Serum Mannose-binding Lectin Levels Research Articles

Binding capacity of mannose-binding lectin (MBL) is associated with the severity of chronic Chagas cardiomyopathy

Chagas disease (CD) is a global problem. Currently, it affects approximately 15 million individuals in Latin America. It is well know that the human immune response is related to different clinical manifestations. Mannose binding lectin (MBL) plays an important role in innate immunity, and it mediates the phagocytosis and complement-mediated destruction of pathogens. The binding capacity is enhanced by the oligomerization of MBL. In this study, we evaluated the serum concentration and the binding capacity of MBL in patients with chronic chagasic cardiomyopathy. A total of 77 patients with chronic CD were included with indeterminate (n = 19), mild cardiac (n = 29) and severe cardiac (n = 29) forms. The serum concentration and the binding capacity were measured using enzyme-linked immunosorbent assays (ELISA). There was no significant difference in the serum MBL levels between the groups of patients. However, we found a relationship between the binding capacity and the groups studied. Our results suggest that binding capacity of MBL could be an indicator of clinical manifestation in Chronic Chagas cardiomyopathy. Furthermore, combined with the Mannose Binding Index results in a useful clinical tool for management of Chronic Chagas Patients.

Mannose-Binding Lectin Gene Polymorphism and Its Association with Susceptibility to Recurrent Vulvovaginal Candidiasis.

Recurrent vulvovaginal candidiasis (RVVC) is a common illness influencing childbearing women worldwide. Most women suffering from RVVC develop infection without specified risk factors. Mannose-binding lectin (MBL) is an important component of innate immune defense against Candida infection. Innate immunity gene mutations and polymorphisms have been suggested to play a role in susceptibility to RVVC. This study aimed to investigate the association between MBL 2 gene exon 1 codon 54 polymorphism and susceptibility to RVVC in childbearing women. Whole blood and serum samples were obtained from 59 RVVC cases and 59 controls. MBL serum level was measured by enzyme-linked immune-sorbent assay (ELISA). MBL2 exon 1 codon 54 polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). It was shown that MBL serum level was nonsignificantly different between RVVC cases and controls. The risk of RVVC was 3 times higher in those carrying MBL2 exon 1 codon 54 variant allele (B). It could be concluded that the carrying of MBL2 exon 1 codon 54 variant allele (B) was shown to be a risk factor for RVVC in childbearing women.

Circulating levels of mannose-binding lectin (MBL) in age-related macular degeneration.

To assess whether the serum levels of mannose-binding lectin of the lectin complement pathway are associated with age-related macular degeneration. Patients with age-related macular degeneration and age-matched controls underwent full ophthalmologic examination and optical coherence tomography. Using a time-resolved immunofluorometric assay, blood samples were evaluated to determine the serum mannose-binding lectin levels. A total of 136 individuals were evaluated, including 68 patients with age-related macular degeneration (34 exudative and 34 nonexudative) and 68 age-matched controls. The median mannose-binding lectin level was 608 ng/mL (range, 30-3,415 ng/mL) in patients with age-related macular degeneration and 739 ng/mL (range, 30-6,039 ng/mL) in controls, with no difference between the groups. Additionally, the median mannose-binding lectin level was 476 ng/mL (range, 30-3,415 ng/mL) in exudative cases and 692 ng/mL (range, 30-2,587 ng/mL) in nonexudative cases. Serum mannose-binding lectin levels were not associated with age-related macular degeneration or with the exudative and nonexudative forms of the disease.

The Role of Mannose-Binding Lectin Serum Level in Tubotympanic Chronic Suppurative Otitis Media.

