Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 May 14;93(10):4529–4536. doi: 10.1073/pnas.93.10.4529

Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain.

R B Darnell 1
PMCID: PMC39311  PMID: 8643438

Abstract

Paraneoplastic neurologic disorders (PNDs) are believed to be autoimmune neuronal degenerations that develop in some patients with systemic cancer. A series of genes encoding previously undiscovered neuronal proteins have been cloned using antiserum from PND patients. Identification of these onconeural antigens suggests a reclassification of the disorders into four groups: those in which neuromuscular junction proteins, nerve terminal/vesicle-associated proteins, neuronal RNA binding proteins, or neuronal signal-transduction proteins serve as target antigens. This review considers insights into basic neurobiology, tumor immunology, and autoimmune neuronal degeneration offered by the characterization of the onconeural antigens.

Full text

PDF
4529

Images in this article

4530Fig. 1
on p.4530

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amara S. G., Jonas V., Rosenfeld M. G., Ong E. S., Evans R. M. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature. 1982 Jul 15;298(5871):240–244. doi: 10.1038/298240a0. [DOI] [PubMed] [Google Scholar]
  2. Anderson N. E., Rosenblum M. K., Posner J. B. Paraneoplastic cerebellar degeneration: clinical-immunological correlations. Ann Neurol. 1988 Oct;24(4):559–567. doi: 10.1002/ana.410240413. [DOI] [PubMed] [Google Scholar]
  3. Baker B. S. Sex in flies: the splice of life. Nature. 1989 Aug 17;340(6234):521–524. doi: 10.1038/340521a0. [DOI] [PubMed] [Google Scholar]
  4. Bandziulis R. J., Swanson M. S., Dreyfuss G. RNA-binding proteins as developmental regulators. Genes Dev. 1989 Apr;3(4):431–437. doi: 10.1101/gad.3.4.431. [DOI] [PubMed] [Google Scholar]
  5. Bellgrau D., Gold D., Selawry H., Moore J., Franzusoff A., Duke R. C. A role for CD95 ligand in preventing graft rejection. Nature. 1995 Oct 19;377(6550):630–632. doi: 10.1038/377630a0. [DOI] [PubMed] [Google Scholar]
  6. Bendelac A. CD1: presenting unusual antigens to unusual T lymphocytes. Science. 1995 Jul 14;269(5221):185–186. doi: 10.1126/science.7542402. [DOI] [PubMed] [Google Scholar]
  7. Beroukhim R., Unwin N. Three-dimensional location of the main immunogenic region of the acetylcholine receptor. Neuron. 1995 Aug;15(2):323–331. doi: 10.1016/0896-6273(95)90037-3. [DOI] [PubMed] [Google Scholar]
  8. Blumenfeld A. M., Recht L. D., Chad D. A., DeGirolami U., Griffin T., Jaeckle K. A. Coexistence of Lambert-Eaton myasthenic syndrome and subacute cerebellar degeneration: differential effects of treatment. Neurology. 1991 Oct;41(10):1682–1685. doi: 10.1212/wnl.41.10.1682. [DOI] [PubMed] [Google Scholar]
  9. Borges L. F., Elliott P. J., Gill R., Iversen S. D., Iversen L. L. Selective extraction of small and large molecules from the cerebrospinal fluid by Purkinje neurons. Science. 1985 Apr 19;228(4697):346–348. doi: 10.1126/science.2580350. [DOI] [PubMed] [Google Scholar]
  10. Buckanovich R. J., Posner J. B., Darnell R. B. Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system. Neuron. 1993 Oct;11(4):657–672. doi: 10.1016/0896-6273(93)90077-5. [DOI] [PubMed] [Google Scholar]
  11. Buckanovich R. J., Yang Y. Y., Darnell R. B. The onconeural antigen Nova-1 is a neuron-specific RNA-binding protein, the activity of which is inhibited by paraneoplastic antibodies. J Neurosci. 1996 Feb 1;16(3):1114–1122. doi: 10.1523/JNEUROSCI.16-03-01114.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Budde-Steffen C., Anderson N. E., Rosenblum M. K., Graus F., Ford D., Synek B. J., Wray S. H., Posner J. B. An antineuronal autoantibody in paraneoplastic opsoclonus. Ann Neurol. 1988 May;23(5):528–531. doi: 10.1002/ana.410230518. [DOI] [PubMed] [Google Scholar]
