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August 2015

Association of Paraneoplastic Neurological Disorders With Glutamic Acid Decarboxylase Antibodies

Author Affiliations
  • 1Epilepsy Centre Bethel, Krankenhaus Mara, Bielefeld, Germany
JAMA Neurol. 2015;72(8):861-862. doi:10.1001/jamaneurol.2015.1068

An increasing number of antineural IgG antibodies have been detected since the 1980s in patients with autoimmune central nervous system disease. Antibodies to intracellular antigens were initially found and antibodies to antigens on the neural surface have now been identified. Antibodies to the intracellular enzyme glutamic acid decarboxylase (GAD) were one of the earliest antibodies discovered.1 However, not all antibodies have the same value. This means that not all are pathogenic, specific for defined syndromes, and indicative for responsiveness to immunological treatment. Antibodies to the N-methyl-d-aspartate receptor and defined antigens in the voltage-gated potassium channel complex, such as leucine-rich glioma inactivated protein 1 and contactin-associated protein 2 (most likely the antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, the γ-aminobutyric acid B receptor, the glycine receptor, and others as well), are high-rank antibodies in that sense. However, other antibodies have their flaws because they lack 1 or more of these criteria. Antibodies to GAD are quite specific and are found in stiff-man syndrome, cerebellar ataxia, limbic encephalitis, and temporal lobe epilepsy.2 Specificity beyond 1 single syndrome is not uncommon. Even the high-rank antibodies are not entirely specific, as observed in the N-methyl-d-aspartate receptor antibodies.3,4 However, as already discussed in the Solimena et al article,1 the intracellular location of GAD makes an in vivo immunological reaction unlikely; GAD antibodies are probably not pathogenic on their own.1 The response of GAD antibodies to treatment is not as effective as, for example, antibodies to elements of the voltage-gated potassium channel complex.5 Taken together, GAD antibodies, even if they are high titer, are somehow considered second-class antibodies.