title: High titer autoantibodies to GM-CSF in patients with AML, CML and MDS are associated with active disease.
abstract: Antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can be induced when GM-CSF is used as an adjuvant to solid tumor vaccination. Neutralizing anti-GM-CSF IgG has been associated with pulmonary alveolar proteinosis (PAP), and secondary PAP has been linked to myeloid leukemia. We studied 69 patients with acute myeloid leukemia, chronic myeloid leukemia and myelodysplastic syndrome, including 19 patients who received GM-CSF with peptide antigen and incomplete Freund's adjuvant in a vaccine trial for the presence or induction of anti-GM-CSF antibodies. Anti-GM-CSF IgG were present in 36 (52%) patients with myeloid leukemia compared to only 1 of 33 (3%) healthy subjects (P=0.008) and in none of 6 patients with lymphoid leukemia (P=0.0001). Antibody titers were unaffected by vaccination. Anti-GM-CSF IgA and IgM were found in 33 and 20% of patients, respectively; IgA from two patients neutralized GM-CSF. Strikingly, while anti-GM-CSF IgG titers were higher in patients with active disease (n=52) versus those in complete remission (n=14, P=0.0009), GM-CSF expression was not increased in either group. These data are first to show that anti-GM-CSF antibodies of multiple isotypes are present in patients with active myeloid leukemia without PAP and may be useful markers of disease activity.
authors.affiliation: Section of Transplantation Immunology, Department of Stem Cell Transplantation and Cell Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sergeeva
authors.forename: Y
authors.initials: Y
authors.lastname: Ono
authors.forename: R
authors.initials: R
authors.lastname: Rios
authors.forename: J J
authors.initials: JJ
authors.lastname: Molldrem
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D019496:Cancer Vaccines / Q000276:immunology; D016022:Case-Control Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000276:immunology; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000276:immunology; D014611:Vaccination
chemical_list: D001323:Autoantibodies; D019496:Cancer Vaccines; D007132:Immunoglobulin Isotypes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor