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 ≈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 ≈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.
RopperAH, GorsonKC. Neuropathies associated with paraproteinemia. N Engl J Med1998; 338:1601–7.
7.
SpadaroM, AmendoleaMA, MazzucconiMG, FantozziR, Di LelloR, ZangariP, MasalaC. Autoimmunity in multiple sclerosis: study of a wide spectrum of autoantibodies. Mult Scler, 1999;5:121–5.
8.
KornbergAJ, PestronkA. The clinical and diagnostic role of anti-GM, antibody testing. Muscle Nerve1994;17:100–4.
9.
PestronkA, ChoksiR, BieserK, GoldsteinJM, AdlerCH, CaselliRJ, GeorgeEB. Treatable gait disorder and polyneuropathy associated with high titer serum IgM binding to antigens that copurify with myelin-associated glycoprotein. Muscle Nerve1994;17:1293–1300.
10.
SolimenaM, De CamilliP. Autoimmunity to glutamic acid decarboxylase (GAD) in stiff-man syndrome and insulin-dependent diabetes mellitus. Trends Neurosci1991;14:452–7.
11.
PelucchiA, CiceriE, ClementiF, MarazziniL, ForesiA, SherE. Calcium channel autoantibodies in myasthenic syndrome and small cell lung cancer. Am Rev Respir Dis1993;147:1229–32.
12.
LindseyJW, AlbersGW, SteinmanL. Recurrent transverse myelitis, myasthenia gravis, and autoantibodies. Ann Neurol1992;32: 407–9.
13.
ConnollyAM, DodsonWE, PrenskyAL, RustRS. Course and outcome of acute cerebellar ataxia. Ann Neurol1994;35:673–9.
14.
FifeTD, BalchRW. Disequilibrium of unknown cause in older people. Ann Neurol1993;34:694–702.
15.
VictorM, FerrendelliJA. The nutritional and metabolic diseases of the cerebellum: clinical and pathological aspects. In: FieldWS, WillisWD, eds. The cerebellum in health and disease. St. Louis: Warren H. Gree Inc., 1970:412–49.
16.
TorvikA, TorpS, LindboeCF. Atrophy of the cerebellar vermis in aging: a morphometric and histologic study. J Neurol Sci1986;76: 283–94.
17.
BertiniE, CusmaiR, deSaint BasileG, Le DeistF, diCapuaM, GaggeroDR, Dionisi-ViceC, SantilloC, CenigliaM. Congenital X-linked ataxia, progressive myoclonic encephalopathy, macular degeneration and recurrent infections. Am J Med Gen1992;43:443–51.
18.
CampanellaG, FillaA, deMicheleG. Classifications of hereditary ataxias. A critical overview. Acta Neurol1992;14:408–19.
19.
HadjivassiliouM, GrunewaldRA, ChattopadhyayAK, Davies-JonesGAB, GibsonA, JarrattJA, KandlerRH, LoboA, PowellT, SmithCML. Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia. Lancet1998;352:1582–5.
20.
ItoH, SayamaS, KanazawaN, SaitoT, KowaH, HagaS, IkedaK. Antineuronal antibodies in acute cerebellar ataxia following Epstein-Barr virus infection. Neurology1994;44:1506–7.
FleischerG, HenryW, McSorleyM, ArbeterA, PlotkinS. Life-threatening complications of varicella. Am J Dis Child1981;135: 896–9.
23.
SriramS, SteinmanL. Postinfectious and postvaccinial encephalomyelitis. Neurol Clinics1984;2:341–53.
24.
ReillyK, Cohen-SobelE, CaselliM. Ataxic gait. Complication of chicken pox. J Am Ped Med Assoc1993;83:161.
25.
ShojiH, HiraiS, IshakawaK, AramakiM, SatoY, AbeT, KojimaK. CT and MR imaging of acute cerebellar ataxia. Neuroradiology1991;33:360–1.
26.
de SilvaHJ, HoangP, DaltonH, de SilvaR, JewellDP, PieriesJB. Immune activation during cerebellar dysfunction following Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg1992;86:129–31.
27.
AufrichtCA, TennerW, StiglbauerR, RosenmayrF. Transient cerebellopontine demyelination revealed by MRI in acute cerebellar ataxia. Pediatr Radiol1990;20:602–3.
28.
GroenRJM, BegeerJH, WilminkJT, le CoultreR. Acute cerebellar ataxia in a child with transient pontine lesions demonstrated by MRI. Neuropediatrics1991;22:225–7.
DarnellRB. The importance of defining the paraneoplastic neurologic disorders. N Engl J Med1999;340:1831–3.
31.
BrainL, WilkinsonM. Subacute cerebellar degeneration associated with neoplasm. Brain1965;88:465–78.
32.
AndersonNE, RosenblumMK, PosnerJB. Paraneoplastic cerebellar degeneration: clinical-immunological correlations. Ann Neurol1988;24:559–67.