Background Chronic suppurative otitis media (CSOM) is a common public health problem worldwide and a major cause of hearing impairment especially in developing countries. The role of Mannose-Binding Lectin (MBL), a component of innate immunity, in CSOM has not been studied. The aim of the study was to examine whether MBL deficiency was more frequently present in cases group of tubotympanic CSOM patients rather than healthy subjects. Material and Methods This was an analytic observational study. Subjects were enrolled in the Otorhinolaryngology Clinic at Margono Soekarjo Hospital, Purwokerto, Indonesia. An independent t-test was used to compare the mean of MBL serum concentration between tubotympanic CSOM subjects and control. Results From 36 tubotympanic CSOM patients, there were 8 (22.22%) patients with MBL deficiency (MBL level < 100 ng/ml), while no deficiency was found in the control group. The mean of MBL level in cases group was 354.88 ng/ml, with the lowest level being 0.001 ng/ml and the highest level 690.24 ng/ml, while in the control group MBL level mean was 376.27 with the lowest level being 188.71 and the highest level 794.54 ng/ml. Conclusion There was no significant difference of MBL serum level between tubotympanic CSOM and control group. However, the presence of subjects with MBL deficiency in the tubotympanic CSOM group might be considered as playing a role in the tubotympanic CSOM.

Serum mannan-binding lectin in patients with pulmonary tuberculosis: Its lack of a relationship to the disease and response to treatment.

Background: Lectin pathway mediates complement activation, which is activated by many microorganisms. This study aimed at determining the serum levels of mannose-binding lectin (MBL) in patients with pulmonary tuberculosis, assessing its relationship to antiuberculosis treatment response, and comparing them with a control group. Methods: This cross-sectional study was conducted on patients with pulmonary tuberculosis during 2012 and 2013 in South West of Iran. PPD-ST-negative individuals were selected as controls from healthy relatives of patients. Serum MBL levels were measured using ELISA kit (Human MBL HK323, Hycultbiotech Company, Netherlands). All patients were followed- up for response to treatment. We applied Mann-Whitney and Fisher’s exact tests and used SPSS Version 17 software for statistical analysis. Results: The study included 62 patients as the case group and 63 noninfected TB patients as the control group. The MBL (ng/mL) in patients with pulmonary tuberculosis (median = 1012) was significantly (p= 0.037) higher than that of the control group (median= 296.2). No significant difference was found in the MBL level (ng/mL) between patients with response to antituberculosis treatment (median= 1012) and patients with treatment failure (median= 798.9) (p= 0.84). Conclusion: MBL may be involved in the pathogenesis of tuberculosis and in the low values that are protective against tuberculosis, and it seems that it has no effect on the antituberculosis treatment response.

Prospective Observational Study on the Association Between Serum Mannose-Binding Lectin Levels and Severe Outcome in Critically Ill Patients with Pandemic Influenza Type A (H1N1) Infection.

BackgroundMannose-binding lectin (MBL) plays an important role in the innate immune response. In addition to activating the complement, MBL can induce cytokine production and contribute to a deleterious inflammatory response with severe A(H1N1)pdm09 virus infection. Our aim was to determine if serum MBL levels correlate with the risk of mortality in intensive care units (ICU) patients with A(H1N1)pdm09 infection.MethodsProspective observational study was performed in ICU patients with acute respiratory distress syndrome due to influenza A(H1N1)pdm09 virus. Demographic characteristics and severity indices were recorded at ICU admission. MBL was assayed from blood drawn at influenza diagnosis within 24–48 h following the ICU admission. Outcomes were compared according to MBL levels. Results are expressed as median and interquartile range.ResultsSerum MBL levels were studied in 27 patients (age: 56 [IQR 29] years) with severe A(H1N1)pdm09 infection and in 70 healthy controls. Median admission SAPSII and SOFA scores were 49 [IQR 26] and 12 [IQR 5], respectively. Mortality rate after a 30-day was 37%. MBL was significantly higher in non-survivors (3741 [IQR 2336] ng/ml) vs survivors (215 [IQR 1307] ng/ml), p = 0.006, as well as control group (1814 [IQR 2250] ng/ml), p = 0.01. In contrast, MBL levels in survivors group were significantly lower than the controls group (215 [IQR 1307] ng/ml vs. 1814 [IQR 2250] ng/ml, p = 0.005). MBL cut-off > 1870 ng/ml had a sensitivity of 80% and a specificity of 88.2% for mortality [AUC = 0.82 (95% CI 0.63–0.94)]. Kaplan–Meier analysis demonstrated a strong association between MBL levels and mortality (log-rank 7.8, p = 0.005). MBL > 1870 ng/ml was independently associated with mortality (HR = 8.7, 95% CI 1.2–29.1, p = 0.007).ConclusionsThis study shows that baseline MBL > 1870 ng/ml is associated with higher mortality in ICU patients with severe A(H1N1)pdm09 infection.