  13. Burd C. G., Dreyfuss G. Conserved structures and diversity of functions of RNA-binding proteins. Science. 1994 Jul 29;265(5172):615–621. doi: 10.1126/science.8036511. [DOI] [PubMed] [Google Scholar]
  14. Casado J. L., Gil-Peralta A., Graus F., Arenas C., Lopez J. M., Alberca R. Anti-Ri antibodies associated with opsoclonus and progressive encephalomyelitis with rigidity. Neurology. 1994 Aug;44(8):1521–1522. doi: 10.1212/wnl.44.8.1521. [DOI] [PubMed] [Google Scholar]
  15. Casciola-Rosen L. A., Anhalt G., Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med. 1994 Apr 1;179(4):1317–1330. doi: 10.1084/jem.179.4.1317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Chen L., Ashe S., Brady W. A., Hellström I., Hellström K. E., Ledbetter J. A., McGowan P., Linsley P. S. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell. 1992 Dec 24;71(7):1093–1102. doi: 10.1016/s0092-8674(05)80059-5. [DOI] [PubMed] [Google Scholar]
  17. Christgau S., Aanstoot H. J., Schierbeck H., Begley K., Tullin S., Hejnaes K., Baekkeskov S. Membrane anchoring of the autoantigen GAD65 to microvesicles in pancreatic beta-cells by palmitoylation in the NH2-terminal domain. J Cell Biol. 1992 Jul;118(2):309–320. doi: 10.1083/jcb.118.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Couraud P. O. Interactions between lymphocytes, macrophages, and central nervous system cells. J Leukoc Biol. 1994 Sep;56(3):407–415. doi: 10.1002/jlb.56.3.407. [DOI] [PubMed] [Google Scholar]
  19. Cunningham J., Graus F., Anderson N., Posner J. B. Partial characterization of the Purkinje cell antigens in paraneoplastic cerebellar degeneration. Neurology. 1986 Sep;36(9):1163–1168. doi: 10.1212/wnl.36.9.1163. [DOI] [PubMed] [Google Scholar]
  20. Dalmau J., Furneaux H. M., Cordon-Cardo C., Posner J. B. The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues. Am J Pathol. 1992 Oct;141(4):881–886. [PMC free article] [PubMed] [Google Scholar]
  21. Dalmau J., Furneaux H. M., Gralla R. J., Kris M. G., Posner J. B. Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer--a quantitative western blot analysis. Ann Neurol. 1990 May;27(5):544–552. doi: 10.1002/ana.410270515. [DOI] [PubMed] [Google Scholar]
  22. Dalmau J., Graus F., Cheung N. K., Rosenblum M. K., Ho A., Cañete A., Delattre J. Y., Thompson S. J., Posner J. B. Major histocompatibility proteins, anti-Hu antibodies, and paraneoplastic encephalomyelitis in neuroblastoma and small cell lung cancer. Cancer. 1995 Jan 1;75(1):99–109. doi: 10.1002/1097-0142(19950101)75:1<99::aid-cncr2820750117>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  23. Dalmau J., Graus F., Rosenblum M. K., Posner J. B. Anti-Hu--associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore) 1992 Mar;71(2):59–72. doi: 10.1097/00005792-199203000-00001. [DOI] [PubMed] [Google Scholar]
  24. Dalmau J., Posner J. B. Neurologic paraneoplastic antibodies (anti-Yo; anti-Hu; anti-Ri): the case for a nomenclature based on antibody and antigen specificity. Neurology. 1994 Dec;44(12):2241–2246. doi: 10.1212/wnl.44.12.2241. [DOI] [PubMed] [Google Scholar]
  25. Darnell R. B., DeAngelis L. M. Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies. Lancet. 1993 Jan 2;341(8836):21–22. doi: 10.1016/0140-6736(93)92485-c. [DOI] [PubMed] [Google Scholar]
