Role Of Mannan-binding Lectin Research Articles

Mannan-binding lectin at supraphysiological concentrations inhibits differentiation of dendritic cells from human CD14+ monocytes.

Mannan-binding lectin (MBL), a circulating C-type lectin, is an important member of the defense collagen family. It exhibits a high potential for recognizing broad categories of pathogen-associated molecular patterns and initiating complement cascade responses. DCs are well-known specialist antigen-presenting cells that significantly trigger specific T cell-mediated immune responses. In our previous study, it was observed that high concentrations of MBL significantly attenuate LPS-induced maturation of monocyte-derived DCs (MoDCs). In the current study, it was postulated that MBL at similar supraphysiological concentrations would affect early differentiation of MoDCs in some way. CD14(+) monocytes from human peripheral blood mononuclear cells were cultured with granulocyte-macrophage colony-stimulating factor and IL-4 in the presence or absence of physiological (1 µg/mL) and supraphysiological concentrations (20 µg/mL) of MBL protein, respectively. Phenotypic analysis indicated that the differentiated DCs incubated with high concentrations of MBL expressed MHC class II and costimulatory molecules (e.g., CD80 and CD40) more weakly than did control groups. The secretion of IL-10 and IL-6 increased markedly, whereas their mixed lymphocyte reaction-stimulating capacity decreased. Members of the signal transducer and activator of transcription family were also found to be differentially regulated. Thus, beyond the role of MBL as an opsonin, our data reveal a possible inhibitory effect of MBL at high concentrations in monocyte-DC transition, which probably provides one way of regulating adaptive immune responses by strict regulation of DCs, making MBL a better prospect for controlling relevant pathological events such as autoimmune diseases.

Protection Against Renal Ischemia Reperfusion Injury By Dietary Restriction and Fasting Through Downregulation of Mannan-Binding Lectin.

Introduction Ischemia-reperfusion injury (IRI) remains an important problem in transplantation. We recently showed that Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, plays a pivotal role. Preoperative dietary restriction (DR) offers robust protection against renal IRI in mice. However, the mechanism remains to be elucidated. Therefore, we investigated the impact of DR on MBL and the role of MBL in the protective mechanism of DR. Materials and Methods Male C57Bl/6 mice were fed ad libitum (AL) or underwent 72hrs fasting (FA) or 2 weeks 30%DR (n=8/group). Protein and functional activity of serum MBL-A and -C after DR were assessed as well as liver mRNA analysis. In vivo, IRI was induced by 37 min of bilateral clamping of the renal pedicles in all three groups. After clamping, mice were sutured and part of them was reconstituted via intraperitoneal injection of 100 μg/ml of human MBL. All mice were subsequently observed for a period of 7 days. Results Assessment of mRNA showed a significant downregulation in liver MBL expression in both 30%DR and FA (p≤0.004) groups. In line with this, both MBL-A and MBL-C concentrations were significantly lower (p≤0.001) after 30% DR (A=15.4 μg/ml; C=89.4 μg/ml) and FA (A=12.4 μg/ml; C=49.5 μg/ml) compared to respectively 19.9 μg/ml MBL-A and 109.6 μg/ml MBL-C in the AL group. Furthermore, we observed a significant downregulation of lectin pathway activity in both groups. Importantly, reconstitution of MBL following reperfusion breaks DR-induced protection against renal IRI in the 30%DR group, but not in the FA group. Conclusion Dietary interventions downregulate the expression and presence of MBL. Reconstitution of MBL following reperfusion breaks DR-induced protection and strongly suggests that downregulation via the lectin pathway may be one of the mechanisms by which dietary interventions protect against renal IRI.

Mannan-Binding Lectin in Diabetic Kidney Disease: The Impact of Mouse Genetics in a Type 1 Diabetes Model