33.
PosnerJ. Paraneoplastic cerebellar degeneration. Can J Neurol Sci1993;20:S117–S122.
34.
HorwichMS, ChoL, PorroRS, PosnerJB. Subacute sensory neuropathy: a remote effect of cancer. Ann Neurol1977;2:7–19.
35.
DalmauJ, FurneauxHM, GrallaRJ, KrisMG, PosnerJB. Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer a quantitative western blot analysis. Ann Neurol1990;27: 544–52.
AndersonNE, RosenblumMK, GrausF, WileyRG, PosnerJB. Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neurology1988;38:1391–8.
38.
GrausF, ElkonKB, PosnerJB. Sensory neuropathy and small cell lung cancer. Antineuronal antibody that also react with the tumor. Am J Med1986;80:45–52.
39.
VoltzR, GultekinSH, RosenfeldMR, GerstnerE, EichenJ, PosnerJB, DalmauJ. A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N Engl J Med1999:340:1788–95.
40.
BuckanovichRJ, PosnerJB, DarnellRB. Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system. Neuron1993;11: 657–72.
41.
BuckanovichRJ, YangYYL, DarnellRB. The onconeural antigen Nova-1 is a neuron-specific RNA-binding protein, the activity of which is inhibited by paraneoplastic antibodies. J Neurosci1996;16: 1114–22.
42.
WestendorfJM, RaoPN, GeraceL. Cloning of cDNAs for M-phase phosphoproteins recognized by the MPM2 monoclonal antibody and determination of the phosphorylated epitope. Proc Natl Acad Sci USA1994;91:714–8.
43.
FritzlerMJ, PaulsJD, KinsellaTD, BowenTJ. Antinuclear, anticytoplasmic and anti-Sjögren's syndrome antigen-A (SS-A/Ro) antibodies in female blood donors. Clin Immunol Immunopathol1985;36: 120–8.
44.
FritzlerMJ, HamelJC, OchsRL, ChanEKL. Molecular characterization of two human autoantigens: unique cDNAs encoding 95- and 160-kD proteins of a putative family in the Golgi complex. J Exp Med1993;178:49–62.
45.
BonnerJ, DahmusME, FambroughDM, HuangRC, MarushigeK, TuanDHY. The biology of isolated chromatin. Science1968;159: 47–56.
46.
AdamSA, NakagawaT, SwansonMS, WoodruffTK, DreyfussG. mRNA polyadenylate binding protein: gene isolation and sequencing and identification of a ribonucleoprotein consensus sequence. Mol Cell Biol1986;6:2932–43.
47.
DevereuxJ, HaeberliP, SmithiesO. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res1984;12: 387–95.
LupasA, Van DykeM, StockJ. Predicting coiled coils from protein sequences. Science1991;252:1162–4.
50.
BergerB, WilsonD, WolfE, TonchevT, MillaM, KimP. Predicting coiled coils by use of pairwise residue correlations. Proc Natl Acad Sci USA1995;92:8259–63.
51.
SakaiK, MitchellDJ, TsukamotoT, SteinmanL. Isolation of a complementary DNA clone encoding an autoantigen recognized by an anti-neuronal cell antibody from a patient with paraneoplastic cerebellar degeneration. Ann Neurol1990;28:692–8.
52.
YenTJ, LiG, SchaarBT, SzilakI, ClevelandDW. CENP-E is a putative kinetochore motor that accumulates just before mitosis. Nature1992;359:536–9.
53.
KiersL, AltermattHJ, LennonVA. Paraneoplastic anti-neuronal nuclear IgG autoatnibodies (Type I) localize antigen in small cell lung carcinoma. Mayo Clin Proc1991;66:1209–16.
DavisFM, RaoPN. Antibodies to mitosis-specific phosphoproteins. In: SchlegelRA, ed. Molecular regulation of nuclear events in mitosis and meiosis. New York: Academic Press, 1987:259.
VandreDD, DavisFM, RaoPN, BorisyGG. Phosphoproteins are components of mitotic microtubule organizing centers. Proc Natl Acad Sci USA1984;81:4439–43.
58.
ZhaoL, KuangJ, AdlakhaRC, RaoPN. Threonine phosphorylation is associated with mitosis in HeLa cells. FEBS Lett1989;249: 389–95.
59.
WestendorfJM, KonstantinovKN, WormsleyS, ShuM-D, Matsumoto-TaniuraN, PriolletF, KlierFG, GeraceL, BasergaSJ. M phase phosphoprotein 10 is a human U3 small nucleolar ribonucleoprotein component. Mol Biol Cell1998;9:437–49.
60.
Matsumoto-TaniuraN, MonroeR, GeraceL, WestendorfJM. Identification of novel M phase phosphoproteins by expression cloning. Mol Biol Cell1996;7:1455–69.
61.