  26. Darnell R. B., Furneaux H. M., Posner J. B. Antiserum from a patient with cerebellar degeneration identifies a novel protein in Purkinje cells, cortical neurons, and neuroectodermal tumors. J Neurosci. 1991 May;11(5):1224–1230. doi: 10.1523/JNEUROSCI.11-05-01224.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. David C., McPherson P. S., Mundigl O., de Camilli P. A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):331–335. doi: 10.1073/pnas.93.1.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. De Camilli P., Thomas A., Cofiell R., Folli F., Lichte B., Piccolo G., Meinck H. M., Austoni M., Fassetta G., Bottazzo G. The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer. J Exp Med. 1993 Dec 1;178(6):2219–2223. doi: 10.1084/jem.178.6.2219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Elferink L. A., Peterson M. R., Scheller R. H. A role for synaptotagmin (p65) in regulated exocytosis. Cell. 1993 Jan 15;72(1):153–159. doi: 10.1016/0092-8674(93)90059-y. [DOI] [PubMed] [Google Scholar]
  30. Engebrecht J. A., Voelkel-Meiman K., Roeder G. S. Meiosis-specific RNA splicing in yeast. Cell. 1991 Sep 20;66(6):1257–1268. doi: 10.1016/0092-8674(91)90047-3. [DOI] [PubMed] [Google Scholar]
  31. Fabian R. H., Petroff G. Intraneuronal IgG in the central nervous system: uptake by retrograde axonal transport. Neurology. 1987 Nov;37(11):1780–1784. doi: 10.1212/wnl.37.11.1780. [DOI] [PubMed] [Google Scholar]
  32. Fathallah-Shaykh H., Wolf S., Wong E., Posner J. B., Furneaux H. M. Cloning of a leucine-zipper protein recognized by the sera of patients with antibody-associated paraneoplastic cerebellar degeneration. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3451–3454. doi: 10.1073/pnas.88.8.3451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Fueyo J., Gomez-Manzano C., Pascual J., Pou A. Paraneoplastic syndromes. Neurology. 1993 Jan;43(1):236–236. doi: 10.1212/wnl.43.1_part_1.236. [DOI] [PubMed] [Google Scholar]
  34. Fukunaga H., Engel A. G., Lang B., Newsom-Davis J., Vincent A. Passive transfer of Lambert-Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic membrane active zones. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7636–7640. doi: 10.1073/pnas.80.24.7636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Fukuoka T., Engel A. G., Lang B., Newsom-Davis J., Prior C., Wray D. W. Lambert-Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones. Ann Neurol. 1987 Aug;22(2):193–199. doi: 10.1002/ana.410220203. [DOI] [PubMed] [Google Scholar]
  36. Furneaux H. F., Reich L., Posner J. B. Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology. 1990 Jul;40(7):1085–1091. doi: 10.1212/wnl.40.7.1085. [DOI] [PubMed] [Google Scholar]
  37. Gao F. B., Carson C. C., Levine T., Keene J. D. Selection of a subset of mRNAs from combinatorial 3' untranslated region libraries using neuronal RNA-binding protein Hel-N1. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11207–11211. doi: 10.1073/pnas.91.23.11207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Gattenlöhner S., Brabletz T., Schultz A., Marx A., Müller-Hermelink H. K., Kirchner T. Cloning of a cDNA coding for the acetylcholine receptor alpha-subunit from a thymoma associated with myasthenia [correction of myastenia] gravis. Thymus. 1994;23(2):103–113. [PubMed] [Google Scholar]
  39. Graus F., Cordon-Cardo C., Posner J. B. Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology. 1985 Apr;35(4):538–543. doi: 10.1212/wnl.35.4.538. [DOI] [PubMed] [Google Scholar]
  40. Graus F., Elkon K. B., Cordon-Cardo C., Posner J. B. Sensory neuronopathy and small cell lung cancer. Antineuronal antibody that also reacts with the tumor. Am J Med. 1986 Jan;80(1):45–52. doi: 10.1016/0002-9343(86)90047-1. [DOI] [PubMed] [Google Scholar]
  41. Graus F., Illa I., Agusti M., Ribalta T., Cruz-Sanchez F., Juarez C. Effect of intraventricular injection of an anti-Purkinje cell antibody (anti-Yo) in a guinea pig model. J Neurol Sci. 1991 Nov;106(1):82–87. doi: 10.1016/0022-510x(91)90198-g. [DOI] [PubMed] [Google Scholar]