Background. Mannan-binding lectin (MBL) is involved in the development of diabetic nephropathy. MBL is a part of the innate immune system where it can activate the complement system. Serum MBL level predicts later renal impairment in diabetes patients. Direct involvement of MBL in the development of diabetic kidney disease is observed in one animal strain. However, this involvement may differ among the animal strains. We thus examined the impact of the genetic background on the role of MBL in diabetic nephropathy. Materials/Methods. C57BL/6JBomTac and 129S6/SvEvTac mice were compared. In both strains, experimental type 1 diabetes was induced in wild-type (WT) and MBL-knockout (MBL-KO) mice by streptozotocin. Nondiabetic WT and MBL-KO mice were used as controls. We tested if MBL modified the diabetes-induced kidney changes by two-way ANOVA allowing for interaction. Results. MBL aggravated diabetes-induced kidney growth and glomerulus enlargement in C57BL/6JBomTac mice. MBL did not modify diabetes effects on glomerular basement membrane thickness or mesangial volume in any strain. Diabetes-induced changes in renal gene transcription of growth factors and matrix components were unaffected by MBL. Conclusions. Strain-specific MBL effects were found on downstream diabetic kidney changes. This emphasizes the importance of genetic background in this model of diabetic complications.

Mannan-binding lectin deficiency in pediatric patients with inflammatory bowel disease

Objective. The incidence of inflammatory bowel disease (IBD) in Europe has increased significantly. At least a fourth of patients are children. Mannan-binding lectin (MBL) is believed to be an important component of innate immunity, acting as an opsonin and activator of the lectin pathway (LP) of complement. The data relating any of the LP factors to IBD are sparse and contradictory and were obtained mainly from adult patients. The aim of this study was to investigate the possible role of MBL in Crohn's disease (CD) and ulcerative colitis (UC) in children. Methods. MBL2 gene single nucleotide polymorphisms (PCR-RFLP) and MBL concentrations (ELISA) were determined. Results. The frequency of MBL2 gene variants responsible for MBL deficiency (LXPA/O and O/O) is significantly higher in CD patients compared with controls or children with UC. A relatively high frequency of the codon 52 mutation (D allele) was noted in these patients. Practically no difference was found between UC and control (C) groups. Similarly, the average MBL levels as well as the number of MBL-deficient (MBL concentrations < 150 ng/ml) individuals differed between CD patients and controls or children suffering from UC. Again, there was no difference between UC and C groups. Conclusions. These data suggest that MBL deficiency may be associated with CD but not with UC in pediatric patients. The possible role of MBL in IBD requires confirmation in larger series and further investigation of the mechanisms involved.

Fibrosis severity and mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex in HCV-infected patients

Background and study aims Mannan-binding lectin (MBL) is a collectin synthesised in the liver and secreted into the bloodstream. It binds micro-organisms via interactions with glycans on the target surface. Bound MBL subsequently activates MBL-associated serine protease proenzymes (MASPs). Several studies have investigated the possible role for MBL in hepatitis C virus (HCV) infection by examining MBL levels and polymorphisms in relation to disease progression and in response to treatment. The aim of this study was to investigate the relation of the activity of MBL and MBL/MASP-1 complex in sera of patients with mild and severe chronic HCV infection and outcome of HCV infection. Patients and methods Serum level of MBL and functional assays for MBL/MASP-1 complex activity were assayed in sera of 80 patients with chronic HCV infection. Patients were divided into two groups according to the results of the liver biopsy, group I (40 HCV patients had mild hepatic fibrosis, Ishak fibrosis stages 0–1) and group II (40 HCV patients had severe hepatic fibrosis, Ishak fibrosis stages 5–6), in addition to 20 control subjects as group III. The analysis of the MBL/MASP-1 complex activity at 0, 3 and 6 months was performed in all patients. Results: Serum levels of MBL and MBL/MASP-1 complex activity were higher in sera of patients with chronic HCV liver disease compared to those in control subjects. There was a correlation between the activity of the MBL/MASP-1 complex and the severity of fibrosis ( P = 0.003). MBL/MASP-1 complex activity was associated more significantly with severe fibrosis in comparison to MBL concentration. Conclusion MBL and MBL/MASP-1 complex activities play a key role in first-line host defence mechanism against certain infectious agents including HCV infection. However, it is also likely that the role of MBL and MBL/MASP-1 complex activity extends beyond this restricted infection-related view in that it appears to be a key regulator of inflammation.

