Naturally occurring and therapy-induced antibodies to human granulocyte colony-stimulating factor (G-CSF) in human serum

Abstract

Sera were obtained from two groups of patients. Group A included 7 patients with low-grade non-Hodgkin's lymphoma treated with three or more cycles of standard-dose chemotherapy and recombinant human granulocyte-colony stimulating factor (rhG-CSF). The cytokine was administered to half the patients after the first chemotherapy cycle and to the other half after the second according to a randomized design and then to all patients from the third chemotherapy cycle on, until documented hemopoietic reconstitution. Group B included 3 patients with high-grade non-Hodgkin's lymphoma, 1 patient with resistant Hodgkin's disease, and 1 patient with multiple myeloma who received high-dose chemotherapy and rhG-CSF. Anti-G-CSF antibodies were detected in the sera of 4 patients. Both immunoglobulin IgM and IgG antibodies were detected at low levels in pretreatment sera from one group A patient. IgG antibody titers increased markedly during the first and second periods of G-CSF administration. IgG class antibodies developed in 3 groups B patients during the first course of rhG-CSF administration. Circulating anti-G-CSF antibodies did not seem to affect hematological recovery. Low levels of anti-G-CSF antibodies were also detected in sera (15/135) from different healthy adults and in sera (5/40) from umbilical cord blood. Saturable antibody binding and competition enzyme-linked immunosorbent assay (ELISA) and immunoblotting confirmed antibody specificity.

The role of antibodies in enzyme treatments and therapeutic strategies

“…Depending upon the extent of the immune response, inhibitors neutralise the effect of infused protein, leading to a reduction in activity to less than 1%. A similar phenomenon is reported with other therapeutic proteins such as recombinant human insulin, porcine insulin [5e7] growth hormone [8], granulocyte colony stimulating factor [9], erythropoietin [10] and interferon [11].…”

Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor

“…21 Development of antibodies to G-CSF did not alter resting blood counts or G-CSF response. 22 The mechanism for the immune response to PEG-rHuMGDF and TPO is unknown. Although protein conjugation with polyethylene glycol was previously found to reduce antibody responses compared with results with the unmodified molecule, 23 the prolonged, repeated exposure of skin dendritic cells to PEGrHuMGDF likely assisted in the development of an immune response.…”

Thrombocytopenia caused by the development of antibodies to thrombopoietin

“…27 Low levels of antibody to G-CSF have been found in 11% of healthy adults and in 13% of cord blood samples but with no effect on the neutrophil count. 28 These autoantibodies rose after administration of G-CSF but lacked clinical significance. This is in contrast to the aforementioned antibodies formed after the administration of molgramostim that reduced the half-life and biological effect of the recombinant drug but did not affect baseline WBC production.…”