  42. Graus F., Rowe G., Fueyo J., Darnell R. B., Dalmau J. The neuronal nuclear antigen recognized by the human anti-Ri autoantibody is expressed in central but not peripheral nervous system neurons. Neurosci Lett. 1993 Feb 19;150(2):212–214. doi: 10.1016/0304-3940(93)90538-v. [DOI] [PubMed] [Google Scholar]
  43. Graus F., Segurado O. G., Tolosa E. Selective concentration of anti-Purkinje cell antibody in the CSF of two patients with paraneoplastic cerebellar degeneration. Acta Neurol Scand. 1988 Sep;78(3):210–213. doi: 10.1111/j.1600-0404.1988.tb03648.x. [DOI] [PubMed] [Google Scholar]
  44. Greenlee J. E., Parks T. N., Jaeckle K. A. Type IIa ('anti-Hu') antineuronal antibodies produce destruction of rat cerebellar granule neurons in vitro. Neurology. 1993 Oct;43(10):2049–2054. doi: 10.1212/wnl.43.10.2049. [DOI] [PubMed] [Google Scholar]
  45. Griffith T. S., Brunner T., Fletcher S. M., Green D. R., Ferguson T. A. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995 Nov 17;270(5239):1189–1192. doi: 10.1126/science.270.5239.1189. [DOI] [PubMed] [Google Scholar]
  46. Gumperz J. E., Parham P. The enigma of the natural killer cell. Nature. 1995 Nov 16;378(6554):245–248. doi: 10.1038/378245a0. [DOI] [PubMed] [Google Scholar]
  47. Hormigo A., Dalmau J., Rosenblum M. K., River M. E., Posner J. B. Immunological and pathological study of anti-Ri-associated encephalopathy. Ann Neurol. 1994 Dec;36(6):896–902. doi: 10.1002/ana.410360615. [DOI] [PubMed] [Google Scholar]
  48. Jaeckle K. A., Graus F., Houghton A., Cardon-Cardo C., Nielsen S. L., Posner J. B. Autoimmune response of patients with paraneoplastic cerebellar degeneration to a Purkinje cell cytoplasmic protein antigen. Ann Neurol. 1985 Nov;18(5):592–600. doi: 10.1002/ana.410180513. [DOI] [PubMed] [Google Scholar]
  49. King P. H., Levine T. D., Fremeau R. T., Jr, Keene J. D. Mammalian homologs of Drosophila ELAV localized to a neuronal subset can bind in vitro to the 3' UTR of mRNA encoding the Id transcriptional repressor. J Neurosci. 1994 Apr;14(4):1943–1952. doi: 10.1523/JNEUROSCI.14-04-01943.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Kornstein M. J., Asher O., Fuchs S. Acetylcholine receptor alpha-subunit and myogenin mRNAs in thymus and thymomas. Am J Pathol. 1995 Jun;146(6):1320–1324. [PMC free article] [PubMed] [Google Scholar]
  51. Lagnado C. A., Brown C. Y., Goodall G. J. AUUUA is not sufficient to promote poly(A) shortening and degradation of an mRNA: the functional sequence within AU-rich elements may be UUAUUUA(U/A)(U/A). Mol Cell Biol. 1994 Dec;14(12):7984–7995. doi: 10.1128/mcb.14.12.7984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Lampson L. A., Grabowska A., Whelan J. P. Class I and II MHC expression and its implications for regeneration in the nervous system. Prog Brain Res. 1994;103:307–317. doi: 10.1016/s0079-6123(08)61145-0. [DOI] [PubMed] [Google Scholar]
  53. Lang B., Newsom-Davis J., Wray D., Vincent A., Murray N. Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet. 1981 Aug 1;2(8240):224–226. doi: 10.1016/s0140-6736(81)90474-8. [DOI] [PubMed] [Google Scholar]
  54. Lem J., Flannery J. G., Li T., Applebury M. L., Farber D. B., Simon M. I. Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase beta subunit. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4422–4426. doi: 10.1073/pnas.89.10.4422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Lennon V. A., Kryzer T. J., Griesmann G. E., O'Suilleabhain P. E., Windebank A. J., Woppmann A., Miljanich G. P., Lambert E. H. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med. 1995 Jun 1;332(22):1467–1474. doi: 10.1056/NEJM199506013322203. [DOI] [PubMed] [Google Scholar]
