Deficiency of Mannose-Binding Lectin Is a Risk Factor for Invasive Pulmonary Aspergillosis in Patients with Multiple Myeloma: An Analysis of 482 Patients

Abstract

Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in neutropenic cancer patients. Mannose-binding lectin (MBL) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs, leading to complement activation, opsonization, phagocytosis, and cell lysis and is considered an important component of innate immunity. Deficiency of MBL is common due to genetic polymorphisms and has been identified as a risk factor for severe infections among myeloma patients undergoing autologous stem cell transplantation (ASCT). MBL deficiency has also been reported as a predisposing factor for chronic necrotizing pulmonary aspergillosis, a locally invasive infection typically seen in patients with chronic lung disease. The association between MBL deficiency in cancer patients and susceptibility to IPA has never been evaluated.This study investigated whether MBL deficiency, as measured by serum MBL levels, is associated with the development of IPA in patients with multiple myeloma undergoing multiple cycles of antineoplastic chemotherapy including tandem ASCT and post-transplant consolidation chemotherapy. Baseline serum MBL level was measured using ELISA. The frequency of IPA was assessed retrospectively in 482 adult myeloma patients (2007–2008), 50 of whom developed IPA.Association between MBL levels and IPA was analyzed using logistic regression analysis (table 1). Patients with normal serum MBL levels (≥ 1000 ng/mL) had significantly fewer episodes of IPA [(21 in 303 patients; 6.9%); Odds ratio, 0.385; 95% CI (0.212–0.699); P = 0.0017] than patients with low (100–999 ng/mL; 18 episodes in 125 patients (14.4%)) and very low (<100 ng/mL) MBL levels (11 episodes in 54 patients; 20.4%) (Table 1). We conclude that MBL deficiency is associated with more frequent episodes of IPA among patients with myeloma undergoing intensive antineoplastic therapy including ASCT and should be added to the list of risk factors for chemotherapy-related IPA. Baseline MBL level may serve as a predictor for the risk of IPA among such patients. This novel finding may have important therapeutic implications because recombinant Human MBL replacement therapy is now available and could therefore be applied prophylactically to decrease the risk of IPA in MBL-deficient patients receiving chemotherapy.Table 1. Association between serum MBL level and risk of invasive pulmonary aspergillosis (482 pts)AspergillosisMBL (ng/mL)No (n=432)Yes (n=50)RateOdds ratio (95%C.I.)P-value<10043 (10%)11 (22%)11/54 (20% )ReferenceReference100–1000107 (25%)18 (36%)18/125 (14%)0.658 (0.287–1.507)0.32181000282 (65%)21 (42%)21/303 (7%)0.291 (0.131–0.646)0.0024MBL <1000150 (35%)29 (58%)29/179 (16%)Reference