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

Neurobiol Dis. 2008 Jan;29(1):92-102. doi: 10.1016/j.nbd.2007.08.007. Epub 2007 Aug 25.


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 alpha-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Animals, Newborn
  • Autoantibodies / metabolism
  • Autoantigens / metabolism*
  • Child
  • Disease Models, Animal
  • Electrophoresis, Gel, Two-Dimensional / methods
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental / physiology
  • Humans
  • Liver / metabolism
  • Liver Function Tests / methods
  • Male
  • Membrane Glycoproteins / deficiency
  • Mice
  • Mice, Knockout
  • Molecular Chaperones
  • Neuronal Ceroid-Lipofuscinoses / immunology*
  • Neuronal Ceroid-Lipofuscinoses / metabolism*
  • Sequence Analysis, Protein
  • Tandem Mass Spectrometry / methods
  • alpha-Fetoproteins / analysis*
  • alpha-Fetoproteins / metabolism*


  • Autoantibodies
  • Autoantigens
  • CLN3 protein, mouse
  • Membrane Glycoproteins
  • Molecular Chaperones
  • alpha-Fetoproteins