Mannose-binding lectin (MBL) deficiency and tuberculosis infection in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) patients may have higher prevalence of mannose-binding lectin (MBL) deficiency than normal individuals. MBL deficiency may influence susceptibility to infections. The aim of the study was to verify if MBL deficiency in patients with AS predisposes to infections. We studied 60 patients with AS diagnosed according to the Assessment of SpondyloArthritis international Society (ASAS) criteria. These patients had their MBL serum levels determinated. Twenty-five individuals were identified as MBL deficient (serum values 100ng/mL). These patients were paired with 35 "sufficient" MBL producers (median serum level=700ng/mL; range 150-4100ng/mL) for gender, age, use of medications, and tobacco exposure. Medical records of all patients were retrospectively investigated for the period of 5years and the rate of infection occurrence was compared in the two groups. AS patients with MBL deficiency had higher number of urinary tract infections (p=0.03; IRR=2.33; 95% CI=0.95-6.04) and tuberculosis (p=0.008; IRR=9.8; 95% CI=1.2-441.6) than controls. Regarding tuberculosis infection, one patient (2.8%) in the MBL-sufficient group and six (24.0%) from the deficient group had this infection. The MBL-sufficient patient and five from the deficient group have had latent infections, detected in the screening tests done previous to anti-TNF drug use. The other, in the deficient group, had lung infection while not on anti-TNF treatment. Another patient, from the deficient group, has had tuberculosis skeletal infection in the past. We found a significant association between MBL deficiency and higher risk of tuberculosis and urinary tract infection in patients with AS. More studies with higher number of patients are needed to confirm this finding.

Mannose-Binding Lectin-Deficient Donors Increase the Risk of Bacterial Infection and Bacterial Infection-Related Mortality After Liver Transplantation.

Mannose-binding lectin (MBL) is synthesized by the liver and binds to microbes. MBL2 gene polymorphisms produce intermediate/low/null or normal MBL serum levels (MBL-deficient or MBL-sufficient phenotypes, respectively). We aimed to evaluate the incidence and severity of infection, rejection, and survival within 1 year after liver transplantation (LT) according to donor and recipient MBL2 gene polymorphisms. A repeated-event analysis for infection episodes (negative binomial regression, Andersen-Gill model) was performed in 240 LTs. Four hundred twenty-eight infectious episodes (310 bacterial, 15 fungal, 65 cytomegalovirus [CMV]-related, and 38 viral non-CMV-related episodes) and 48 rejection episodes were recorded. The main bacterial infections were urinary (n = 82, 26%) and pneumonia (n = 69, 22%). LT recipients of MBL-deficient livers had a higher risk of bacterial infection (incidence rate ratio [IRR] 1.48 [95% confidence interval 1.04-2.09], p = 0.028), pneumonia (IRR 2.4 [95% confidence interval 1.33-4.33], p = 0.013), and septic shock (IRR 5.62 [95% confidence interval 1.92-16.4], p = 0.002) compared with recipients of MBL-deficient livers. The 1-year bacterial infection-related mortality was higher in recipients of MBL-deficient versus MBL-sufficient livers (65.8% vs. 56.1%, respectively; p = 0.0097). The incidence of rejection, viral, or fungal infection was similar in both groups. Recipient MBL2 genotype did not significantly increase the risk of bacterial infection. LT recipients of MBL-deficient livers have a higher risk of bacterial infection, pneumonia, septic shock, and 1-year bacterial infection-related mortality after LT.

Mannose-binding lectin serum levels in patients with systemic lupus erythematosus: association with thrombocytopaenia and seizure.

