Identification of α-fetoprotein as an autoantigen in juvenile Batten disease

Abstract

Humoral autoimmunity against glutamic acid decarboxylase has been described in juvenile Batten disease patients and in the Cln3−/− mouse model. To obtain a more comprehensive understanding of the repertoire of antigens targeted, we examined the reactivity of Cln3−/− mouse sera to brain proteins from fetal, postnatal and adult rats. Among the candidate antigens identified was α-fetoprotein (AFP), a protein that has altered expression in several nervous system disorders and hepatic malignancies. Moreover, AFP levels were upregulated in the brains and livers of postnatal day 14 Cln3−/− animals. Sera from 31 juvenile Batten disease patients revealed the presence of anti-AFP autoantibodies in juvenile Batten disease male patients (12/13) and female patients (8/18). While these findings provide more evidence that autoimmunity is an active component of juvenile Batten disease, the gender-apparent difference evidenced by patients with regard anti-AFP antibodies may underlie variation in progression and clinical manifestations in this disorder.

Keywords

• Juvenile Batten disease
• Neuronal ceroid lipofuscinoses
• Alpha fetoprotein
• Autoimmunity
• Autoantibodies