IQR] 28.83[37.38] vs. 16.68[8.10], p<0.001) and high IL-17A was a risk factor for autoimmune T1D (odds ratio (OR), 1.013; 95% CI, 1.003-1.023; p=0.013) after adjusting for confounding factors. Linear regression analysis revealed that log10 IL-17A levels were independently associated with fasting C-peptide, IL-6, body mass index, and IL-17F. However, no independent association was found between IL-17F and autoimmune T1D. The GG genotype of SNP rs4819554 in the interleukin 17 receptor A (IL17RA) gene was associated with a decreased risk of autoimmune T1D (OR, 0.458; 95% CI, 0.246-0.852; p=0.014) after adjusting for other confounders. The IL17RA rs4819554GG genotype was negatively correlated with serum glutamic acid decarboxylase antibody appearance (p<0.05). Increased serum IL-17A, but not IL-17F, is a risk factor for autoimmune T1D. The GG genotype of IL17RA rs4819554 might decrease the risk for autoimmune T1D.

Evaluating the Prognostic Value of Islet Autoantibody Monitoring in Islet Transplant Recipients with Long-Standing Type 1 Diabetes Mellitus.

(1) Background: The correlation between titers of islet autoantibodies (IAbs) and the loss of transplanted islets remains controversial. We sought to evaluate the prognostic utility of monitoring IAbs in diabetic patients after islet transplantation (ITx); (2) Methods: Twelve patients with Type 1 diabetes mellitus and severe hypoglycemia underwent ITx. Serum concentration of glutamic acid decarboxylase (GAD), insulinoma antigen 2 (IA-2), and zinc transport 8 (ZnT8) autoantibodies was assessed before ITx and 0, 7, and 75 days and every 3 months post-operatively; (3) Results: IA-2A (IA-2 antibody) and ZnT8A (ZnT8 antibody) levels were not detectable before or after ITx in all patients (median follow-up of 53 months (range 24–61)). Prior to ITx, GAD antibody (GADA) was undetectable in 67% (8/12) of patients. Of those, 75% (6/8) converted to GADA+ after ITx. In 67% (4/6) of patients with GADA+ seroconversion, GADA level peaked within 3 months after ITx and subsequently declined. All patients with GADA+ seroconversion maintained long-term partial or complete islet function (insulin independence) after 1 or 2 ITx. There was no correlation between the presence of IAb-associated HLA haplotypes and the presence of IAbs before or after ITx; (4) Conclusions: There is no association between serum GADA trends and ITx outcomes. IA-2A and ZnT8A were not detectable in any of our patients before or after ITx.

Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study...

Evaluation of Glutamic Acid Decarboxylase Antibody Levels in Patients with Juvenile Myoclonic Epilepsy and Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

Several clinical studies have been conducted to investigate the role of autoantibodies and immunological mechanisms in the etiology of treatment-resistant epilepsy in recent years. Some immunological treatments have been suggested as a result of these studies. In this study, we aimed to investigate the role of autoimmunity in partial and idiopathic generalized epilepsy and determine the relationship between drug resistance and autoimmune antibodies. Twenty-eight patients (24 treatment-responsive and 4 treatment-resistant) with juvenile myoclonic epilepsy (JME), 26 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLEHS) resistant to antiepileptic drug treatment, and 26 age-matched healthy control subjects were included in a two-year cross sectional study. Glutamic acid decarboxylase antibody (GADA) levels were measured with a radioimmunoassay method in the serum of the included subjects. High GADA titers were detected in 2 patients with JME (7.1%), 1 patient with MTLEHS (3.8%), and 1 healthy subject (3.8%). There was no statistically significant difference among the groups regarding the serum GADA level. Although a limited number of drug-resistant patients with JME our study did not show relationships among anti-GADAs, both epileptic syndromes and drug resistance. Because we did not determine any significant relationship between GADA levels and JME or MTLEHS, we do not recommend analysis of serum GADA levels in routine examinations where there is no evidence to suggest risk factors for autoimmunity.

Neuronal Surface and Glutamic Acid Decarboxylase Autoantibodies in Nonparaneoplastic Stiff Person Syndrome

High titers of autoantibodies to glutamic acid decarboxylase (GAD) are well documented in association with stiff person syndrome (SPS). Glutamic acid decarboxylase is the rate-limiting enzyme in the synthesis of γ-aminobutyric acid (GABA), and impaired function of GABAergic neurons has been implicated in the pathogenesis of SPS. Autoantibodies to GAD might be the causative agent or a disease marker. To investigate the characteristics and potential pathogenicity of GAD autoantibodies in patients with SPS and related disorders. Retrospective cohort study and laboratory investigation. Weatherall Institute of Molecular Medicine, University of Oxford. Twenty-five patients with SPS and related conditions identified from the Neuroimmunology Service. Neurological examination, serological characterization and experimental studies. Characterization of serum GAD antibodies from patients with SPS and evidence for potential pathogenicity. We detected GAD autoantibodies at a very high titer (median, 7500 U/mL) in 19 patients (76%), including all 12 patients with classic SPS. The GAD autoantibodies were high affinity (antibody dissociation constant, 0.06-0.78 nmol) and predominantly IgG1 subclass. The patients’ autoantibodies co-localized with GAD on immunohistochemistry and in permeabilized cultured cerebellar GABAergic neurons, as expected, but they also bound to the cell surface of unpermeabilized GABAergic neurons. Adsorption of the highest titer (700 000 U/mL) serum with recombinant GAD indicated that these neuronal surface antibodies were not directed against GAD itself. Although intraperitoneal injection of IgG purified from the 2 available GAD autoantibody–ositive purified IgG preparations did not produce clinical or pathological evidence of disease, SPS and control IgG were detected in specific regions of the mouse central nervous system, particularly around the lateral and fourth ventricles. Autoantibodies to GAD are associated with antibodies that bind to the surface of GABAergic neurons and that could be pathogenic. Moreover, in mice, human IgG from the periphery gained access to relevant areas in the hippocampus and brainstem. Identification of the target of the non-GAD antibodies and peripheral and intrathecal transfer protocols, combined with adsorption studies, should be used to demonstrate the role of the non-GAD IgG in SPS.

Non-Convulsive Status Epilepticus Associated With Glutamic Acid Decarboxylase Antibody

Autoimmune encephalitis associated with glutamic acid decarboxylase antibodies (GAD-Ab) often presents with treatment-resistant partial seizures, as well as other central nervous system symptoms. In contrast to several other well-characterized autoantibodies, GAD-Ab has very rarely been associated with status epilepticus. We report a 63-year-old woman initially admitted with somnolence and psychiatric findings. The EEG findings, of generalized and rhythmical slow spike-wave activity over the posterior regions of both hemispheres, together with the clinical deterioration in responsiveness, led to the diagnosis of non-convulsive status epilepticus. Investigation of a broad panel of autoantibodies, revealed only increased serum GAD-Ab levels. Following methylprednisolone and intravenous immunoglobulin treatments, the patient's neurological symptoms improved, EEG findings disappeared and GAD-Ab levels significantly decreased. GAD-Ab should be added to the list of anti-neuronal antibodies associated with non-convulsive status epilepticus. Disappearance of clinical findings and seroreversion after immunotherapy suggest that GAD-Ab might be involved in seizure pathogenesis.

Autoantibodies to glutamic acid decarboxylase in patients with epilepsy are associated with low cortical GABA levels

Antibodies to glutamic acid decarboxylase (GAD), the major pathway for the synthesis of c-aminobutyric acid(GABA) in humans, are found at elevated levels in a subgroup of patients with chronic epilepsy. To test whether the antibodies were associated with changes in cortical GABA levels we used magnetic resonance spectroscopy. Four patients with epilepsy and high serum GAD antibody levels (107-6,200 units/ml) and 10 healthy controls were recruited. A 3T GABA-optimized spectrum was obtained from a reproducible voxel in the cortex. Compared to the control group, the patient group had significantly lower GABA concentrations within the cortex. Demonstration of an association between high serum GAD antibodies and low cortical GABA levels in patients with epilepsy suggests that GAD antibodies are, at least, a marker of a specific disease process and support a role for immune-mediated GABAergic dysfunction.

Relationship between serum glutamic acid decarboxylase antibody titer and the first-phase insulin release in newly-diagnosed type 2 diabetic patients

To investigate the relationship between serum glutamic acid decarboxylase antibody (GAD-Ab)titer and the first-phase insulin release (1PH)in newly-diagnosed type 2 diabetic patients. 1053 newly-diagnosed type 2 diabetic patients were divided into 3 groups, including 71 individuals with GAD-Ab≥1 U/ml (positive group), 171 individuals with GAD-Ab ranging from 0 to 1 U/ml (negative-1 group), and 811 individuals with GAD-Ab=0 (negative-2 group). IPH was evaluated by arginine stimulation test. In the patients of negative-2, negative-1, and positive groups, the respective values of 1 PH were subsequently decreased significantly (P< 0. 01) , and the detection rates of the decreased insulin secretion were 74. 85%, 87. 13%, and 100%, respectively. Stepwise regression analysis indicated that disease duration, GAD-Ab titer, HbA_1C, and body mass index were the major independent contributing factors. The titer of GAD-Ab has an important impact on 1PH defect in type 2 diabetic patient. Detection of GAD-Ab not only provides an evidence for clinical type, but would also be helpful in determining the islet β-cell function. Key words: Diabetes mellitus; Glutamic acid decarboxylase antibody; Arginine stimulation test

Distribution of autoantibodies to glutamic acid decarboxylase across the spectrum of diabetes mellitus seen in South Africa.

This study investigated the association between glutamic acid decarboxylase antibodies (GAD-AB) and Type 1, Type 2, pancreatic and lipoatrophic diabetes mellitus (DM) in South African patients. Four groups were selected: group A, 100 Black Type 1 DM patients (age at onset < 35 years, body mass index (BMI) < 27 kg/m2 and insulin dependent within 1 year of presentation); group B, 80 Black Type 2 DM patients (age at onset > 35 years, BMI > 27 kg/m2 and controlled on oral hypoglycaemic agents for at least 1 year after presentation); group C, 10 patients of varying ethnicity with DM or impaired glucose tolerance secondary to chronic pancreatitis; group D, five patients of varying ethnicity with DM associated with total lipodystrophy. Fifty healthy Black control subjects were also studied (group E). Serum GAD-AB and random C-peptide levels were measured by radioimmunoassay. Mean C-peptide concentration was significantly lower in Type 1 DM patients than Type 2 DM patients (P < 0.00001). Forty-four patients with Type 1 DM were GAD-AB-positive compared to two patients with Type 2 DM. Two control subjects were also GAD-AB-positive. No patient in the other groups had a titre > 1 U/ml. Type 1 DM patients who were GAD-AB-positive did not differ from those who were GAD-AB-negative for age at onset, duration of DM or C-peptide concentrations. Auto-immune beta-cell destruction has an important role in the pathogenesis of Type 1 DM amongst African patients. However, Type 2 African DM patients and other diabetes subtypes are largely GAD-AB-negative.