L-ficolin Concentrations Research Articles

Assessment of Serum L-Ficolin Level as Inflammatory Marker and Its Correlation with Serum C-Reactive Protein, D-Dimer and Ferritin in a Sample of Iraqi COVID-19 Patients

Subject: At the end of December 2019, a COVID-19 outbreak was reported for the first time in Wuhan, China. Which quickly expanded throughout China, then to 209 nations across America, Europe, Australia, and Asia. More than 50,000 people have died and over one million individuals have been afflicted worldwide, with the number fast rising. COVID-19 has been combated in various ways around the world. The gold standard for COVID-19 diagnosis is real-time fluorescence quantitative reverse transcriptase polymerase chain reaction (reverse transcriptase-polymerase chain reaction, RT-PCR) and viral gene sequencing. Currently, nasopharyngeal swabs from the upper respiratory tract are the most commonly employed nucleic acid detection samples. Objective of the Study: To estimate the level of ficolin in covid-19 patient in moderate and severe disease stage determination (series measurement and follow up) and find the diagnostic tool to early detect the virus to minimize the severity of the disease and further complication. Correlation of serum L-ficolin concentrations with Serum C-Reactive Protein, D-Dimer and Ferritin also to find Prognostic value of L-ficolin will be studied by corelating the treatment outcomes over one month with the three initial L-ficolin level. Materials and Methods: Sixty-two patients will be involved in the study from both sex male and female and different age group (18-80 yr.), the basal level of ficolin will be measure at time of admission of patient (time zero), then further serial measurement will be done on day 7 of admission for precise ficolin monitoring. Results: This study shows elevation of serum L-Ficolin level in survival and non-survival group. Conclusion: The results showed significant negative correlation between L-ficolin levels with the duration of illness (r = -0.377, p =0.020), however there were no significant correlation between L-ficolin levels with other patient‟s parameters.

Evaluation of Endothelial Damage in Sinusoidal Obstructive Syndrome

Introduction: Sinusoidal Obstructive Syndrome (SOS) is a complication derived from the endothelial damage associated to hematopoietic stem-cell transplant (HSCT) conditioning. Although its appearance is highly dependent on patient risk factors, it has an estimated prevalence of 14% and is associated with a high morbidity and with mortality rates than can ascend to 90% at day +100 of transplant in severe cases. New methods to early diagnose SOS are needed in order to minimize the incidence and severity of SOS.Here we present preliminary results of our single center prospective study that aims to measure and validate a panel of biomarkers in plasma [L-Ficolin, hyaluronic acid (HA), vascular adhesion molecule-1 (VCAM1) and plasminogen activator inhibitor-1 (PAI-1)] which have been recently described to be prognostic of the development of SOS (Akil et al, Biol. Blood Marrow Transplant. 21, 1739-1745, 2015).Methods: Twenty-one adult patients undergoing HSCT were recruited (median age 43.5 years old, 20-68), 15 men and 6 women. Three patients (14%) were diagnosed of SOS and received defibrotide (Gentium/Jazz Pharmaceutical) treatment. Diagnosis of SOS was performed based on the Seattle and Baltimore modified Criteria.Citrated blood samples from all patients were obtained before starting conditioning regimen (V0), and at infusion day (V1), 7 (V2) and 14 (V3) after infusion. Three additional samples (V4, V5 and V6) were drawn from those patients with SOS (just before defibrotide and 7 and 14 days after treatment with defibrotide). Samples were centrifuged twice at 23°C (15 min at 1,500 g, and 2 min at 13,000 g) and aliquots were stored at -80ºC until analysis.Phosphatidylserine-MP (Ph-MP) and tissue factor-MP (TF-MP) dependent procoagulant activities were determined with the ZYMUPHEN kits. VCAM1, PAI-1, L-Ficolin and HA concentrations were measured by ELISA.Data from the routine laboratory analysis were also registered.Statistical analyses was performed with SPSS software. Values of p≤0.05 were considered statistically significant.Results : Considering transplant type, 9 were autologous and 9 allogenic in controls, and 3 allogenic in SOS; donor type were 3 unrelated, 6 related and 3 haploidentical in controls, and 3 related and 2 haploidentical in SOS. Conditioning regimen intensity was 7 full, 2 reduced, 8 with busulfan and 1 with total body irradiation in controls and 3 reduced and 2 with busulfan in SOS group. Controls received 2(1-4) previous chemotherapy lines whereas SOS group received 3(2-9).Regarding diseases, 4 presented acute myeloblastic leukemia, 2 acute lymphoblastic leukemia, 3 multiple myeloma, 3 non-Hodgkin's lymphoma and 6 Hodgkin's disease in control group whereas in SOS group 1 had acute myeloblastic leukemia, 1 myelodysplastic syndrome and 1 non-Hodgkin's lymphoma.As observed, occurrence of SOS did not seem to be related to either the malignant disease or number of chemotherapy drugs employed for its treatment or donor type and conditioning regimen.L-Ficolin, a complement activator involved in homeostatic clearance of mitochondria in the liver, seemed to diminished in the SOS group at V3 (wo SOS : 1025±923 ng/mL ; SOS : 680±817 ng/mL). Nevertheless, this diminution was not significant probably due to the few patients with SOS.No differences were observed between patients without and with SOS in plasma levels of markers of endothelial damage VCAM1, PAI-1 and HA, this last a direct indicator of hepatic sinusoidal endothelial cell function.Procoagulant activity associated to Ph-MP was lower in patients with SOS (p=0.023) whereas that associated to TF-MP was unaffected.Plasma levels of VCAM1 and HA increased along time in both groups. After treatment with defibrotide these values achieved steady levels in SOS patients (V4 and V5). On the other hand, PAI-1 did not change over time.SOS patients presented at V3 higher total bilirrubin (wo SOS: 0.86±0.53 mg/dL; SOS: 2.31±0.18 mg/dL, p=0.008) and lower albumin levels (wo SOS: 3.5±0.3 g/dL; SOS: 2.7±0.1 g/dL)Conclusions: Our results indicate that endothelial damage is present in all patients undergoing HSCT and that treatment of SOS patients with defibrotide might restrain this injury. Due to the low number of patients included so far, we cannot conclude anything about the value of biomarkers proposed to serve as predictors of SOS onset. Our study is still open and recruiting patients.This work was supported by Jazz Pharmaceutical DisclosuresNo relevant conflicts of interest to declare.

