M-ficolin levels are associated with the occurrence of severe infections in patients with haematological cancer undergoing chemotherapy

The pattern recognition molecules H-ficolin, L-ficolin and M-ficolin bind to micro-organisms. They activate the lectin pathway of complement through mannan-binding lectin (MBL)-associated serine proteases (MASPs). Association between low MBL levels and infections in patients undergoing chemotherapy for haematological diseases has been observed previously. We now examine for MASP-2, MASP-3 and ficolin levels. We assessed the concentration of lectin pathway molecules as risk factors for infection in patients with haematological malignancy undergoing chemotherapy. Samples taken before the initiation of chemotherapy covering 117 chemotherapy cycles in 105 patients were available. MASPs and ficolins were measured by time-resolved immunoflourometric assays and the levels related to parameters of infections. End-points included febrile neutropenia, documented infections, bacteraemia or severe infections. Lower M-ficolin concentrations were found in patients who developed a severe infection: median 0.27 mu g/ml compared to 0.47 mu g/ml in patients who did not develop a severe infection (P = 0.01). Conversely, MASP-2 was higher in these patients: median 0.53 mu g/ml compared to 0.37 mu g/ml, respectively (P = 0.008). When considering M-ficolin levels below 0.36 mu g/ml as deficient, the time to development of severe infection was shorter in the M-ficolin deficient group: the hazard ratio was 2.60 (95% confidence interval: 1.23-5.49). No associations were revealed between infections and H-ficolin, L-ficolin or MASP-3. Patients with low M-ficolin are more likely to develop severe infections, whereas MASP-2 showed the opposite.