The complement system contributes to the pathogenesis of systemic lupus erythematosus (SLE). Mannose-binding lectin (MBL) is a key molecule of the lectin pathway of complement and seems to be related to the clinical manifestations of this disease. We evaluated the serum levels of MBL and its relationship with disease onset and clinical findings in SLE patients. Serum samples were analysed in 195 patients and 145 healthy controls from southern Brazil. Patients with high MBL levels (above 2000 ng/ml) showed a significant increase in the frequency of thrombocytopaenia ( p = 0.007; OR = 2.71; 95% CI = 1.32-5.55); and seizures ( p = 0.034; OR = 2.61; 95% CI = 1.07-6.37). A positive correlation between disease activity and MBL levels (>2000 ng/ml; p = 0.031, rho = 0.279) as well as of MBL concentration with accumulated organ damage ( p = 0.021; rho = 0.232) was observed. Our results suggest a role for MBL in the development of clinical manifestations such as thrombocytopaenia and seizures in SLE patients. These findings corroborate the participation of the lectin pathway of complement in the pathophysiologic mechanisms underlying clinical manifestations of SLE.

Serum Levels of Mannose-Binding Lectin in Atopic and Healthy Mongolian Adults

Objectives: Mannose-binding lectin (MBL) is a vital protein of an innate immune system synthesized by the liver. The serum level of MBL is associated with an increased susceptibility to infection with a high risk of allergic and autoimmune diseases. The aim of this study was to determine the profile of serum levels of MBL in atopic and healthy Mongolian subjects. Methods: Serum samples were collected from 219 healthy Mongolian adult blood donors and 216 atopic subjects. We analyzed the MBL level in each serum by using the double-antibody sandwich ELISA method. Results: The mean serum level of MBL was 3088.28 ± 669.8 ng/ ml in atopic subjects and 2165.07 ± 708.5 ng/ml in healthy groups. In males, the MBL mean serum level of atopic subjects was 3012.8 ± 783.16 ng/ml and 2073.33 ± 678.26 ng/ml in the healthy group of males. The MBL mean serum level of female atopic subjects was 3138.22 ± 580.6 ng/ml and 2263.61 ± 733.1 ng/ml in the healthy group of females. Low association and significant differences were observed between MBL levels of atopic and healthy subjects. Conclusion: The serum level of MBL in atopic subjects was comparatively higher than in subjects of the healthy group. Significant differences were observed between mean levels of MBL between the different age groups.

Low Serum Mannose Binding Lectin (MBL) Levels and -221 YX Genotype of MBL2 Gene Are Susceptible to Neonatal Sepsis in the Chinese Han Population

Background: The diagnosis of neonatal sepsis remains a challenge as the condition lacks early clinical signs and reliable biomarkers. Objectives: The aim of our study was to determine whether serum mannose binding lectin (MBL) levels and genotypes of MBL2 gene could be used as markers for predicting neonatal sepsis in the Chinese Han population. Methods: This prospective study was hospital-based in design. 48 neonates with clinical signs and symptoms of septicemia (study group), and 96 infants with no infection (control) were included. All the neonates are Chinese Han descent. MBL2 promoter polymorphisms at positions -550, -221 and +4 were analyzed by direct sequencing, and serum MBL levels were estimated by enzyme-linked immunesorbent assay. Results: Frequencies of genotype -221 YX were significantly higher in the study group (45.8%) compared with the control group (15.60%; P = 0.00009). The median serum MBL level was found to be significantly lower in infants who had the -221YX genotype (214.54 ng/mL) compared with those who had the -221YY genotype (597.85 ng/mL; P < 0.0001). Additionally, the median of serum MBL was significantly lower in infants with septicemia (289.65 ng/mL) than in controls (597.75 ng/mL; P = 0.041). According to ROC analysis, the cutoff value of MBL concentration ≤ 384.60 (ng/mL) had a sensitivity of 0.806 and a specificity of 0.777 for predicting sepsis. Conclusions: This study suggested that serum MBL and the -221 YX genotype of the MBL2 gene might be predisposed factors for sepsis in the Chinese Han population.

Mannose-binding lectin and l-ficolin polymorphisms in patients with community-acquired pneumonia caused by intracellular pathogens.

