Autoantibodies from patients with idiopathic ataxia bind to M-phase phosphoprotein-1 (MPP1).
In an attempt to identify unique disease-related autoantibodies, the serum from an ataxia and sensory neuropathy patient was used as a probe to isolate 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 yielded a recombinant protein that migrated in SDS-PAGE at approximately 97 kd. This protein was immunoprecipitated by the prototype human serum, by an immune guinea pig anti-MPP1 serum, but not by normal human serum or preimmune guinea pig serum. Western blot analysis of HeLa cell proteins showed that the prototype human serum and immune guinea pig antiserum recognized an approximately 225-kd protein, suggesting that the isolated clone contained a partial cDNA. By indirect immunofluorescence, the affinity-purified antibody and a guinea pig antiserum reacted with nuclei of interphase HEp-2 cells and the cytoplasm of certain neuronal cells. Sera from 10 of 25 unselected patients with ataxia, 1 of 30 patients with peripheral neuropathy, 1 of 50 multiple sclerosis patients, 0 of 20 amyotrophic lateral sclerosis, 0 of 10 children with postviral ataxia, 0 of 10 systemic lupus erythematosus patients, 0 of 3 patients with hereditary cerebellar ataxia, 0 of 8 with ataxia telangiectasia, and 0 of 30 age- and gender-matched controls immunoprecipitated 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.
Fritzler
M J
MJ
Department of Medicine, University of Calgary, Canada. fritzler@ucalgary.ca
Kerfoot
S M
SM
Feasby
T E
TE
Zochodne
D W
DW
Westendorf
J M
JM
Dalmau
J O
JO
Chan
E K
EK
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001259:Ataxia / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001483:Base Sequence; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology*; D002648:Child; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D016547:Kinesins; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D009687:Nuclear Proteins; D010750:Phosphoproteins; C438388:KIF20B protein, human; D016547:Kinesins