Low Mannose-binding Lectin Levels Research Articles

Strong predictive value of mannose-binding lectin levels for cardiovascular risk of hemodialysis patients

BackgroundHemodialysis patients have higher rates of cardiovascular morbidity and mortality compared to the general population. Mannose-binding lectin (MBL) plays an important role in the development of cardiovascular disease. In addition, hemodialysis alters MBL concentration and functional activity. The present study determines the predictive value of MBL levels for future cardiac events (C-event), cardiovascular events (CV-event) and all-cause mortality in HD patients.MethodsWe conducted a prospective study of 107 patients on maintenance hemodialysis. Plasma MBL, properdin, C3d and sC5b-9 was measured before and after one dialysis session. The association with future C-events, CV-events, and all-cause mortality was evaluated using Cox regression models.ResultsDuring median follow-up of 27 months, 36 participants developed 21 C-events and 36 CV-events, whereas 37 patients died. The incidence of C-events and CV-events was significantly higher in patients with low MBL levels (<319 ng/mL, lower quartile). In fully adjusted models, low MBL level was independently associated with increased CV-events (hazard ratio 3.98; 95 % CI 1.88–8.24; P < 0.001) and C-events (hazard ratio 3.96; 95 % CI 1.49–10.54; P = 0.006). No association was found between low MBL levels and all-cause mortality. Furthermore, MBL substantially improved risk prediction for CV-events beyond currently used clinical markers.ConclusionsLow MBL levels are associated with a higher risk for future C-events and CV-events. Therefore, MBL levels may help to identify hemodialysis patients who are at risk to develop cardiovascular disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0995-5) contains supplementary material, which is available to authorized users.

Host genetics and susceptibility to congenital and childhood cytomegalovirus infection: a systematic review.

AimTo summarize available evidence on the role of host genetics in the susceptibility to congenital and childhood cytomegalovirus (CMV) infections by conducting a systematic review of published studies.MethodsWe searched online databases (PubMed, Web of Science, Scopus and HuGe Navigator) for relevant studies with well-defined inclusion and exclusion criteria and assessed the risk of bias using novel Confounding-Selection-Information bias score (CSI).Results5105 studies were initially identified, but only 5 met all the inclusion criteria and were analyzed in detail. Polymorphisms of the toll-like receptors (TLRs) and mannose-binding lectin (MBL) genes were shown to have an impact on the CMV infection in infants. Polymorphisms of the TLR2 (rs3804100, rs1898830), TLR4 (rs4986791), and TLR9 (rs352140) were shown to have a role in congenital CMV infection. Low MBL levels were associated with CMV infection in Chinese individuals, a finding that was not replicated in Caucasians. The overall credibility of evidence was weak.ConclusionsBased on currently available very limited amount of evidence, it is uncertain whether congenital and childhood CMV infections are under host genetic control. Additional primary studies are needed with more specific research hypotheses that will enable gradual understanding of specific mechanisms of the CMV pathogenesis. More genetic studies in the future will facilitate better understanding of host susceptibility and likely enable novel preventative and curative measures.

Mannose binding lectin polymorphisms in systemic lupus erythematosus in Spain

Low mannose binding lectin (MBL) producer genotypes have been considered as a systemic lupus erythematosus (SLE) risk factor. The aim of this study was to explore whether polymorphisms in the MBL gene are associated with susceptibility to SLE and disease-specific clinical manifestations or with disease severity in SLE patients in Son Llàtzer Hospital. MBL2 exon 1 and promoter polymorphisms were genotyped and MBL plasma levels were quantified by ELISA in 39 SLE cases and in 96 healthy controls. High MBL producer genotypes HYPA and LXPA were the most frequent haplotypes (65 and 62 participants, respectively). LYQC/HYPD, LXPA/LYQC and LYPB/HYPD were only found in SLE, and all of them were related to severe MBL deficiency. SLE patients showed a trend towards more severe MBL deficiency (MBL &lt;100 ng/mL) compared to controls (10 [25.6%] and 11 [11.46%] respectively, P = 0.07). The wild-type genotype was more frequent in controls compared to SLE. The trend towards more severe MBL deficiency in SLE and the fact that some of the low-MBL producer genotypes were only found in SLE patients, suggest that low MBL levels or MBL2 variant could be a risk factor for the development of SLE.