L-Ficolin and Capsular Polysaccharide-Specific IgG in Cord Serum Contribute Synergistically to Opsonophagocytic Killing of Serotype III and V Group B Streptococci

Group B streptococci (GBS; Streptococcus agalactiae) are the most common cause of neonatal sepsis and meningitis. Serotype-specific IgG antibody is known to protect neonates against GBS infections by promoting opsonophagocytosis. The L-ficolin-mediated lectin pathway of the complement is also a potential mechanism for opsonization of GBS, because L-ficolin activates the complement after binding to serotype Ib, III, V, VI, and VIII GBS. In the present study, we investigated how L-ficolin and serotype-specific IgG in cord sera contribute to opsonophagocytic killing of GBS. Neither L-ficolin nor serotype-specific IgG concentrations correlated with C3b deposition on serotype Ib and VI GBS, suggesting L-ficolin- and serotype-specific IgG-independent mechanisms of complement activation. The percentage of serotype VIII GBS killed was high regardless of the concentration of L-ficolin and IgG. In contrast, L-ficolin and serotype-specific IgG can each initiate C3b deposition on serotype III and V GBS and promote phagocytosis by polymorphonuclear leukocytes, but L-ficolin and serotype-specific IgG together promote opsonophagocytic killing to a greater extent than does either alone in vitro. This synergy was observed when serotype III-specific IgG concentrations were between 1 and 6 μg/ml and when serotype V-specific IgG concentrations were between 2 and 5 μg/ml. Concentrations of serotype III-specific IgG in cord blood above 7 μg/ml are considered protective for neonates colonized with GBS, but most neonates with IgG levels of less than 7 μg/ml do not develop GBS infections. The data presented here suggest that L-ficolin enhances opsonophagocytosis of serotype III and V GBS when serotype-specific IgG alone is suboptimal for protection.

