title: Early endosome antigen. 1: An autoantigen associated with neurological diseases.
abstract: BACKGROUND
  We have identified 36 human sera sent for autoantibody analyses that produce a unique vesicular staining pattern of the cytoplasm of tissue culture cells. The purpose of this study was to identify the autoantigens that are recognized by the sera that produce this staining pattern and determine if the patients have common clinical features.
  
  
  METHODS
  A serum from one of the patients (MS) with rapidly progressive demyelinating polyneuropathy was used to isolate a approximately 4.5 kb cDNA insert from a HeLa expression library. The purified cDNA (MS-5.1) was characterized by a poly A tail and an open reading frame that encoded 1329 amino acids. The derived amino acid sequence was found to be 99% identical to a 180 kd peripheral endosomal protein named early endosome antigen (EEA1).
  
  
  RESULTS
  Antibodies from rabbits immunized with the recombinant protein and the prototype human serum produced an identical distinctive speckled cytoplasmic staining pattern. These sera also precipitated the in vitro translated recombinant protein and reacted with the isolated recombinant protein in a Western immunoblot. Of the 36 sera that produced an identical staining pattern as the prototype and immune rabbit sera, 8 (22%) had IgG antibodies that recognized the recombinant EEA1 protein when tested by immunoblotting and immunoprecipitation assays. Of the 8 patients with anti-EEA1 antibodies 4 were females, 4 were males, and the mean age was 69 years (range 48 to 86 years).
  
  
  CONCLUSIONS
  Diagnoses included: polyneuropathy, lower motor neuron disease, pigmented retinitis, seronegative polyarthritis, interstitial pulmonary fibrosis, Raynaud's phenomenon, Wegener's granulomatosis, and proteinuria. Three of the eight patients with EEA1 autoantibodies died within 1 year after EEA1 antibodies were identified.
authors.affiliation: Faculty of Medicine, Calgary, AB Canada.
authors.forename: S
authors.initials: S
authors.lastname: Selak
authors.forename: E K
authors.initials: EK
authors.lastname: Chan
authors.forename: L
authors.initials: L
authors.lastname: Schoenroth
authors.forename: J L
authors.initials: JL
authors.lastname: Senécal
authors.forename: M J
authors.initials: MJ
authors.lastname: Fritzler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D018076:DNA, Complementary / Q000235:genetics; D003711:Demyelinating Diseases / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D011817:Rabbits; D033921:Vesicular Transport Proteins
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018076:DNA, Complementary; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1