Mannan-binding lectin (MBL) and MBL-associated serine protease-2 in children with cancer

Mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are two key components of the lectin-pathway of complement-activation. Information on the potential role of lectin-pathway components in carcinogenesis versus immune surveillance of cancer is scarce. This study aimed to determine if serum concentrations of MBL and MASP-2 differ between children with cancer and healthy age-matched controls. In this retrospective multicentre study, MBL and MASP-2 were measured by commercially available ELISA in frozen remnants of serum taken at diagnosis in paediatric patients with cancer. For six diagnostic groups, these concentrations were compared with serum concentrations of age-matched healthy controls using exact Wilcoxon signed-rank tests. MBL and MASP-2 were measured in serum of 372 patients. MBL was significantly higher in patients with solid tumours vs. controls (median, 2,799 vs. 1,917 μg/L; P = 0.008), and MASP-2 was significantly higher in patients with acute lymphoblastic leukaemia (406 vs. 317 μg/L; P = 0.009), Non-Hodgkin lymphoma (361 vs. 293 μg/L; P = 0.037) and CNS tumors (463 vs. 296 μg/L; P = 0.002). These results may indicate a role of MBL and MASP-2 in the initiation or progression of specific paediatric cancers, while other mechanisms remain possible as well. Larger, disease-specific studies are warranted for confirmation and for elucidation of the underlying mechanisms.

Mannan-binding lectin deficiency results in unusual antibody production and excessive experimental colitis in response to mannose-expressing mild gut pathogens

BackgroundIn Crohn's disease (CD) the deficiency of mannan-binding lectin (MBL) is associated with an increased prevalence of anti-Saccharomyces cerevisiae antibodies (ASCA) and with complicated phenotypes of the disease. However, the...

Is there a role for mannan-binding lectin in the diagnosis of inflammatory bowel disease?

Mannan-binding lectin (MBL) activates the lectin-complement pathway as part of the innate immune defence by binding to the surface of microorganisms. Therefore, MBL2 presents an interesting candidate gene for the inflammatory bowel diseases, ulcerative colitis (UC) and Crohn's disease (CD). In our study, we evaluated the MBL serum concentrations and genotypes for diagnostic and classification purposes of patients with CD and UC. The MBL serum concentration was analysed in 98 CD patients and in 83 UC patients. In total, 82 patients with inflammatory rheumatic disorders and 189 healthy individuals served as controls. All study subjects were genotyped for the MBL2 polymorphisms G54D, G57E and R52C and the NOD2 (CARD15) mutations R702W, G908R and L1007fsinsC. Neither the median MBL serum concentration nor the MBL2 genotype distribution differed significantly between cohorts. Measurement of MBL serum concentrations offers no benefit for the diagnosis of CD or UC.

Mannan-binding lectin in women with a history of recurrent vulvovaginal candidiasis

Objectives To determine the serum concentration of mannan-binding lectin (MBL), a component of the innate immune system, in women with a history of recurrent vulvovaginal candidiasis (RVVC) and to correlate the result to candida-cultures, contraceptive use, if any, and to different antifungal therapies. Study design Twenty-nine women with a history of RVVC were investigated. Cultures of vulvar and vaginal samples were grown on chromogenic agar. Serum levels of MBL were determined by a sandwich time-resolved immunofluorometric assay, using anti-MBL coated microtiter wells containing samples, which were washed, incubated with biotinylated anti-MBL followed by europium-labeled streptavidin and measured by time-resolved flourometry. Results The median MBL level was higher in the RVVC cases than in 30 women with no history of genital candida infection who served as a comparison group ( p = 0.006). It was also higher in the candida-positive than in the culture-negative RVVC ( p = 0.02). The median concentration of MBL was also higher in hormonal contraceptive users as compared to condom-users and those using no contraceptive at all ( p = 0.03). Conclusion The result indicates a role of MBL in RVVC and the production may correlate to vulvar/vaginal colonization by Candida, hormonal contraceptive use, and antifungal therapies.

The Role of Mannan-Binding Lectin (MBL) Gene Polymorphism in Ulcerative Colitis.

Series studies suggest that enteropathogenic microorganisms play a substantial role in the clinical initiation and relapses of ulcerative colitis (UC). Mannan-binding lectin (MBL) is an important constituent of the innate immune system, and deficiency of MBL has been reported to increase the overall susceptibility of an individual to infectious disease. This study was aimed to investigate the associations between polymorphisms of the MBL gene and UC. Recruited in this study were 108 Japanese patients with UC and 144 healthy control subjects. Polymorphism at codon 54 of exon 1 of the MBL gene was investigated by polymerase chain reaction based restriction fragment length polymorphism. In general, no significant difference in MBL polymorphism was found between UC patients and health controls. However, the frequency of A carriers was significantly higher in the relapsing cases than controls (Odds ration = 2.19, 95%CI, 1.10–4.34; p = 0.023), and similar tendency was also found in A/A genotype. In conclusion, the polymorphism at codon 54 of exon 1 of the MBL gene associated with the susceptibility to the relapsing phenotype of ulcerative colitis. It suggests that codon 54 A variants of MBL gene may have an increased risk for the flare-ups of UC.

Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex

Mannan-binding lectin (MBL) binds microorganisms via interactions with glycans on the target surface. Bound MBL subsequently activates MBL-associated serine protease proenzymes (MASPs). A role for MBL in hepatitis C virus (HCV) infection had been indicated by previous studies examining MBL levels and polymorphisms in relation to disease progression and response to treatment. We undertook this study to investigate a possible relationship between disease progression and functional MBL/MASP-1 complex activity. A functional assay for MBL/MASP-1 complex activity was employed to examine serum samples from patients with chronic HCV infection, non-HCV liver disease and healthy controls. Intrapatient consistency of MBL/MASP-1 complex activity levels was assessed in sequential samples from a subgroup of patients. Median values of MBL/MASP-1 complex activity were higher in sera from patients with liver disease compared with healthy controls. MBL/MASP-1 complex activity levels correlate with severity of fibrosis after adjusting for confounding factors (P = 0.003). MBL/MASP-1 complex activity was associated more significantly with fibrosis than was MBL concentration. The potential role of MBL/MASP-1 complex activity in disease progression is worthy of further study to investigate possible mechanistic links.

Mannan-Binding lectin in asthma and allergy

Mannan-binding lectin (MBL) is a vital and versatile component of innate immunity. It is present in serum and may bind to a plethora of microbial pathogens and mediate opsonization of these by complement-dependent and/or independent mechanisms. Low-MBL levels in serum, attributed to certain genetic polymorphisms, constitute a major factor predisposing to several infectious diseases. However, recent studies propose that MBL extends beyond its classic role as a first-line host-defense molecule to a modulator of inflammation. In this review, we summarize and explore this potential and a possible novel role of MBL in asthma and allergy.

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin

Decreased sensing of the innate immune system may lead to chronic activation of the inflammatory cascade. We hypothesised that mannan-binding lectin (MBL) deficiency may confer risk of obesity and insulin resistance. We performed a cross-sectional study of MBL protein concentration (n=434) and MBL2 gene mutations (exon 1) (n=759) in association with obesity, markers of inflammation and insulin action (euglycaemic clamp, n=113), and a longitudinal study of MBL protein before and after weight loss in obese patients (n=10). We also studied the effects of MBL in vitro in muscle cells and circulating MBL-A (mouse equivalent of human MBL) in a mouse model. Among 434 consecutive non-diabetic men, the age-adjusted serum MBL concentration was lower in obese subjects than in lean subjects (median: 959 microg/ml [interquartile range: 116.8-2,044 microg/ml] vs 1,365 [467-2,513] microg/ml; p=0.01) and was accompanied by increased serum inflammatory markers. Insulin action correlated significantly with serum MBL (r=0.49, p<0.0001). Serum MBL concentration increased by a median of 110.2% after weight loss. The change in serum concentration of MBL was positively associated with the increase in insulin sensitivity (r=0.713, p=0.021). At least one MBL2 gene mutation was present in 48.2% of obese vs 39.3% of non-obese subjects (p=0.037). The plasma concentration of MBL-A was lower in insulin-resistant obese ob/ob mice, as was the glucose/insulin ratio. Incubation of rat soleus muscle with human MBL markedly increased fatty acid oxidation. These findings suggest that MBL, previously thought only to be involved in inflammation and immune system function, affects metabolic pathways.

Preoperative mannan-binding lectin pathway and prognosis in colorectal cancer.