  56. Leveque C., Hoshino T., David P., Shoji-Kasai Y., Leys K., Omori A., Lang B., el Far O., Sato K., Martin-Moutot N. The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative Lambert-Eaton myasthenic syndrome antigen. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3625–3629. doi: 10.1073/pnas.89.8.3625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Levine B., Hardwick J. M., Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. Antibody-mediated clearance of alphavirus infection from neurons. Science. 1991 Nov 8;254(5033):856–860. doi: 10.1126/science.1658936. [DOI] [PubMed] [Google Scholar]
  58. Levine T. D., Gao F., King P. H., Andrews L. G., Keene J. D. Hel-N1: an autoimmune RNA-binding protein with specificity for 3' uridylate-rich untranslated regions of growth factor mRNAs. Mol Cell Biol. 1993 Jun;13(6):3494–3504. doi: 10.1128/mcb.13.6.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Luque F. A., Furneaux H. M., Ferziger R., Rosenblum M. K., Wray S. H., Schold S. C., Jr, Glantz M. J., Jaeckle K. A., Biran H., Lesser M. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol. 1991 Mar;29(3):241–251. doi: 10.1002/ana.410290303. [DOI] [PubMed] [Google Scholar]
  60. Manley G. T., Smitt P. S., Dalmau J., Posner J. B. Hu antigens: reactivity with Hu antibodies, tumor expression, and major immunogenic sites. Ann Neurol. 1995 Jul;38(1):102–110. doi: 10.1002/ana.410380117. [DOI] [PubMed] [Google Scholar]
  61. Martin-Moutot N., el Far O., Leveque C., David P., Marqueze B., Lang B., Newsom-Davis J., Hoshino T., Takahashi M., Seagar M. J. Synaptotagmin: a Lambert-Eaton myasthenic syndrome antigen that associates with presynaptic calcium channels. J Physiol Paris. 1993;87(1):37–41. doi: 10.1016/0928-4257(93)90022-l. [DOI] [PubMed] [Google Scholar]
  62. McCullough A. J., Schuler M. A. AU-rich intronic elements affect pre-mRNA 5' splice site selection in Drosophila melanogaster. Mol Cell Biol. 1993 Dec;13(12):7689–7697. doi: 10.1128/mcb.13.12.7689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Motomura M., Johnston I., Lang B., Vincent A., Newsom-Davis J. An improved diagnostic assay for Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry. 1995 Jan;58(1):85–87. doi: 10.1136/jnnp.58.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Neumann H., Cavalié A., Jenne D. E., Wekerle H. Induction of MHC class I genes in neurons. Science. 1995 Jul 28;269(5223):549–552. doi: 10.1126/science.7624779. [DOI] [PubMed] [Google Scholar]
  65. Newman L. S., McKeever M. O., Okano H. J., Darnell R. B. Beta-NAP, a cerebellar degeneration antigen, is a neuron-specific vesicle coat protein. Cell. 1995 Sep 8;82(5):773–783. doi: 10.1016/0092-8674(95)90474-3. [DOI] [PubMed] [Google Scholar]
  66. Newsom-Davis J., Murray N. M. Plasma exchange and immunosuppressive drug treatment in the Lambert-Eaton myasthenic syndrome. Neurology. 1984 Apr;34(4):480–485. doi: 10.1212/wnl.34.4.480. [DOI] [PubMed] [Google Scholar]
  67. Newsom-Davis J., Vincent A., Wilson S. G., Ward C. D., Pinching A. J., Hawkey C. [Plasmapheresis for myasthenia gravis]. N Engl J Med. 1978 Feb 23;298(8):456–457. [PubMed] [Google Scholar]
  68. Peterson K., Rosenblum M. K., Kotanides H., Posner J. B. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology. 1992 Oct;42(10):1931–1937. doi: 10.1212/wnl.42.10.1931. [DOI] [PubMed] [Google Scholar]
  69. Polans A. S., Buczyłko J., Crabb J., Palczewski K. A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy. J Cell Biol. 1991 Mar;112(5):981–989. doi: 10.1083/jcb.112.5.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Porcelli S. A., Modlin R. L. CD1 and the expanding universe of T cell antigens. J Immunol. 1995 Oct 15;155(8):3709–3710. [PubMed] [Google Scholar]
  71. Posner J. B. Anti-Hu autoantibody associated sensory neuropathy/encephalomyelitis: a model of paraneoplastic syndrome. Perspect Biol Med. 1995 Winter;38(2):167–181. doi: 10.1353/pbm.1995.0043. [DOI] [PubMed] [Google Scholar]