SummaryCommunity‐acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose‐binding lectin (MBL) and l‐ficolin (l‐FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Chlamydia species or Mycoplasma pneumoniae) compared with controls (P = 0·016). Furthermore, patients with these haplotypes were more often bacteraemic (P = 0·019). It can therefore be concluded that MBL2 and FCN2 polymorphisms are not major risk factors for CAP in general, but that the +6424G>T SNP in the FCN2 gene predisposes to C. burnetii pneumonia. In addition, patients with genotypes corresponding with high serum MBL levels are at risk for atypical pneumonia, possibly caused by enhanced phagocytosis, thereby promoting cell entry of these intracellular bacteria.

Serum level of mannose-binding lectin in cirrhotic patients with spontaneous bacterial peritonitis

Objectives To evaluate the role of mannose-binding lectin (MBL) in cirrhotic patients with and without spontaneous bacterial peritonitis (SBP) and to determine its role in the diagnosis of peritonitis. Background MBL deficiency increases the risk of various infections mostly in immunodeficient conditions. SBP is one of the bacterial infections causing morbidity and mortality under liver cirrhotic patients. Materials and methods A total of 90 individuals (66 male and 24 female with the mean age 52.55 ± 9.90 years) were included: 35 cirrhotic patients with ascites and SBP, 35 cirrhotic patients with ascites and no SBP and 20 apparently healthy persons as a control. The studied groups were subjected to full medical history, clinical examination and measurement of serum level of mannose-binding lectin (sr MBL) by enzyme-linked immunosorbent assay. Cirrhotic patients were subjected to liver function tests, and biochemical and bacteriological examination of ascitic fluid including culture and sensitivity testing was performed for all cirrhotic patients with ascetic fluid total leucocytic count (TLC) greater than 500 cells/mm3. Results sr MBL was significantly lower in group 1 than in group 2 (P Conclusion sr MBL could be considered as a predictive marker for SBP in cirrhotic patients.

Mannose-Binding Lectin Does Not Act as a Biomarker for the Progression of Preinvasive Lesions of Invasive Cervical Cancer

Objective: To evaluate serum concentrations of mannose-binding lectin (MBL) in women presenting with different human papillomavirus (HPV)-associated cervical lesions. Subjects and Methods: A total of 364 women, who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital (HEG), Curitiba, Brazil, were enrolled in the study. Based on the latest cervical colposcopy-guided biopsy results, the women were divided into 4 groups: cervical intraepithelial neoplasia CIN-I (n = 54), CIN-II (n = 72), CIN-III (n = 145), and invasive cancer (n = 93). A time-resolved immunofluorometric assay was used to measure the MBL concentrations in serum. The statistical analysis was done using GraphPad Prism 6.0. Comparisons were performed by Kruskal-Wallis and Mann-Whitney tests and analyzed by χ² test; continuous variables are presented as medians and categorical variables as frequencies. Results: The median MBL concentrations in decreasing order were as follows: invasive cancer: 1,452 ng/mL, CIN-I: 1,324 ng/mL, CIN-II: 1,104 ng/mL, and CIN-III 1,098 ng/mL. However, no statistical significance was found among the 4 groups with HPV-associated lesions (p = 0.11). Equally, the MBL levels did not show a significant association between the age of the patients and the severity of the cervical lesions (p = 0.68). No statistical significance was found in the median values of MBL or in the status of MBL deficient (<100 ng/mL) and high producers (>1,000 ng/mL) among the women in each group (p = 0.77). Conclusion: In this study, there was no statistically significant difference in MBL serum levels among the groups with CIN. Hence MBL serum concentration appeared not to have influenced the progression of HPV-related preinvasive cervical lesions into invasive cancer.

