Glutamate decarboxylase 65 autoantibody (GAD65Ab)

Glutamate decarboxylase 65 autoantibodies (GAD65Ab) are immunoglobulins that target the 65 kDa isoform of the enzyme glutamate decarboxylase, which catalyzes the synthesis of the inhibitory neurotransmitter GABA [1]. These autoantibodies serve as critical clinical biomarkers for the autoimmune destruction of pancreatic beta cells, making them essential for the diagnosis of Type 1 Diabetes Mellitus (T1D) and Latent Autoimmune Diabetes in Adults (LADA) [2]. In addition to their role in diabetes, high titers of GAD65Ab are strongly associated with rare neurological disorders such as Stiff-Person Syndrome (SPS) and cerebellar ataxia, where they are believed to impair GABAergic signaling [3]. While the autoantibodies themselves are often considered markers of disease rather than the primary pathogenic drivers in diabetes, they are the focus of therapeutic strategies aimed at preserving beta-cell function [4]. For example, the investigational drug Diamyd (recombinant human GAD65) acts as an antigen-specific immunotherapy to induce immune tolerance and reduce the autoimmune attack associated with these antibodies [5]. Other treatments, such as Rituximab for B-cell depletion or intravenous immunoglobulin (IVIG) for antibody neutralization, are used to manage the neurological manifestations associated with high GAD65Ab levels [6]. Sources: [1] https://www.ncbi.nlm.nih.gov/books/NBK557789/ [2] https://pubmed.ncbi.nlm.nih.gov/30135123/ [3] https://www.ninds.nih.gov/health-information/disorders/stiff-person-syndrome [4] https://www.frontiersin.org/articles/10.3389/fimmu.2020.00131/full [5] https://www.diamyd.com/docs/pressRel.aspx?pressRelID=5012 [6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463353/

Other names

GADAAnti-GAD65Glutamic acid decarboxylase 65 antibodyGAD65-Ab

Antigen-specific immunotherapy to induce tolerance, B-cell depletion to reduce antibody production, and direct neutralization or removal of circulating autoantibodies.