  72. Rall G. F., Mucke L., Oldstone M. B. Consequences of cytotoxic T lymphocyte interaction with major histocompatibility complex class I-expressing neurons in vivo. J Exp Med. 1995 Nov 1;182(5):1201–1212. doi: 10.1084/jem.182.5.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Roberts A., Perera S., Lang B., Vincent A., Newsom-Davis J. Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line. Nature. 1985 Oct 24;317(6039):737–739. doi: 10.1038/317737a0. [DOI] [PubMed] [Google Scholar]
  74. Robinow S., Campos A. R., Yao K. M., White K. The elav gene product of Drosophila, required in neurons, has three RNP consensus motifs. Science. 1988 Dec 16;242(4885):1570–1572. doi: 10.1126/science.3144044. [DOI] [PubMed] [Google Scholar]
  75. Rosenfeld M. G., Mermod J. J., Amara S. G., Swanson L. W., Sawchenko P. E., Rivier J., Vale W. W., Evans R. M. Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature. 1983 Jul 14;304(5922):129–135. doi: 10.1038/304129a0. [DOI] [PubMed] [Google Scholar]
  76. Rosenfeld M. R., Wong E., Dalmau J., Manley G., Posner J. B., Sher E., Furneaux H. M. Cloning and characterization of a Lambert-Eaton myasthenic syndrome antigen. Ann Neurol. 1993 Jan;33(1):113–120. doi: 10.1002/ana.410330126. [DOI] [PubMed] [Google Scholar]
  77. Sakai K., Gofuku M., Kitagawa Y., Ogasawara T., Hirose G. Induction of anti-Purkinje cell antibodies in vivo by immunizing with a recombinant 52-kDa paraneoplastic cerebellar degeneration-associated protein. J Neuroimmunol. 1995 Jul;60(1-2):135–141. doi: 10.1016/0165-5728(95)00063-8. [DOI] [PubMed] [Google Scholar]
  78. Sakai K., Gofuku M., Kitagawa Y., Ogasawara T., Hirose G., Yamazaki M., Koh C. S., Yanagisawa N., Steinman L. A hippocampal protein associated with paraneoplastic neurologic syndrome and small cell lung carcinoma. Biochem Biophys Res Commun. 1994 Mar 30;199(3):1200–1208. doi: 10.1006/bbrc.1994.1358. [DOI] [PubMed] [Google Scholar]
  79. Sakai K., Mitchell D. J., Tsukamoto T., Steinman L. Isolation of a complementary DNA clone encoding an autoantigen recognized by an anti-neuronal cell antibody from a patient with paraneoplastic cerebellar degeneration. Ann Neurol. 1990 Nov;28(5):692–698. doi: 10.1002/ana.410280515. [DOI] [PubMed] [Google Scholar]
  80. Sakai K., Ogasawara T., Hirose G., Jaeckle K. A., Greenlee J. E. Analysis of autoantibody binding to 52-kd paraneoplastic cerebellar degeneration-associated antigen expressed in recombinant proteins. Ann Neurol. 1993 Apr;33(4):373–380. doi: 10.1002/ana.410330407. [DOI] [PubMed] [Google Scholar]
  81. Siebel C. W., Admon A., Rio D. C. Soma-specific expression and cloning of PSI, a negative regulator of P element pre-mRNA splicing. Genes Dev. 1995 Feb 1;9(3):269–283. doi: 10.1101/gad.9.3.269. [DOI] [PubMed] [Google Scholar]
  82. Sillevis Smitt P. A., Manley G. T., Posner J. B. Immunization with the paraneoplastic encephalomyelitis antigen HuD does not cause neurologic disease in mice. Neurology. 1995 Oct;45(10):1873–1878. doi: 10.1212/wnl.45.10.1873. [DOI] [PubMed] [Google Scholar]
  83. Siomi H., Siomi M. C., Nussbaum R. L., Dreyfuss G. The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein. Cell. 1993 Jul 30;74(2):291–298. doi: 10.1016/0092-8674(93)90420-u. [DOI] [PubMed] [Google Scholar]
  84. Smith D. P., Ranganathan R., Hardy R. W., Marx J., Tsuchida T., Zuker C. S. Photoreceptor deactivation and retinal degeneration mediated by a photoreceptor-specific protein kinase C. Science. 1991 Dec 6;254(5037):1478–1484. doi: 10.1126/science.1962207. [DOI] [PubMed] [Google Scholar]
  85. Solimena M., Folli F., Denis-Donini S., Comi G. C., Pozza G., De Camilli P., Vicari A. M. Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N Engl J Med. 1988 Apr 21;318(16):1012–1020. doi: 10.1056/NEJM198804213181602. [DOI] [PubMed] [Google Scholar]
