Autoantibodies from patients with idiopathic ataxia bind to M-phase phosphoprotein-1 (MPP1)

Citation
Mj. Fritzler et al., Autoantibodies from patients with idiopathic ataxia bind to M-phase phosphoprotein-1 (MPP1), J INVES MED, 48(1), 2000, pp. 28-39
Citations number
88
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
JOURNAL OF INVESTIGATIVE MEDICINE
ISSN journal
1081-5589 → ACNP
Volume
48
Issue
1
Year of publication
2000
Supplement
S
Pages
28 - 39
Database
ISI
SICI code
1081-5589(200001)48:1<28:AFPWIA>2.0.ZU;2-0
Abstract
in an attempt to identify unique disease-related autoantibodies, the serum from an ataxia and sensory neuropathy patient was used as a probe to isolat e a 2.5-kd cDNA from a HeLa expression library. The nucleotide sequence was 99% identical to MPP1, a cell-cycle-related nuclear protein phosphorylated during mitosis, Expression of the cDNA in an in vitro translation system y ielded a recombinant protein that migrated in SDS-PAGE at approximate to 97 kd, This protein was immunoprecipitated by the prototype human serum, by a n immune guinea pig anti-MPP1 serum, but not by normal human serum or preim mune guinea pig serum, Western blot analysis of HeLa cell proteins showed t hat the prototype human serum and immune guinea pig antiserum recognized an approximate to 225-kd protein, suggesting that the isolated clone containe d a partial cDNA, By indirect immunofluorescence. the affinity-purified ant ibody and a guinea pig antiserum reacted with nuclei of interphase HEp-2 ce lls and the cytoplasm of certain neuronal cells, Sera from 10 of 25 unselec ted patients with ataxia, 1 of 30 patients with peripheral neuropathy, 1 of 50 multiple sclerosis patients. 0 of 20 amyotrophic lateral sclerosis, 0 o f 10 children with postviral ataxia, 0 of 10 systemic lupus erythematosus p atients, 0 of 3 patients with hereditary cerebellar ataxia, 0 of 8 with ata xia telangiectasia, and 0 of 30 age- and gender-matched controls immunoprec ipitated the recombinant MPP1 protein. None of the patients with anti-MPP1 antibodies had evidence of malignancy. This is the first report of MPP1 as a target autoantigen in patients with idiopathic ataxia.