Mannose-Binding Lectin Deficiency in Brazilian Patients with Spondyloarthritis

ABSTRACTBackground: Infections are usually involved in the pathogenesis of spondyloarthritis (SpA). Mannose-binding lectin (MBL) is a component of the innate immune system with an important role in microbial defense.Objective: To study the prevalence of MBL deficiency in SpA patients as well as its influence in the clinical profile of these diseases.Methods: We studied 89 SpA patients and 89 healthy individuals, paired for age and gender. MBL serum levels were measured by ELISA test. Individuals with levels ≤100 ng/mL were considered deficient. SpA patients had determination of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, Bath Ankylosing Spondylitis Functional Index (BASFI), C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and review of their clinical profile.Results: SpA patients had MBL levels ranging from 100 to 4100 ng/mL (median = 375 ng/mL); controls levels ranged from 100 to 4703 ng/mL (median = 1204 ng/mL; p < 0.0001). The prevalence of MBL deficiency was 27/89 (30.3%) in SpA patients and 12/89 (13.5%) in controls, with p = 0.01; OR = 2.5 (95% IC = 1.2–5.3). No association/correlation was found between MBL levels with BASDAI, BASFI, age at disease onset, ASDAS-CRP, ESR, CRP, presence of uveitis, HLAB27, peripheral arthritis, or SpA subtype (all p = NS).Conclusion: MBL levels may be linked with the occurrence of SpA but do not influence its phenotype.

Evaluation of Mannose-Binding Lectin is a Useful Approach to Predict the Risk of Infectious Complications Following Autologous Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) associated immunocompromised state carries high risk of infectious complications. Mannose-binding lectin (MBL) is an acute phase protein involved in innate immune response. Serum MBL level is genetically determined and quite stable. According to literature, significant association was shown between low MBL concentrations and serious infections. The association between serum MBL level and frequency and severity of infections was studied in 186 patients following autologous HSCT. Double-monoclonal antibody sandwich enzyme-linked immunosorbent assay was used to determine MBL antigen level in sera. MBL levels were measured around 100 days following transplantation, in a period without active infection. Twenty-one patients (11%) were MBL deficient. The median time of first infection and number of infections during the first year post-transplantation were not significantly different between patients with MBL deficiency and those without MBL deficiency. The occurrence and number of infections after HSCT correlated with the MBL/C-reactive protein ratio. The number of severe infections was not higher among those with MBL deficiency. The occurrence of infections after the pre-engraftment period during the first year post-transplantation was significantly different in patient groups separated by MBL cut-off level. The MBL/C-reactive protein ratio might be a useful marker of infectious complications. MBL measurement may be helpful in antibiotic treatment. In case of MBL deficiency, earlier and more intensive treatment may be indicated.

Early Changes of Mannose-Binding Lectin, H-Ficolin, and Procalcitonin in Patients with Febrile Neutropenia: A Prospective Observational Study.

Objective:The significance of mannose-binding lectin (MBL) and H-ficolin deficiency in febrile neutropenic (FN) patients and the correlation of these markers along with consecutive C-reactive protein (CRP) and procalcitonin (PCT) levels during the infectious process are investigated.Materials and Methods:Patients with any hematological malignancies who were defined to have “microbiologically confirmed infection”, “clinically documented infection”, or “fever of unknown origin” were included in this single-center prospective observational study. Serum levels of CRP, PCT, MBL, and H-ficolin were determined on 3 separate occasions: at baseline (between hospital admission and chemotherapy), at the onset of fever, and at the 72nd hour of fever.Results:Forty-six patients (54% male, mean age 41.7 years) with 61 separate episodes of FN were evaluated. Eleven patients (23.9%) had “microbiologically confirmed infection”, 17 (37%) had “clinically documented infection”, and 18 (39.1%) had “fever of unknown origin”. Fourteen (30.4%) patients had low (<500 ng/mL) initial MBL levels and 7 (15.21%) had low (<12,000 ng/mL) H-ficolin levels. Baseline MBL and H-ficolin levels did not significantly change on the first and third days of fever (p=0.076). Gram-negative bacteremia more frequently occurred in those with low initial MBL levels (p=0.006). PCT levels were significantly higher in those with microbiologically documented infections. Mean and median PCT levels were significantly higher in cases with bacteremia. There was no significant difference between hemoculture-positive and-negative patients in terms of CRP levels.Conclusion:Monitoring serum H-ficolin levels was shown to be of no benefit in terms of predicting severe infection. Low baseline MBL levels were correlated with high risk of gram-negative bacteremia; however, no significant correlation was shown in the follow-up. Close monitoring of PCT levels is warranted to provide more accurate and specific data while monitoring cases of bacteremia.