Increased titers of anti-Saccharomyces cerevisiae antibodies in Crohn's disease patients with reduced H-ficolin levels but normal MASP-2 activity

Background and aimsMannan-binding lectin (MBL) and ficolins are microbial pattern recognition molecules that activate the lectin pathway of complement. We previously reported the association of MBL deficiency with anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn's disease (CD). However, ASCA are also frequently found in MBL-proficient CD patients. Here we addressed expression/function of ficolins and MBL-associated serine protease-2 (MASP-2) regarding potential association with ASCA. MethodsASCA titers and MBL, ficolin and MASP-2 concentrations were determined by ELISA in the serum of patients with CD, ulcerative colitis (UC), and in healthy controls. MASP-2 activity was determined by measuring complement C4b-fixation. Anti-MBL autoantibodies were detected by ELISA. ResultsIn CD and UC patients, L-ficolin concentrations were significantly higher compared to healthy controls (p<0.001 and p=0.029). In contrast, H-ficolin concentrations were slightly reduced in CD and UC compared to healthy controls (p=0.037 for UC vs. hc). CD patients with high ASCA titers had significantly lower H-ficolin concentrations compared to ASCA-low/negative CD patients (p=0.009). However, MASP-2 activity was not different in ASCA-negative and ASCA-positive CD patients upon both, ficolin- or MBL-mediated MASP-2 activation. Finally, anti-MBL autoantibodies were not over-represented in MBL-proficient ASCA-positive CD patients. ConclusionsOur results suggest that low expression of H-ficolin may promote elevated ASCA titers in the ASCA-positive subgroup of CD patients. However, unlike MBL deficiency, we found no evidence for low expression of serum ficolins or reduced MASP-2 activity that may predispose to ASCA development.

Factors of the Lectin Pathway of Complement Activation and Their Clinical Associations in Neonates

This paper summarizes the data concerning soluble defense lectins (mannan-binding lectin, M-ficolin, L-ficolin, and H-ficolin) with the unique ability to activate complement and their associated serine proteases (MASPs) in neonates. The clinical importance of deficiencies of these immune factors is presented in aspects of perinatal mortality, premature births, and low birthweight. Prenatal serum concentrations of L-ficolin, H-ficolin, and MASP-2 (and probably M-ficolin) correlate with gestational age and birthweight. The relationship of serum MBL to gestational age is controversial. The MBL2 genotypes XA/O and O/O (associated with low-serum MBL) are associated with perinatal infections, whereas the high serum MBL-conferring A/A genotypes may be associated with prematurity. Low-serum L-ficolin concentrations, but not low-serum H-ficolin concentrations, are also associated with perinatal infections. Much of the literature is inconsistent, and the relationships reported so far require independent confirmation at both gene and protein levels. Our preliminary conclusion is that these soluble defense lectins play a protective role in the neonate, and that insufficiency of such factors contributes to the adverse consequences of prematurity and low birthweight.

The potential role of the lectin pathway of complement in the host defence of full-term intrauterine growth restricted neonates at birth

Objective: To prospectively investigate the potential role of the lectin pathway of complement in intrauterine-growth-restriction (IUGR, associated with impaired immunocompetence and increased risk for neonatal infections), by determining cord blood concentrations of mannose-binding lectin (MBL), H-ficolin and L-ficolin (important mediators of neonatal innate immunity) in IUGR and appropriate for gestational age (AGA) pregnancies. Furthermore, we aimed to describe correlations among cord blood MBL, H- and L-ficolin concentrations and with several demographic parameters of the infants at birth. Methods: Serum MBL, H- and L-ficolin concentrations were determined by ELISA in 154 mixed arteriovenous cord blood samples from IUGR (n = 50) and AGA (n = 104) singleton full-term infants. Results: Cord blood MBL concentrations were significantly lower in IUGR cases than AGA controls (p = 0.029). No differences in cord blood H- and L-ficolin concentrations were observed between groups. In the IUGR group, cord blood MBL concentrations negatively correlated with respective L-ficolin ones (r = −0.442, p = 0.001). Conclusions: The relatively decreased MBL expression in IUGR fetuses at term could possibly contribute to IUGR-associated neonatal immunodeficiency, predisposing to increased susceptibility to infections. The negative correlation between MBL and L-ficolin concentrations in the IUGR group might suggest an underlying immune variation and needs to be further investigated.