  86. Szabo A., Dalmau J., Manley G., Rosenfeld M., Wong E., Henson J., Posner J. B., Furneaux H. M. HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. Cell. 1991 Oct 18;67(2):325–333. doi: 10.1016/0092-8674(91)90184-z. [DOI] [PubMed] [Google Scholar]
  87. Tan E. M. Autoantibodies in pathology and cell biology. Cell. 1991 Nov 29;67(5):841–842. doi: 10.1016/0092-8674(91)90356-4. [DOI] [PubMed] [Google Scholar]
  88. Tan E. M. Autoimmunity and apoptosis. J Exp Med. 1994 Apr 1;179(4):1083–1086. doi: 10.1084/jem.179.4.1083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Thirkill C. E., FitzGerald P., Sergott R. C., Roth A. M., Tyler N. K., Keltner J. L. Cancer-associated retinopathy (CAR syndrome) with antibodies reacting with retinal, optic-nerve, and cancer cells. N Engl J Med. 1989 Dec 7;321(23):1589–1594. doi: 10.1056/NEJM198912073212307. [DOI] [PubMed] [Google Scholar]
  90. Thirkill C. E., Tait R. C., Tyler N. K., Roth A. M., Keltner J. L. The cancer-associated retinopathy antigen is a recoverin-like protein. Invest Ophthalmol Vis Sci. 1992 Sep;33(10):2768–2772. [PubMed] [Google Scholar]
  91. Toyka K. V., Brachman D. B., Pestronk A., Kao I. Myasthenia gravis: passive transfer from man to mouse. Science. 1975 Oct 24;190(4212):397–399. doi: 10.1126/science.1179220. [DOI] [PubMed] [Google Scholar]
  92. Tzartos S. J., Lindstrom J. M. Monoclonal antibodies used to probe acetylcholine receptor structure: localization of the main immunogenic region and detection of similarities between subunits. Proc Natl Acad Sci U S A. 1980 Feb;77(2):755–759. doi: 10.1073/pnas.77.2.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Valcárcel J., Singh R., Zamore P. D., Green M. R. The protein Sex-lethal antagonizes the splicing factor U2AF to regulate alternative splicing of transformer pre-mRNA. Nature. 1993 Mar 11;362(6416):171–175. doi: 10.1038/362171a0. [DOI] [PubMed] [Google Scholar]
  94. Wang L. H., Südhof T. C., Anderson R. G. The appendage domain of alpha-adaptin is a high affinity binding site for dynamin. J Biol Chem. 1995 Apr 28;270(17):10079–10083. doi: 10.1074/jbc.270.17.10079. [DOI] [PubMed] [Google Scholar]
  95. Williams K. C., Hickey W. F. Traffic of hematogenous cells through the central nervous system. Curr Top Microbiol Immunol. 1995;202:221–245. doi: 10.1007/978-3-642-79657-9_15. [DOI] [PubMed] [Google Scholar]
  96. Wucherpfennig K. W. Autoimmunity in the central nervous system: mechanisms of antigen presentation and recognition. Clin Immunol Immunopathol. 1994 Sep;72(3):293–306. doi: 10.1006/clin.1994.1145. [DOI] [PubMed] [Google Scholar]
  97. Yao K. M., Samson M. L., Reeves R., White K. Gene elav of Drosophila melanogaster: a prototype for neuronal-specific RNA binding protein gene family that is conserved in flies and humans. J Neurobiol. 1993 Jun;24(6):723–739. doi: 10.1002/neu.480240604. [DOI] [PubMed] [Google Scholar]
  98. Zaheer W., Friedland M. L., Cooper E. B., DoRosario A., Burd R. M., Gagliardi J., Torstenson G. Spontaneous regression of small cell carcinoma of lung associated with severe neuropathy. Cancer Invest. 1993;11(3):306–309. doi: 10.3109/07357909309024856. [DOI] [PubMed] [Google Scholar]
  99. Zubiaga A. M., Belasco J. G., Greenberg M. E. The nonamer UUAUUUAUU is the key AU-rich sequence motif that mediates mRNA degradation. Mol Cell Biol. 1995 Apr;15(4):2219–2230. doi: 10.1128/mcb.15.4.2219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. van der Bruggen P., Traversari C., Chomez P., Lurquin C., De Plaen E., Van den Eynde B., Knuth A., Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991 Dec 13;254(5038):1643–1647. doi: 10.1126/science.1840703. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES