Abnormal neutrophil chemotaxis in bone marrow transplant patients correlates with impaired 31D8 monoclonal antibody binding

Abstract

BACKGROUND. 31D8 monoclonal antibody (mAb) has been shown to bind heterogeneously to human neutrophils, identifying subsets of cells which differ in their functional response to chemotactic stimuli. In this study we used 31D8 mAb to determine whether differences in neutrophil subpopulations might explain the long-lasting decreased chemotaxis observed in bone marrow transplant recipients. METHODS. Thirty patients with self-sustaining hematopoiesis 1 to 5 years bone marrow transplantation (BMT) (15 allogeneic and 15 autologous) performed for acute lymphocytic leukemia (ALL, 10 patients) or acute myelogenous leukemia in complete remission (8 patients), Hodgkin's lymphoma (2 patients), chronic myeloid leukemia (8 patients) and severe aplastic anemia (2 patients) were included in the study. Neutrophil chemotaxis was evaluated using a modified Boyden chamber assay and 31D8 binding was determined by indirect immunofluorescence and cytofluorimetric analysis. RESULTS. Neutrophil chemotaxis was significantly impaired in the BMT group with respect to controls. The chemotactic defect strikingly correlated with autologous BMT and, in particular, with ALL as the pre-existing disease. No differences between patients and controls were observed in the percentage of 31D8 bright and dull neutrophils. However, when mean fluorescence intensity (MFI) was analyzed as a relative measure of 31D8 antigen expression on the overall neutrophil population, a significant decrease was observed in neutrophils from BMT patients with respect to controls. As for chemotaxis, the impairment of 31D8 binding was more evident in autologous BMT and strikingly correlated with ALL as the pre-existing disease regardless of age, sex and time since BMT. Moreover, a significant positive correlation between impaired chemotaxis and decreased 31D8 binding was found in our patients. CONCLUSIONS. These findings suggest that the decreased neutrophil chemotaxis observed in some BMT patients may be due in part to circulating 31D8 dull neutrophils, although the causes for the decreased 31D8 binding and for the quite pronounced neutrophil defect in ALL patients remain unknown.