Cord Blood H- and L-Ficolin Concentrations in Term Pregnancies with Normal and Restricted Fetal Growth

Background and Aims: Ficolins H and L are serum defence proteins, mainly expressed in the liver and differing in ligand specificity. They initiate the lectin pathway of complement activation through association with mannose-binding-protein- associated proteases (MASPs). Ficolins are implicated in the pathogenesis of infectious and autoimmune diseases, apoptosis and preeclampsia. H-ficolin is a powerful direct opsonin binding to late apoptotic cells. This study aimed to determine H- and L-ficolin cord blood concentrations in appropriate-for-gestational-age (AGA) and intrauterine-growth-restricted pregnancies (IUGR), associated with excessive apoptosis, uteroplacental vascular insufficiency and activation of the innate immune system. Furthermore to investigate possible correlations of H- and L-ficolin concentrations with several demographic parameters of infants at birth. Methods: Serum H- and L-ficolin concentrations were determined by ELISA in 160 mixed arteriovenous cord blood samples from 50 IUGR and 110 AGA singleton full-term pregnancies. Results: No significant differences in cord blood H- and L-ficolin concentrations were observed between IUGR and AGA groups. The effect of customized centile, birthweight, gender, gestational age, parity and maternal age on cord blood H- and L-ficolin concentrations was not significant in both groups. Conclusions: Lack of differences in cord blood H- and L- ficolin concentrations at term between IUGR and AGA groups possibly suggests that they are not directly implicated in the pathophysiological processes of IUGR. Possibly this happens because the lectin pathway of complement activation, as far as ficolins are concerned, may not be fully functional at birth.

L-ficolin (ficolin-2) insufficiency is associated with combined allergic and infectious respiratory disease in children

We previously reported an association between relative L-ficolin deficiency and recurrent respiratory infections co-existing with allergic disorders in children. To confirm and extend this preliminary finding, we performed a prospective study on children of a similar age (mean 8.9 years) designed to establish whether the principal relationship was with infection or allergy. Serum L-ficolin values in healthy children were normally distributed with a mean value of 3838ng/ml. L-ficolin concentrations were generally lower in patients with asthma and/or allergic rhinitis with (mean 3413ng/ml; p=0.02) or without (3512ng/ml; p<0.07) respiratory infections, but not in patients with respiratory infections without allergic disease (3623ng/ml; p=0.2). The lower average values in the group comprised of children with respiratory allergy and infections were largely due to a high proportion of very low values: 18.3% had values below 2150ng/ml compared to only 5.5% of healthy controls (OR=3.9; p=0.01). This relationship was not apparent in the groups characterized by allergy without infection or infections without allergy. An association between mannan-binding lectin (MBL) insufficiency and recurrent respiratory infections was also confirmed. One of the patients was MASP-2 deficient, evidenced both by MASP2 genotyping and by lectin pathway activity measurement. In conclusion, L-ficolin may confer some protection from microorganisms that exacerbate allergic inflammation in the lung and its relative deficiency may contribute to enhanced susceptibility to respiratory infections. MBL insufficiency and MASP-2 deficiency are risk factors for recurrence of infections independently of allergic disease.

Stable bronchiectasis is associated with low serum L‐ficolin concentrations

Bronchiectasis is a common chronic respiratory condition with recurrent cough and sputum production and recurrent chest infections. It is characterised by pathological dilatation of the bronchi thought to result from infection and inflammation. It was hypothesised that impaired innate immunity might influence susceptibility to this disease process. The aim of the present study was to look for an association between bronchiectasis and insufficiency of either mannan-binding lectin (MBL) or L-ficolin. MBL and L-ficolin were measured by Enzyme-linked Immunosorbent Assay (ELISA) in sera from 119 clinically stable bronchiectasis patients, and compared with 43 age-matched disease controls admitted to hospital with community-acquired pneumonia, as well as healthy blood donors (168 for L-ficolin and 564 for MBL). Average (mean and median) serum L-ficolin concentrations were lower in the bronchiectasis patients (P < 0.04), but average MBL values did not differ significantly between the three groups. Relative L-ficolin deficiency was more frequent in bronchiectasis patients compared with blood donors (P <or= 0.002), whereas MBL insufficiency was associated with pneumonia. A relative lack of serum L-ficolin might predispose to the development of bronchiectasis, although other explanations for the observed association are possible.

Two factors of the lectin pathway of complement, l-ficolin and mannan-binding lectin, and their associations with prematurity, low birthweight and infections in a large cohort of Polish neonates

Ficolins and one collectin, mannan-binding lectin (MBL), are the only factors known to activate the lectin pathway (LP) of complement. There is considerable circumstantial evidence that MBL insufficiency can increase susceptibility to various infections and influence the course of several non-infectious diseases complicated by infections. Much less information is available concerning l-ficolin. We report the results of a prospective study to investigate any association between either MBL deficiency or l-ficolin deficiency with prematurity, low birthweight or perinatal infections in a large cohort of Polish neonates, representing an ethnically homogenous population (n=1832). Cord blood samples were analysed to determine mbl-2 gene variants, MBL concentrations and MBL-MASP-2 complex activities (MBL-dependent lectin pathway activity) as well as l-ficolin levels. Median concentrations of l-ficolin and MBL were 2500 and 1124ng/ml, respectively, while median LP activity was 272mU/ml. After genotyping, 60.6% of babies were mbl-2 A/A, 35.4% were A/O and 4% were O/O genotypes. We found relative l-ficolin deficiency to be associated with prematurity, low birthweight and infections. l-Ficolin concentration correlated with gestational age and with birthweight, independently of gestational age. Preterm deliveries (<38 weeks) occurred more frequently among neonates with low LP activity but not with those having low serum MBL levels. Similarly, no association of serum MBL deficiency with low birthweight was found, but there was a correlation between LP activity and birthweight. Genotypes conferring very low serum MBL concentrations were associated with perinatal infections, and high-MBL-conferring genotypes were associated with prematurity. Our findings suggest that l-ficolin participates in host defence during the perinatal period and constitute the first evidence that relative l-ficolin deficiency may contribute to the adverse consequences of prematurity. Some similar trends were found with facets of MBL deficiency, but the observed relationships were weaker and less consistent.

Extremes of l-ficolin concentration in children with recurrent infections are associated with single nucleotide polymorphisms in the FCN2 gene

L-ficolin (also called ficolin-2, P35 or hucolin) is a soluble pattern recognition molecule of suspected importance in anti-microbial immunity. It activates the lectin pathway of complement and acts as an opsonin. l-ficolin, encoded by the FCN2 gene, recognizes microbial polysaccharides and glycoconjugates rich in GlcNAc or GalNAc. We report here data concerning four single nucleotide polymorphisms (SNPs) of the FCN2 gene and their relationship to l-ficolin serum concentrations. There are two pairs of SNPs in linkage disequilibrium: ss32469536 (located in promoter) with rs7851696 (in exon 8) and ss32469537 (promoter) with ss32469544 (exon 8). We selected groups possessing low or high serum l-ficolin concentrations (<or= 2.8 microg/ml or >or= 4.5 microg/ml, respectively) from Polish children suffering from recurrent respiratory infections (n = 146). Low l-ficolin levels were associated with variant alleles for ss32469536 and rs7851696 and normal alleles for ss32469537 and ss32469544. Conversely, high l-ficolin levels were associated with variant alleles of ss32469537 and ss32469544. FCN2 genotyping should be a valuable additional tool for disease association studies.

Functional polymorphisms in the FCN2 gene are not associated with invasive pneumococcal disease

L-ficolin is a pattern-recognition molecule which binds lipoteichoic acid and Gram-positive bacteria and activates the lectin pathway of complement. Five common functional polymorphisms have recently been identified in the FCN2 gene which encodes L-ficolin: three promoter polymorphisms (at positions −986, −602 and −4) which affect serum L-ficolin concentration, and two non-synonymous polymorphisms (Thr236Met and Ala258Ser) which influence carbohydrate binding. We studied the frequencies of these polymorphisms in individuals with invasive pneumococcal disease (IPD) and a control group. Although the five FCN2 polymorphisms were each present in the UK Caucasian population studied, no significant associations were observed between the FCN2 polymorphisms and susceptibility to IPD. This is in contrast to mannose-binding lectin deficiency, which we have previously shown to be associated with increased susceptibility to IPD. Although we are unable to exclude small effects of FCN2 genetic variation on susceptibility to IPD, the result suggests that L-ficolin may not be critical for host defence against pneumococcal infection.