Second-trimester plasma mannose-binding lectin levels and risk of preterm birth

Objective: To investigate whether mannose-binding lectin (MBL) gene polymorphisms and low levels of second-trimester plasma MBL were significant risk factors for preterm birth in Taiwanese women.Methods: We conducted a prospective longitudinal study to explore the associations of MBL2 gene single nucleotide polymorphisms and plasma MBL levels between preterm birth and term controls. Blood samples were collected at 16–23 weeks of gestation, and were divided into 51 mothers with preterm births and 255 term controls after delivery. Blood samples were further collected at delivery from 11 mothers with term delivery and 9 with preterm births. DNA was isolated, and polymorphisms in exon 1, the promoter untranslated regions of MBL2 were determined by polymerase chain reaction. The plasma concentrations of MBL were measured by enzyme-linked immunosorbent assay.Results: There is a positive correlation between SNP genotypes and second-trimester plasma MBL levels. Among mothers with preterm births, a higher frequency of specific genotypes with low MBL levels was not observed. The second-trimester plasma MBL levels were not significantly different between mothers with preterm births (N = 51) and term deliveries (N = 255). However, among mothers (N = 11) with term pregnancies, the MBL plasma level significantly increased from the second trimester to delivery, whereas in mothers (N = 9) who developed preterm delivery, the MBL level did not significantly change.Conclusion: Genotypes associated with low levels of plasma MBL during pregnancy did not increase the risk of preterm births. A low second-trimester plasma MBL level is therefore not a predictor for the development of preterm birth.

Low levels of mannose-binding lectin at admission increase the risk of adverse neurological outcome in preterm infants: a 1-year follow-up study

Objective: The aim of this study was to explore the association between serum levels of mannose-binding lectin (MBL) at admission and neurodevelopmental outcomes in a group of Chinese preterm infants, observed prospectively, until 1-year of corrected age (CA).Methods: All preterm infants used in this study were received from the neonatal intensive care unit (NICU) of our Hospital between 1 January 2012 and 31 August 2013. Serum levels of MBL and clinical data were obtained at the time of admission. The influence of MBL levels on neurological outcome was assessed by logistic regression analysis. Clinical follow-up was performed at 1 year.Results: The study cohort consisted of 175 neonates at baseline and 105 finished the 1-year follow-up. The mean serum MBL levels at the time of admission were significantly lower in children with adverse neurological outcomes as compared with children with no adverse [0.53 (SD = 0.09) μg/ml versus 0.80 (SD = 0.17) μg/ml, respectively; t = 8.342, p < 0.0001]. In multivariate analysis, there was an increased risk of adverse neurological outcomes associated with MBL ≤ 0.68 μg/ml [odds ratios (OR) = 12.11, 95% confidence interval (CI): 2.31–30.32; p < 0.0001] after adjusting for possible factors.Conclusion: Preterm infants who had low levels of MBL at admission are exposed to an increased risk of adverse neurological outcomes.

No Strong Relationship Between Components of the Lectin Pathway of Complement and Susceptibility to Pulmonary Tuberculosis.

Mycobacterium tuberculosis (TB) may utilise the lectin complement pathway to facilitate entry into its niche within macrophages. Previous studies examining mannose-binding lectin (MBL) in patients with TB have been limited by failure to correlate genotype/phenotype relationships. This study investigated serum levels and genotypes of MBL, Ficolin-2, Ficolin-3 and MASP-2 in 168 patients with pulmonary tuberculosis and 168 age/sex-matched controls. Low serum levels of MBL and Ficolin-2 were defined using cut-offs previously identified in the literature. Median MBL serum levels were higher in TB patients than controls-1400ng/ml (IQR 435-2520) vs 1030ng/ml (350-2050), p = 0.02-but this was not mirrored by a difference in MBL haplotype frequencies (MBL deficient haplotypes were observed in 11.9% of TB patients and 11.3% of controls). Severe Ficolin-2 deficiency (<1200ng/ml) was more frequent in TB than controls (7.1 vs 3.0%, odds ratio 2.51 95% CI 0.86-7.28, p = 0.1) but the difference was not statistically significant. No relationship between Ficolin-2, Ficolin-3 or MASP-2 genotypes or serum levels and TB were observed. No strong relationship between the lectin complement pathway and pulmonary tuberculosis was observed. Previous data linking high MBL serum levels with TB were likely due to an acute phase response rather than a true effect on disease susceptibility.

Effects of mannose-binding lectin and mannose-binding lectin polymorphisms on treatment response in patients with chronic hepatitis C.

