title: Autoantibodies against granulocyte colony-stimulating factor in Felty's syndrome and neutropenic systemic lupus erythematosus.
abstract: OBJECTIVE
  Cytokines and growth factors can be a target of autoantibodies in systemic inflammatory diseases. We examined whether patients with neutropenia and either Felty's syndrome (FS) or systemic lupus erythematosus (SLE) have autoantibodies against granulocyte colony-stimulating factor (G-CSF) and whether these autoantibodies are functionally relevant.
  
  
  METHODS
  Fifteen patients with neutropenia due to FS were matched for age, sex, and disease activity with 16 normocytic rheumatoid arthritis (RA) control patients. Sixteen patients with SLE and neutropenia were matched with 16 normocytic SLE control patients. Antibodies against G-CSF were measured by enzyme-linked immunosorbent assay and Western blotting. Antibody specificity was verified by competitive inhibition using recombinant human G-CSF. The effect of anti-G-CSF antibodies on the functional activity of their target molecule was measured in a bioassay using G-CSF-sensitive murine 32D cells.
  
  
  RESULTS
  IgG anti-G-CSF was found in 11 FS patients, 6 SLE patients with neutropenia, 6 SLE control patients, and none of the RA control patients. IgM anti-G-CSF was found in 6 neutropenic and 3 normocytic SLE patients. Anti-G-CSF antibodies were associated with an exaggerated serum level of G-CSF and a low neutrophil count. A neutralizing effect of anti-G-CSF antibodies on its target molecule was found in 3 of the 9 patients tested. Irrespective of the presence or absence of anti-G-CSF antibodies, neutropenic patients with FS and SLE had exaggerated serum levels of G-CSF.
  
  
  CONCLUSIONS
  Anti-G-CSF autoantibodies are common in neutropenia due to FS and SLE. In individual patients, these autoantibodies have a neutralizing capacity. In patients without neutralizing antibodies, hyposensitivity of the myeloid cells to G-CSF appears to be central to the pathogenesis of the neutropenia in FS and SLE.
mesh_terms: D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D001681:Biological Assay; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005258:Felty Syndrome / Q000150:complications / Q000276:immunology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D016179:Granulocyte Colony-Stimulating Factor