Association study between mannose-binding lectin haplotypes and X gene mutation of hepatitis B virus from treatment naïve patients.

Mannose binding lectin (MBL) plays important role in the innate immunity of human. Mutations in the MBL2 gene can significantly change the serum level of MBL, and consequently alter the susceptibility and progression of infectious disease. However, the association between the MBL2 profile and the HBV mutation and quasispecies complexity has not yet been reported. Our approach includes the study of the MBL2 gene genotype as well as ultra-deep sequencing of the HBV viruses obtained from the plasma of 50 treatment naïve patients with chronic HBV infection. We found that the liver function was better among patients within the high MBL2 group with respect to those within the medium/low MBL2 group. Likewise, the number of mutations in the HBV X gene as well as the viral quasispecies complexity were significantly higher in medium/low MBL2 production group. Nucleotide substitution rates were also higher within the medium/low MBL2 production group in all positions described to have an influence in liver cancer development, except for A1499G. In this work we show that the MBL2 profile may have an impact on the HBV X gene mutations as well as on viral quasispecies complexity.

Association of MBL With Work-Related Respiratory Symptoms in Bakery Workers.

Baker's asthma is the most prevalent occupational asthma, and IgE-mediated response is known as a major pathogenesis. However, recent studies have suggested the involvement of innate immune response because wheat flour contains bacterial endotoxins or lipopolysaccharides. To further understand a role of innate immune response in the development of work-related respiratory symptoms (WRS) in bakery workers, we investigated mannose-binding lectin (MBL), one of the initiating components of the complement cascade in a single cohort of bakery workers. A total of 373 bakery workers completed a questionnaire regarding WRS. The bakery workers were divided into 2 groups according to previous history of allergic rhinitis (AR)/bronchial asthma (BA): those with history of AR/BA (group I) and those without (group II). We measured serum MBL levels by using enzyme-linked immunosorbant assay and genotyped 4 single nucleotide polymorphisms of the MBL2 gene (226G>A in exon 1, -554G>C, -431A>C, and -225G>C in the promoter) by using TaqMan assays. Fifty-nine subjects (15.5%) were previously diagnosed with AR/BA, and 64 subjects (16.8%) complained of WRS. No significant differences were found in serum MBL levels between groups I and II. However, in group II subjects, but not in group I subjects, the serum MBL levels were significantly higher in bakery workers with WRS than in those without. In addition, the serum MBL levels were significantly different according to genetic polymorphisms of the MBL2 gene and its haplotypes. In conclusion, serum MBL, affected by genetic polymorphisms, may be associated with WRS in bakery workers with no previous history of AR/BA.

Mannose-binding lectin gene (MBL2) polymorphisms related to the mannose-binding lectin low levels are associated to dengue disease severity

Dengue is the main arbovirosis in the tropical and subtropical areas of the world. The majority of infected individuals present an asymptomatic outcome while others progress to dengue fever (DF) or dengue haemorrhagic fever (DHF). Dengue infection evolution to severe outcomes is in part, related to innate immunity response. The MBL2 gene encodes for a pathogen recognition pattern molecule, the mannose-binding lectin (MBL). Variant alleles at promoter and structural regions of the MBL2 are related to serum MBL levels and function. Due to the important inflammatory modulation role of MBL, MBL2 polymorphisms could influence dengue progression. Therefore, this study investigated associations of MBL2 polymorphisms and serum MBL levels in patients with dengue. Genotyping of promoter and structural regions of MBL2 was performed by real-time PCR using Taqman® probes in 161 patients presenting DF or DHF outcome. For the serum MBL determination a commercial ELISA kit was used. The variant OO genotype and O allele were associated with DHF (p=0.008 and p=0.009 respectively). Haplotypes correlated to MBL low levels were associated with DHF (p=0.04). Our results support the hypothesis that patients carrying genotypes or haplotypes of low production of MBL would be more susceptible to DHF.