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.