The natural course and clinical outcome of hepatitis C virus (HCV) infection is related to the interaction between HCV and the immune response of the host. Only a limited number of studies have investigated the role of mannose-binding lectin (MBL) levels in HCV infection. The aim of the present study was to explore the relationship between MBL levels and gene polymorphisms on treatment response in patients with chronic hepatitis C (CHC). Serum MBL levels from 50 CHC patients who completed treatment at least 24 weeks before the present study and 75 healthy HCV-negative controls were measured. In addition, the presence of codon 54 mutations was investigated. Correlational analyses were performed to determine relationships between MBL levels and treatment response. In patients, mean serum MBL levels were lower and the rate of codon 54 mutations was higher. However, these differences were not statically significant. In both patients and controls, serum MBL levels were significantly lower in individuals with codon 54 mutations. Moreover, serum MBL levels and the rate of the codon 54 mutation were similar in patients regardless of treatment response. Our findings suggest that low MBL levels do not increase the susceptibility for HCV infection. Furthermore, MBL levels were not found to have a significant effect on the course of the disease or treatment response.

Subclinical infection and dosing in primary immunodeficiencies.

Subclinical infection and dosing in primary immunodeficiencies.

Extreme high prevalence of a defective mannose-binding lectin (MBL2) genotype in native South American West Andean populations.

Mannose-binding lectin (MBL) is one of the five recognition molecules in the lectin complement pathway. Common variant alleles in the promoter and structural regions of the human MBL gene (MBL2) influence the stability and serum concentration of the protein. Epidemiological studies have shown that MBL2 variant alleles are associated with susceptibility to and the course of different types of infectious and inflammatory conditions. However, it has been suggested that these alleles are maintained in different populations due to selected advantages for carriers. We investigated the MBL2 allelic variation in indigenous individuals from 12 different West Central South America localities spanning from the desert coast, high altitude Andean plates and the Amazon tropical forest within the territories of Peru (n = 249) (Departments of Loreto, Ucayali, Lambayeque, Junin, Ayacucho, Huancayo and Puno), and Ecuador (n = 182) (Region of Esmeraldas and Santo Domingo de los Colorados). The distribution of MBL2 genotypes among the populations showed that the defective variant LYPB haplotype was very common. It showed the highest frequencies in Puno (Taquile (0.80), Amantani (0.80) and Anapia (0.58) islander communities of the Lake Titicaca), but lower frequencies of 0.22 in Junin (Central Andean highland) and Ucayali (Central Amazonian forest), as well as 0.27 and 0.24 in the Congoma and Cayapa/Chachis populations in the Amazonian forest in Ecuador were also observed. Our results suggest that the high prevalence of the MBL2 LYPB variant causing low levels of functional MBL in serum may mainly reflect a random distribution due to a population bottleneck in the founder populations.

High prevalence of genetically-determined mannose binding lectin deficiency in young children with invasive pneumococcal disease

Susceptibility to invasive pneumococcal disease (IPD) correlates with age, younger children being the group with the highest burden of disease. The relevance of the innate immune response and particularly the role of mannose-binding lectin (MBL) in combating IPD is not well known. This is a 2-year prospective study (February 2011 to March 2013) including patients with IPD who attended two hospitals from Catalonia, Spain. Variables including attack rate of pneumococcal serotype (high or low invasive potential serotypes) and genotypes associated with low serum MBL levels were recorded. One hundred and forty-seven patients were included in the study. One hundred and two (69.4%) patients were children or adolescents <18 years and 45 (30.6%) were adults. Overall, low-MBL genotypes (O/O; XA/O) were detected in 23 (15.6%) patients. Children <2 years showed a higher frequency of low-MBL genotypes compared with other patients (31.0% vs. 11.9%; p = 0.031). Further sub-analysis revealed a higher proportion of low-MBL genotypes in children <2 years with IPD caused by opportunistic or low-attack-rate serotypes when compared with older patients (46.2% vs. 13.2%; p = 0.02). However, no statistically significant differences between the two groups were observed when including patients infected with invasive or high-attack-rate serotypes (18.8% vs. 10.0%; p = 0.59). Our data suggest that young children with a genetically determined low-MBL production are at a higher risk of developing IPD, particularly that caused by opportunistic or low-attack-rate pneumococcal serotypes.

Low mannose-binding lectin (MBL) levels and MBL genetic polymorphisms associated with the risk of neonatal sepsis: An updated meta-analysis

