title: Identification of alpha-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 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.
authors.affiliation: Center for Aging and Developmental Biology, Aab Institute of Biomedical Science, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Castaneda
authors.forename: David A
authors.initials: DA
authors.lastname: Pearce
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism*; D002648:Child; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D008099:Liver / Q000378:metabolism; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009472:Neuronal Ceroid-Lipofuscinoses / Q000276:immunology* / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D053719:Tandem Mass Spectrometry / Q000379:methods; D000509:alpha-Fetoproteins / Q000032:analysis* / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C102229:CLN3 protein, mouse; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D000509:alpha-Fetoproteins