EngleDB, DoonanJH, MorrisNR. Cell-cycle modulation of MPM-2 specific spindle pole body phosphorylation in Aspergillus nidulans. Cell Motil Cytoskeleton1988;10:432–7.
62.
KuangJ, AshornCL, Gonzales-KuyvenhovenM, PenkalaJE. cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor. Mol Biol Cell1994;5:135–45.
63.
VandreDD, CentonzeVE, PeloquinJ, TombesRM, BorisyGG. Proteins of the mammalian mitotic spindle: phosphorylation/dephosphorylation of MAP-4 during mitosis. J Cell Sci1991;98:577–88.
64.
TaageperaS, RaoPN, DrakeFH, GorbskyGJ. DNA topoisomerase IIa is the major chromosome protein recognized by the mitotic phosphoprotein antibody MPM-2. Proc Natl Acad Sci USA1993;90: 8407–11.
65.
KuangJ, PenkalaJE, WrightDA, SaundersGF, RaoPN. A novel M phase-specific H1 kinase recognized by the mitosis-specific monoclonal antibody MPM-2. Devel Biol1991;144:54–64.
66.
ChanEKL, FritzlerMJ. Autoantibodies to Golgi apparatus antigens. In: ConradK, HumbelR-L, MeurerM, ShoenfeldY, TanEM, eds. Pathogenic and diagnostic relevance of autoantibodies. Proceedings 4th Dresden symposium on autoantibodies. Scottsdale, Ariz: Pabst Scientific Publishers, 1998:85–100.
67.
ChanEKL, HamelJC, BuyonJP, TanEM. Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro autoantigen. J Clin Invest1991;87:68–76.
68.
YangCH, LambieEJ, SnyderM. NuMA. An unusually long coiled-coil related protein in the mammalian nucleus. J Cell Biol1992; 116:1303–17.
69.
YanevaM, WenJ, AyalaA, CookR. cDNA-derived amino acid sequence of the 86-kDa subunit of the Ku antigen. J Biol Chem1989; 264:13407–11.
70.
ChouC-H, ReevesWH. Recognition of multiple epitopes in the coiled-coil domain of lamin B by human autoantibodies. Mol Immunol1992;29:1055–64.
71.
PollardKM, ChanEKL, GrantBJ, SullivanKF, TanEM, GlassCA. In vitro posttranslational modification of lamin B cloned from a human T-cell line. Mol Cell Biol1990;10:2164–75.
72.
CunninghamMW, AntoneSM, GuliziaJM, McManusBA, GaunttCJ. a-helical coiled-coil molecules: a role in autoimmunity against the heart. Clin Immunol Immunopathol1993;68:118–23.
73.
McCormackJM, CrossleyCA, AyoubEM, HarleyJB, CunninghamMW. Poststreptococcal anti-myosin antibody idiotype associated with systemic lupus erythematosus and Sjogren's syndrome. J Infect Dis1993;168:915–21.
74.
LiaoH, WinkfeinRJ, MackG, RattnerJB, YenTJ. CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. J Cell Biol1995;130: 507–18.
75.
SelakS, ScheonrothL, SenecalJ-L, FritzlerMJ. Early endosome antigen 1: an autoantigen associated with neurological diseases. J Investig Med1999;47:311–8.
76.
LandschulzWH, JohnsonPF, McKnightSL. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science1988;240:1759–64.
ReyneirMO, HashiehIA, CrotteC, CarbucciaN, RichardB, GerolamiA. Monensin action on the Golgi complex in perfused rat liver: evidence against bile salt vesicular transport. Gastroenterology1992;102: 2024–32.
80.
AbelT, ManiatisT. Action of leucine zippers. Nature1989;341: 24–5.
81.
LandschulzWH, JohnsonPF, AdashiE, GravesBJ, McKnightSL. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev1988;2:786–800.
82.
BucklandR, MalvoisinE, BeauvergerP, WildF. A leucine zipper structure present in the measles virus fusion protein is not required for its tetramerization but is essential for fusion. J Gen Virol1992;73: 1703–7.
83.
DelwartE, MosialosG. Retroviral envelope glycoproteins contain a leucine zipper-like retreat. AIDS Res Human Retroviruses1990; 6:703–6.
84.
TuckerS, SrinivasR, CopmansR. Molecular domains involved in oligomerization of the Friend leukemia virus envelope protein. Virology1991;16:2431–44.
85.
ChanEKL, AndradeLEC. Antinuclear antibodies in Sjögren's syndrome. Rheum Dis Clin North Am1992;18:551–70.
86.
LandbergG, TanEM, RoosG. Flow cytometric multiparameter analysis of proliferating cell nuclear antigen/cyclin and Ki-67 antigen: a new view of the cell cycle. Exp Cell Res1990;187:111–8.
87.
BrashearRH, GreenleeJE, JaeckleKA. Anticerebellar antibodies in neurologically normal patients with ovarian neoplasms. Neurology1989;39:1605–9.
