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Immunology

High titer autoantibodies to GM-CSF in patients with AML, CML and MDS are associated with active disease

Leukemia volume 22, pages 783–790 (2008)Cite this article

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.

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Acknowledgements

We thank Maria Tanguma for the collection of patients' samples. This study was supported in part by grants from the National Institutes of Health (Grant CA81247, C49639 and CA100271 to JJM).

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  1. Department of Stem Cell Transplantation and Cell Therapy, Section of Transplantation Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    A Sergeeva, Y Ono, R Rios & J J Molldrem

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Correspondence to J J Molldrem.

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Sergeeva, A., Ono, Y., Rios, R. et al. High titer autoantibodies to GM-CSF in patients with AML, CML and MDS are associated with active disease. Leukemia 22, 783–790 (2008). https://doi.org/10.1038/sj.leu.2405104

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