Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes

Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system (CNS) and outside of the CNS, found in the highest concentrations in immune cells and pancreatic beta-cells. GABA is gaining increasing interest in diabetes research due to its immune-modulatory and beta-cell stimulatory effects and is a highly interesting drug candidate for the treatment of type 1 diabetes (T1D). GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD), one of the targets for autoantibodies linked to T1D. Using mass spectrometry, we have quantified the endogenous circulating levels of GABA in patients with new-onset and long-standing T1D and found that the levels are unaltered when compared to healthy controls, i.e., T1D patients do not have a deficit of systemic GABA levels. In T1D, GABA levels were negatively correlated with IL-1 beta, IL-12, and IL-15 15 and positively correlated to levels of IL-36 beta and IL-37. Interestingly, GABA levels were also correlated to the levels of GAD-autoantibodies. The unaltered levels of GABA in T1D patients suggest that the GABA secretion from beta-cells only has a minor impact on the circulating systemic levels. However, the local levels of GABA could be altered within pancreatic islets in the presence of GAD-autoantibodies.

Heidenhain variant sporadic Creutzfeldt-Jakob disease diagnosed as an autoimmune encephalitis due to a false-positive GAD autoantibody

A 64-year-old man presented with a subacute history progressive visual field defects, illusions and misperceptions. An initial MRI brain revealed a right occipital signal abnormality on diffusion-weighted imaging (DWI) with serum glutamic acid decarboxylase (GAD) autoantibodies markedly elevated. A diagnosis of autoimmune encephalitis was made, with the patient being treated with intravenous immunoglobulin. One month after discharge, the patient represented with worsening frank and well-formed visual hallucinations, ataxia and progressive cognitive impairment. Progress MRI displayed characteristic T2 ribboning on diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences, along with periodic sharp wave complexes on electroencephalogram (EEG) and a raised CSF protein 14-3-3. Repeat serum, as well as cerebrospinal fluid (CSF), GAD antibodies were again markedly elevated as measured by ELISA (RSR, Cardiff, UK), although archival CSF from the original presentation as well as CSF from the second presentation had undetectable GAD autoantibodies as measured via radioimmunoassay (DIAsource, Ottignies-Louvain-la-Neuve, Belgium). Creutzfeldt-Jakob disease was confirmed at autopsy.

PROGRESSION OF AUTOANTIBODIES ANTI-GAD AND ANTI-IA2 IN TYPE 1A DIABETICS AGED OF 5 TO 21 YEARS IN CÔTE D’IVOIRE

BackgroundDiabetes autoantibodies are indispensable markers of diabetes classification.Objectiveto research autoantibodies anti-GAD and anti-IA2 in type 1A diabetics (T1D) aged 5 to 21 years, and to follow the progression of these autoantibodies in T1D patients, in Côte d’Ivoire.MethodsThe study population composed of 28 T1D patients, aged 5 to 21 years. T1D were followed up in two diabetes care centers in Abidjan district, Endocrinology departments of U.H.C of Yopougon and Treichville. Anti-GAD and anti-IA2 autoantibodies were researched by ELISA.Resultsanti-GAD and anti-IA2 were present in T1D and their siblings. After 2 years of diabetes, the titer of the anti-GAD autoantibodies increased to the mean value of 677.10 ± 353.20 IU / ml. Then, a fall of the anti-GAD autoantibodies until the cancellation was observed from the 8th to the 9th with values of 117 IU / ml to 10.14 IU / ml. Anti-IA2 autoantibodies fall at 9th year of diabetes with a value of 55.10 IU / ml.Conclusionanti-GAD and anti-IA2 autoantibodies persist after 9 years of diabetes, causing total destruction over time of the pancreatic β-cell mass in patients from Côte d’Ivoire, leading them to the death.