title: High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome.
abstract: OBJECTIVE
  To elucidate the humoral immune response in patients with chronic fatigue syndrome (CFS), by identification and characterization of autoantibodies.
  
  
  METHODS
  Initial immunofluorescence histochemistry studies of sera using human HEp-2 cell substrate were followed by antibody class subtyping and colocalization studies with reference antibodies. Association of CFS autoantigens with insoluble cellular components was determined by in situ extraction of soluble components and subsequent immunofluorescence histochemistry studies on the extracted cell substrate.
  
  
  RESULTS
  Of 60 CFS patients, 41 (68%) were positive for antinuclear antibodies. Localization of nuclear staining was found at the nuclear envelope (52%), in reticulated speckles (25%), in nucleoli (13%), and in dense fine speckles (5%). Twenty-eight CFS sera (47%) also had antibodies to cytoplasmic antigens. The major cytoplasmic staining pattern was of the intermediate filament type (35%). The observed nuclear envelope pattern of staining co-localized with lamina-associated polypeptide 2 (an integral nuclear membrane protein), the reticulated speckle pattern co-localized with non-small nuclear RNP splicing factor SC-35, and the intermediate filament pattern co-localized with vimentin. The intermediate filament antigen was shown to be vimentin in immunoblotting experiments using recombinant human vimentin, and one of the nuclear envelope antigens was shown previously to be lamin B1. Fifty of the 60 CFS patients (83%) had antibodies to one or another of these antigens, all of which are relatively insoluble cellular antigens, whereas a control group of patients without chronic fatigue had a significantly lower frequency of such antibodies (17%).
  
  
  CONCLUSIONS
  The high frequency of autoantibodies to insoluble cellular antigens in CFS represents a unique feature which might help to distinguish CFS from other rheumatic autoimmune diseases.
authors.affiliation: Institut fur Umwelthygiene, Heinrich Heine Universitat Dusseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: von Mikecz
authors.forename: K
authors.initials: K
authors.lastname: Konstantinov
authors.forename: D S
authors.initials: DS
authors.lastname: Buchwald
authors.forename: L
authors.initials: L
authors.lastname: Gerace
authors.forename: E M
authors.initials: EM
authors.lastname: Tan
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D003429:Cross Reactions; D003598:Cytoskeletal Proteins / Q000276:immunology; D018076:DNA, Complementary / Q000032:analysis; D015673:Fatigue Syndrome, Chronic / Q000097:blood*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015151:Immunoblotting; D009687:Nuclear Proteins / Q000276:immunology; D012995:Solubility; D014746:Vimentin / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D009687:Nuclear Proteins; D014746:Vimentin