BackgroundRelatively low serum mannose-binding lectin (MBL) levels and MBL genetic polymorphisms have been implicated as high risk factors for neonatal sepsis. However, different studies have reported conflicting findings and have generally been underpowered to exclude modest effect sizes. MethodsStandard methodology of systematic reviews and meta-analyses was followed. PubMed, Embase, Cochrane, Web of Science, and Scopus databases were searched from January 1996 to December 2013. The eligible studies were collected and analyzed using Review Manager 5.2. Meta-Disc version 1.4 was used to describe and calculate sensitivity, specificity, summary receiver operator characteristic (SROC) curves and area under the curve. SROC curve analysis was used to summarize the overall performance. Funnel plots, Egger's test and Begg's test were used to investigate publication bias. ResultsSeven studies addressing low MBL levels and MBL genetic polymorphisms (structure variant A/O, A/B of Exon1) were analyzed for susceptibility to neonatal sepsis, respectively. All of these control studies were of reasonable methodological quality. The pooled unadjusted odds ratio showed that low MBL levels were significantly associated with neonatal sepsis (P=0.0002; odds ratio=4.94, 95% confidence interval=2.16–11.29) and MBL genetic polymorphisms were also significantly associated with neonatal sepsis (P=0.03; odds ratio=1.41, 95% confidence interval=1.03–1.94). In subgroup analysis based on gestational age, increased risk was found in the preterm infants in the dominant model (RR 2.33, 95%CI 1.06–5.13, P=0.03). However, no association was observed for term infants in subgroup analysis. Additionally, the SROC curve of low MBL levels in the prediction of neonatal sepsis indicated a poor predictive ability. The area under curve was 0.80 (95% confidence interval=0.74–0.86). ConclusionCurrently available evidence shows that neonates with low serum MBL levels are more than four times more likely to have neonatal sepsis compared to those with higher serum MBL levels. Neonates with MBL genetic polymorphisms are also susceptible to developing neonatal sepsis. However, a low serum MBL level was only of moderate value in detecting neonatal sepsis.

Mannose-binding lectin gene variants and infections in patients receiving autologous stem cell transplantation.

BackgroundSerious infections are common in patients undergoing autologous stem cell transplantation (ASCT) mainly because of the effects of immunosuppression. The innate immune system plays an important role in the defense against different infections. Mannose binding lectin (MBL) is a central molecule of the innate immune system. There are several promoter polymorphisms and structural variants of the MBL2 gene that encodes for this protein. These variants produce low levels of MBL and have been associated with an increased risk for infections.MethodsProspective cohort study. The incidence, severity of infections and mortality in 72 consecutive patients with hematologic diseases who underwent ASCT between February 2006 and June 2008 in a tertiary referral center were analyzed according to their MBL2 genotype. INNO-LiPA MBL2 was used for MBL2 gene amplification and genotyping. Relative risks (RR) (IC95%) as measure of association were calculated. Multivariate analysis was performed using logistic regression.ResultsA statistically significant higher number of fungal infections was found in patients with MBL2 variants causing low MBL levels (21.1%versus1.9%, p=0.016). In this MBL2 variant group infection was more frequently the cause of mortality than in the MBL2 wild-type group (p=0.05). Although not statistically significant, there was a higher incidence of major infections in the MBL2 variant group as well as a higher number of infections caused by gram-positive bacteria.ConclusionsLow-producer MBL2 genotypes were associated with an increased number of fungal infections in ASCT patients, which would suggest that MBL has a protective role against such infections. ASCT patients with MBL2 variant genotypes are more likely to die as a result of an infection.

Serum ficolin-2 in hospitalised patients with community-acquired pneumonia.

Mannose binding lectin (MBL) and ficolins contribute to host defence through activation of the lectin pathway of complement. In this study, serum levels of ficolin-2 and MBL were determined in 276 patients with community-acquired pneumonia (CAP). MBL deficiency and ficolin-2 insufficiency were defined using previously validated cut-offs. No differences were observed in MBL or ficolin-2 between patients and controls. MBL-deficient patients (<500 ng/ml) were not at higher risk of 30-day mortality odds ratio (OR) 0.97 (0.38-2.48,p=0.9) or a composite outcome of mortality, mechanical ventilation, vasopressor support (MV/VS) or complications OR 0.89 (0.44-1.77, p=0.9). Although no significant relationship between ficolin-2 insufficiency and outcome was observed, very low ficolin-2 levels (<1,200 ng/ml) were associated with an OR 1.23 (0.15-10.1), p=0.6 for 30-day mortality, 3.05 (0.61-15.2, p=0.2) for MV/VS and OR 2.05 (0.52-8.1, p=0.2) for the composite outcome. Low serum levels of MBL and ficolin-2 are not associated with CAP susceptibility. The high frequency of ficolin-2 insufficiency in patients with severe CAP would justify a larger investigation of ficolin-2 as a modifier of CAP severity.

Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus aureus Bacteremia

ObjectivesMannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients.MethodsWe conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia (≥7 days) and 46 patients with resolving bacteremia (<3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people.ResultsPatients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (P = 0.019 and P = 0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83–196.37; P = 0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19–29.57; P = 0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12–63.39; P = 0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03–4.26; P = 0.040).ConclusionsThis is the first demonstration of an association of low MBL levels and MBL2 polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB.

