ABNORMAL NEUTROPHIL CHEMOTAXIS IN BONE-MARROW TRANSPLANT PATIENTS CORRELATES WITH IMPAIRED 31D8 MONOCLONAL-ANTIBODY BINDING

Background. 31D8 monoclonal antibody (mAb) has been shown to bind hete rogeneously to human neutrophils, identifying subsets of cells which d iffer in their functional response to chemotactic stimuli. In this stu dy we used 31D8 mAb to determine whether differences in neutrophil sub populations might explain the long-lasting decreased chemotaxis observ ed in bone marrow transplant recipients.Methods. Thirty patients with self-sustaining hematopoiesis 1 to 5 years after bone marrow transplan tation (BMT) (15 allogeneic and 15 autologous) performed for acute lym phocytic leukemia (ALL, 10 patients) or acute myelogenous leukemia in complete remission (8 patients), Hodgkin's lymphoma (2 patients), chro nic myeloid leukemia (8 patients) and severe aplastic anemia (2 patien ts) were included in the study. Neutrophil chemotaxis was evaluated us ing a modified Boyden chamber assay and 31D8 binding was determined by indirect immunofluorescence and cytofluorimetric analysis. Results. N eutrophil 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 disea se. No differences between patients and controls were observed in the percentage of 31D8 bright and dull neutrophils. However, when mean flu orescence intensity (MFI) was analyzed as a relative measure of 31D8 a ntigen 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 pr e-existing disease regardless of age, sex and time since BMT. Moreover , a significant positive correlation between impaired chemotaxis and d ecreased 31D8 binding was found in our patients. Conclusions. These fi ndings suggest that the decreased neutrophil chemotaxis observed in so me BMT patients may be due in part to circulating 31D8 dull neutrophil s, although the causes for the decreased 31D8 binding and for the quit e pronounced neutrophil defect in ALL patients remain unknown.