An autoantibody to GAD65 in sera of patients with juvenile neuronal ceroid lipofuscinoses.

Abstract

Juvenile neuronal ceroid lipofuscinoses (Batten disease) is a neurodegenerative disease that presents in early childhood. The main features of this disease are failure of psychomotor development, impaired vision, and seizures. Death usually occurs in late teens to early twenties. Batten disease is an autosomal-recessive disorder, resulting from mutations in the CLN3 gene product.1 Genetic testing can identify the most common mutation in CLN3 , a 1.02-kb deletion. However this accounts for only about 74% of the mutations identified thus far in CLN3 ,1,2⇓ and because identification of rarer point mutations in CLN3 is often difficult, another diagnostic tool would be useful. We have previously shown that a mouse model for Batten disease, i.e., cln3-knockout mice, and eight individuals with Batten disease have an autoimmune response to GAD65.3 In the same study we reported that a total of 20 individuals with Batten disease tested positive for the presence of autoantibodies to glutamate decarboxylase, GAD65. Furthermore, studies in the mouse revealed that the autoantibody to GAD65 is associated with astrocytic hypertrophy in the brain. Moreover, the cln3-knockout mice that have the autoimmune response to GAD65 have decreased activity of glutamic acid decarboxylase and consequently elevated levels of presynaptic glutamate in the brain.3 It has been suggested that a preferential loss of GABAergic neurons is a major factor in the progression of Batten disease.4 It is therefore plausible to predict that the GAD65 autoantibody and its resultant effects on the brain are possible contributors to the pathology associated …