Deficiency of the mannan-binding lectin (MBL) pathway of innate immunity is associated with increased susceptibility to infections. In patients with colorectal cancer (CRC), postoperative infection is associated with poor prognosis. The aim of the present study was to evaluate (1) the relation between the MBL pathway and postoperative infectious complications and survival of patients resected for CRC, and (2) the role of MBL in acute phase response compared to C-reactive protein (CRP). Preoperative MBL concentration, MBL-associated serine protease (MBL/MASP) activity and CRP were determined in serum from 611 patients and 150 healthy controls. The patients were observed for 8 years. Postoperative infections, recurrence and survival were recorded. The MBL pathway components were increased in the patients compared with the healthy controls (p < 0.0001). Low MBL levels were predictive of pneumonia (p = 0.01), and pneumonia (n = 87) was associated with poor survival (p = 0.003; HR = 1.5; 95% CI, 1.1 to 1.9). MBL and MBL/MASP activity showed no correlation with CRP (Spearman's rho = 0.02; 95% CI, -0.06 to 0.10). Low preoperative MBL levels are predictive of pneumonia, which is associated with poorer survival. MBL concentration and MBL/MASP activity was not predictive of other postoperative infections or long-term prognosis, and showed no correlation with CRP.

The potential role of mannan-binding lectin in the clearance of self-components including immune complexes.

Mannan-binding lectin (MBL) is a pattern recognition receptor in the innate immune system. It recognizes certain sugar residues arranged in a pattern that enables MBL to bind with sufficient strength. Such sugar patterns are common on the surface of many microorganisms, and MBL has therefore been considered to be an agent that can discriminate between self and nonself. There is, however, increasing evidence supporting that MBL, like many membrane-bound C-type lectin-like receptors, also helps to dispose of various outworn or abnormal body components. Most self-components are protected with sialic acid or galactose that disrupt the pattern of the sugars that MBL can bind, but MBL may be significantly involved in the elimination of self-components that have lost these protective terminal residues. The role of MBL in the clearance of invading pathogens has previously been thoroughly reviewed. Here, we review some findings that support the notion that MBL may contribute to noninflammatory removal of immune complexes and abnormal cells by the reticuloendothelial system. Defects in this clearance mechanism may cause an accumulation of potentially dangerous self-components, thereby increasing the likelihood of chronic inflammation and autoimmunity.

Preoperative Mannan‐Binding Lectin Pathway and Prognosis in Colorectal Cancer

Background: Deficiency of the mannan‐binding lectin (MBL) pathway of innate immunity leads to increased susceptibility to infections. In patients with colorectal cancer, postoperative infection is associated with poor prognosis. The aim of the present study was to evaluate (1) the relation between the MBL pathway and postoperative infectious complications and survival of patients resected for colorectal cancer and (2) the role of MBL as acute phase reactant compared to CRP. Methods: Preoperative MBL concentration, MBL/MBL‐associated serine protease (MASP) activity and CRP were determined in serum from 611 patients and 150 healthy controls. The patients were observed for 8 years. Postoperative infections, recurrence and survival were recorded. Results: The MBL pathway components were increased in the patients (P < 0.0001) compared to healthy controls. Low MBL levels were predictive of pneumonia (P = 0.01), and pneumonia (n = 87) was associated with poor survival (P = 0.003, HR = 1.5, 95% CI 1.1–1.9). MBL and MBL/MASP activity could not predict postoperative overall infections. MBL showed no correlation (spearman's ρ = 0.02, 95% CI −0.06–0.10) with CRP. Conclusions: Low preoperative MBL levels are predictive of pneumonia, which is associated with poorer survival. MBL concentration and MBL/MASP activity was not predictive of other postoperative infections or long‐term prognosis. MBL apparently is not a surrogate measure of CRP.

Elevated levels of mannan-binding lectin in patients with type 1 diabetes.

The hepatic protein mannan-binding lectin (MBL) activates the complement system on binding to carbohydrate patterns and is involved in first-line defense against invading microorganisms. Emerging evidence indicates that in some situations MBL may cause inexpedient complement activation and tissue injury through binding to endothelial glycosylations. MBL levels are suppressed by insulin treatment in critically ill patients, and, hypothetically, hepatic portal hypoinsulinemia could lead to increased levels of MBL in patients with type 1 diabetes. We measured MBL and C-reactive protein (CRP) levels in 132 normoalbuminuric type 1 diabetic patients and 66 healthy age- and sex-matched controls. The median MBL concentration was higher in diabetic patients than in healthy controls [1290 micro g/liter (interquartile range, IQR 354-2961 micro g/liter) vs. 970 micro g/liter (IQR 277-1607 micro g/liter), P = 0.025], whereas CRP concentrations were similar among patients and controls [1.42 mg/liter (IQR 0.95-2.21) vs. 1.21 mg/l (IQR 0.74-2.13), NS]. In diabetic subjects, CRP levels correlated with poor glycemic control as indicated by hemoglobin A(1c) and daily insulin dose, which was not the case with MBL. MBL concentrations were positively correlated with urinary albumin excretion (r = 0.22; P = 0.013) and increased with increasing urinary albumin excretion tertile (P = 0.036). In conclusion, our data demonstrate that circulating MBL concentrations are significantly elevated in patients with type 1 diabetes and suggest a possible role of MBL in the pathogenesis of renovascular complications in diabetes.

