title: Protein kinase Cgamma autoimmunity in paraneoplastic cerebellar degeneration and non-small-cell lung cancer.
abstract: BACKGROUND
  The clinical and immunological profiles of patients with paraneoplastic cerebellar degeneration (PCD) and non-small-cell lung cancer (NSCLC) are not well known.
  
  
  OBJECTIVE
  To review the clinical and immunological features of patients with PCD, NSCLC and without well-characterised onconeural antibodies.
  
  
  METHODS
  The clinical features of nine patients with the diagnosis of classical PCD and NSCLC, included in our archives, were retrospectively reviewed. The presence of antibodies to cerebellar components was determined by immunohistochemistry and immunoblot of rat cerebellum. A cDNA library of human cerebellum was screened with the positive sera to identify the antigen.
  
  
  RESULTS
  Nine patients with PCD and NSCLC were identified. Six patients were men, and the median age at diagnosis of PCD was 63 (range 47-73) years. PCD was completely reversed in two patients, and partially in one, after treatment of the tumour. The serum of one of the patients with PCD showed a unique reactivity with Purkinje cells. The screening of a cerebellar-expression library resulted in the isolation of protein kinase Cgamma (PKCgamma). PKCgamma immunoreactivity was not observed in the serum of 170 patients with non-paraneoplastic neurological syndromes, 27 patients with PCD, no onconeural antibodies and small-cell lung cancer, and 52 patients with NSCLC without paraneoplastic neurological syndromes. The NSCLC from 11 patients without PCD did not express PKCgamma at either the RNA or protein level. However, many cells of the NSCLC of the patient with PKCgamma antibodies expressed PKCgamma.
  
  
  CONCLUSIONS
  PCD occurs in patients with NSCLC without typical onconeural antibodies and is associated with immune reactions against key proteins of the Purkinje cells.
authors.affiliation: Service of Neurology, Hospital Clinic, and Institut d' Investigació Biomèdica August Pi i Sunyer, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Sabater
authors.forename: L
authors.initials: L
authors.lastname: Bataller
authors.forename: A F
authors.initials: AF
authors.lastname: Carpentier
authors.forename: M L
authors.initials: ML
authors.lastname: Aguirre-Cruz
authors.forename: A
authors.initials: A
authors.lastname: Saiz
authors.forename: B
authors.initials: B
authors.lastname: Benyahia
authors.forename: J
authors.initials: J
authors.lastname: Dalmau
authors.forename: F
authors.initials: F
authors.lastname: Graus
mesh_terms: D000368:Aged; D000906:Antibodies / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020362:Paraneoplastic Cerebellar Degeneration / Q000276:immunology*; D011493:Protein Kinase C / Q000032:analysis / Q000276:immunology*; D011689:Purkinje Cells / Q000276:immunology; D012189:Retrospective Studies
chemical_list: D000906:Antibodies; C087857:protein kinase C gamma; D011493:Protein Kinase C