Association between mannan-binding lectin and impaired lung function in cystic fibrosis may be age-dependent

An association between mannan-binding lectin (MBL) status and severity of lung function impairment in cystic fibrosis (CF) has been found in several studies, but not in others. To explore the possible basis for discrepancies in the literature, we related both MBL and L-ficolin concentrations to lung function and examined the results in relation to the age of the patients. For patients under 15 years of age, those with MBL < 200 ng/ml had better lung function than those with MBL > 200 ng/ml [median forced expiratory volume in 1 s (FEV(1)), 99% versus 83%; P = 0.05]. For patients over 15 years of age, those with MBL < 200 ng/ml had poorer lung function than those with MBL > 200 ng/ml (median FEV(1), 44% versus 55%; P = 0.1). Also, for the over 15-year-olds, the proportion of patients with FEV(1) values below the median was greater in the MBL-insufficient subgroup (P < 0.04). In other words, relative deficiency of MBL appears to accelerate the age-related decline in lung function in CF patients. No corresponding relationships could be found between L-ficolin concentration and lung function. These findings and interpretation lend support to the potential value of MBL replacement therapy in a small minority of cystic fibrosis patients.

L-ficolin in children with recurrent respiratory infections

The lectin pathway of complement activation is used by a collectin, mannan-binding lectin (MBL), and two ficolins, L-ficolin and H-ficolin, to opsonize microorganisms for phagocytosis. We published evidence recently that MBL insufficiency is associated with recurrent respiratory infections in childhood. We have now measured serum L-ficolin in 313 respiratory infection patients and 74 healthy control children. L-ficolin concentrations below the lower limit of the control group were found in 6% of the patients (P <0.02) and were associated most strongly with children having co-existing atopic disorders (11%; P=0.002). We suggest that L-ficolin may have a role in protection from microorganisms complicating allergic disease.

L-ficolin specifically binds to lipoteichoic acid, a cell wall constituent of Gram-positive bacteria, and activates the lectin pathway of complement.

The lectin pathway of complement is activated when a carbohydrate recognition complex and associated serine proteases binds to the surface of a pathogen. Three recognition subcomponents have been shown to form active initiation complexes: mannan-binding lectin (MBL), L-ficolin, and H-ficolin. The importance of MBL in antimicrobial host defense is well recognized, but the role of the ficolins remains largely undefined. This report shows that L-ficolin specifically binds to lipoteichoic acid (LTA), a cell wall component found in all Gram-positive bacteria. Immobilized LTA from Staphylococcus aureus binds L-ficolin complexes from sera, and these complexes initiate lectin pathway-dependent C4 turnover. C4 activation correlates with serum L-ficolin concentration, but not with serum MBL levels. L-ficolin binding and corresponding levels of C4 turnover were observed on LTA purified from other clinically important bacteria, including Streptococcus pyogenes and Streptococcus agalactiae. None of the LTA preparations bound MBL, H-ficolin, or the classical pathway recognition molecule, C1q.

No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections.

Chemotherapy causes neutropenia and an increased susceptibility to infection. Recent reports indicate that mannan-binding lectin (MBL) insufficiency is associated with an increased duration of febrile neutropenia and incidence of serious infections following chemotherapy for haematological malignancies. We aimed to confirm or refute this finding and to extend the investigation to the plasma ficolins, P35 (L-ficolin) and the Hakata antigen (H-ficolin). MBL, L-ficolin and H-ficolin were measured in 128 patients with haematological malignancies treated by chemotherapy alone or combined with bone marrow transplantation. Protein concentrations were related to clinical data retrieved from medical records. MBL concentrations were elevated compared with healthy controls in patients who received chemotherapy, while L-ficolin concentrations were decreased and H-ficolin levels were unchanged. There was no correlation between MBL, L-ficolin or H-ficolin concentration and febrile neutropenia expressed as the proportion of neutropenic periods in which patients experienced fever, and there was no relation between abnormally low (deficiency) levels of MBL, L-ficolin or H-ficolin and febrile neutropenia so expressed. Patients with MBL < or =0.1 microg/ml had significantly more major infections than no infections within the follow-up period (P<0.05), but overall most patients had signs or symptoms of minor infections irrespective of MBL concentration. Neither L-ficolin nor H-ficolin deficiencies were associated with infections individually, in combination or in combination with MBL deficiency. MBL, L-ficolin and H-ficolin, independently or in combination, did not have a major influence on susceptibility to infection in these patients rendered neutropenic by chemotherapy. These results cast doubt on the potential value of MBL replacement therapy in this clinical context.