Immunohistochemical investigation of the tissue distribution of mannan-binding lectin in non-infected and virus-infected chickens.

This paper describes the results of immuno-histochemical staining for chicken mannan-binding lectin (MBL) in formalin-fixed tissue sections from non-infected chickens, and from chickens infected with infectious laryngotracheitis virus (ILTV) or infectious bursal disease virus (IBDV). In the non-infected chickens, MBL was detected in the cytoplasm of a few hepatocytes and in the germinal centres of the caecal tonsils, whereas sections of kidney, heart muscle, spleen, cerebrum, thymus, adrenal gland, bursa of Fabricius, bone marrow and trachea were without staining. In the ILTV-infected chickens, an intense staining reaction for MBL was detected in the cytoplasm of all hepatocytes and on the surface of, and inside, ILTV-infected cells. Also in the IBDV-infected chickens, an intense staining reaction for MBL was detected in the cytoplasm of all hepatocytes. No staining was seen in the follicles of the bursa of Fabricius, but MBL was present in non-identified cells in the interstitium, and in the cytoplasm of macrophage-like cells, located peripheral to the ellipsoid of the spleen. These findings indicate the liver as the primary site of MBL synthesis, and points to up-regulation as a result of the viral infections. The location outside the liver could indicate a role of MBL in the immune defence.

Role of Complement and Antibodies in the Control and Facilitation of HIV Disease.

In humans the HIV infection results in a chronic disease with a permanent fight between factors controlling HIV and the escape of the virus. Fromthese control mechanisms the present review summarizes the role betwen complement and autoantibodies; the competition of complement and anti-HIV antibodies for binding sites, the role of mannan-binding lectin in the susceptibility to and in the survival after HIV infection, the contribution of complement-dependent enhancing type antibodies to the clinical progression of HIV disease as well as the changing pattern of some autoantibodies (mimicking MHC class II molecules, anti-heat shock protein 60 antibodies and anti-C1q antibodies) which were found to correlate to immunological and clinical parameters.

Serum mannan-binding lectin (MBL) in patients with infection: clinical and laboratory correlates.

In this study, we determined the serum levels of mannan-binding lectin (MBL) in patients with suspected or documented infection to characterize the possible role of MBL in the susceptibility to infection. We also investigated the kinetics of MBL during the infection and correlated the concentrations of MBL with those of acute-phase reactants C-reactive protein (CRP) and group II phospholipase A2 (PLA2-II) and cytokines interleukin-1(IL-1). interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). The frequency of MBL deficiency in the patients with signs of infection did not differ from that of controls. In four patients with MBL deficiency, the infections were caused by common pathogens and the outcome was normal. The mean MBL concentration in the patients with signs of infection was significantly higher than in the healthy controls (9.88 and 4.48 mg/l, respectively; p < 0.05). The highest mean MBL concentration was observed in patients with clinically or microbiologically documented bacterial infection. During follow-up, the MBL concentration altered individually in different patients, but no particular change in pattern in the MBL concentration could be demonstrated in any patient group. Of the acute-phase reactants in the circulation, only CRP and IL-1 showed a weak, albeit significant, negative correlation with the concentration of MBL. In conclusion, the deficiency of MBL was not shown to be an independent risk factor for infection in the adult population studied. The concentration of MBL did not follow the change in pattern of other acute-phase reactants and cytokines during the acute phase response. Therefore, measurement of the MBL concentration as an acute-phase reactant is not useful in the diagnosis or follow-up of infection. On the other hand, the deficiency of MBL can be detected reliably by serological methods even during an infection.