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.