Anti-GM-CSF autoantibodies in myeloid leukemias

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional cytokine integral to the differentiation, proliferation, and activation of various immune cells, especially those of myeloid lineage. Recombinant human GM-CSF (rhGM-CSF) plays a critical role after high-dose chemotherapy, hematopoietic cell transplantation, and high-dose irradiation by accelerating myeloid recovery and reducing the risk of severe infections. As an adjuvant in anti-tumor vaccines, rhGM-CSF stimulates the differentiation and activation of dendritic cells and promotes their recruitment to tumor sites. Despite the therapeutic benefits, rhGM-CSF can induce the production of anti-GM-CSF-autoantibodies (GM-CSF-Ab) that have been implicated in rare diseases, such as autoimmune pulmonary alveolar proteinosis. These antibodies can neutralize GM-CSF activity, impairing macrophages and neutrophils. Furthermore, anti-GM-CSF-Ab have been linked to myeloid leukemias, where they are associated with active disease. The mechanisms behind anti-GM-CSF-Ab production and their role in disease progression remain poorly understood. This review article provides an overview of GM-CSF and anti-GM-CSF-Ab.