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

Abstract

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 µg/ml compared to 0·47 µg/ml in patients who did not develop a severe infection (P = 0·01). Conversely, MASP-2 was higher in these patients: median 0·53 µg/ml compared to 0·37 µg/ml, respectively (P = 0·008). When considering M-ficolin levels below 0·36 µg/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.

Fig. 1

Time to severe infection stratified by M-ficolin levels. The 105 patients were divided into two groups according to the levels before chemotherapy as described in the result section: solid line: patients with M-ficolin below 360 ng/ml serum and dashed line: patients with more than 360 ng/ml.

Fig. 2

Time to severe infection stratified by mannan-binding lectin (MBL)-associated serine protease 2 (MASP-2) levels. The 105 patients were divided into two groups according to the levels before chemotherapy, as described in the Results section: solid line: patients with MASP-2 below 430 ng/ml serum and dashed line: patients with more than 430 ng/ml.