Mannose-Binding Lectin 2 and Ficolin-2 Gene Polymorphisms Influence the Susceptibility to Bloodstream Infections in Kidney Transplant Recipients

IntroductionBoth mannose-binding lectin (MBL) and ficolin (FCN) interact with carbohydrate structures on microbial surfaces. Polymorphisms at the promoter and exon 1 of the MBL2 gene, which are responsible for low serum levels of MBL, have been shown to play important roles to increase the risk of post-transplant infections. Three gene polymorphisms in the promoter region of FCN2 and 2 in exon 8 (+6424 G > T) are associated with serum levels of FCN2 or binding capacity toward N-acetylglucosamine on microbial surfaces. MethodsWe prospectively analyzed 81 kidney transplant recipients for 6 well-known functional single-nucleotide polymorphisms in the MBL2 and 5 in the FCN2 gene of the recipients determined by gene sequencing. The bloodstream infections collected prospectively were associated with MBL2 and FCN2 genotypic variants over the first year after kidney transplantation. ResultsMultivariate analyses only found an association of recipient QQ + PQ genotypes of MBL2 5′-UTR +4 (odds ratio [OR] = 3.677, 95% confidence intervals [CI] = 1.127–11.998, P = .031) and FCN2 exon 8 Thr 236 Met(+6359 C > T) (OR = 4.917, 95% CI = 1.229–19.667, P = .024) with the incidence of bacteremia. ConclusionRecipient QQ + PQ genotypes of MBL2 5′-UTR +4 and recipient FCN2 exon 8 Thr 236 Met(+6359 C > T) variants showed significant impacts on the risk of developing bloodstream infections after kidney transplantation.

Innate immunity in renal transplantation: The role of mannose-binding lectin

Innate immune system plays an important role in the modulation of the inflammatory response during infection and tissue injury/repair. Mannose-binding lectin (MBL) is a component of the innate immune system that activates complement via the lectin pathway. Different polymorphisms of the MBL gene are associated with MBL levels and MBL function. The relationship between MBL and disease is rather complex because MBL behaves as a double-edged sword. In the general population, low serum MBL levels are associated with higher risk of infection, type 2 diabetes, autoimmune and cardiovascular disease. However, in patients with diabetes or autoimmune disease, high MBL levels are associated with more severe renal and cardiovascular comorbidities. In renal transplantation, low MBL serum levels constitute a risk factor for infection, low grade inflammation, new onset diabetes after transplantation and subclinical rejection. Despite these associations suggest that low MBL levels should be associated with poorer renal allograft outcome, epidemiological studies evaluating the predictive value of MBL levels on graft survival are controversial. Taken together, these observations suggest that low MBL serum levels modulate chronic inflammatory response that may influence transplant outcome.

Characterization of mannose‐binding lectin (MBL) variants by allele‐specific sequencing of MBL2 and determination of serum MBL protein levels

Mannose-binding lectin (MBL) is a major component of the lectin pathway of complement activation. High and low MBL levels have been associated with susceptibility and severity of a variety of infectious and autoimmune diseases. Several single-nucleotide polymorphisms (SNPs) in the promoter region and exon 1 of the MBL2 gene are responsible for variations in serum MBL levels. We developed a sequence-based typing method for allele-specific MBL2 genotyping and measured serum MBL protein levels in 24 German blood donors. We identified the common MBL2 haplotypes including five promoter polymorphisms in linkage with the Q allele and correlated serum MBL levels with the respective genotypes. The genotyping method presented here could provide a basis for confirmatory studies in larger cohorts.

Impaired thymic function and CD4 + T lymphopenia, but not mannose-binding lectin deficiency, are risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients

Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in kidney transplant recipients (KTR), but risk factors remain poorly defined. CD4+ T lymphopenia and mannose-binding lectin (MBL) deficiency are common immunodeficiencies in KTR. Here, we investigated whether CD4+ T lymphopenia and/or MBL deficiency would be risk factors for PCP in KTR. Furthermore, the role of thymic function in CD4+ T lymphopenia and outcome was studied by assessing CD45RA+CD31+CD4+ T cell numbers (RTE, recent thymus emigrants).In 321 de novo KTR serial determinations of peripheral T lymphocyte subsets (n=281, mean 4.2 times between days 0–365) and/or MBL levels (n=112, mean 1.8 times between days 30–180) were performed. 22/321 patients developed a PCP episode on average at day 199 (107–398) post-Tx.Age correlated inversely with RTE, CD4+ and CD8+ T-cell counts until day 180 post-Tx. RTE correlated with CD4+ T-cell counts at all time-points pre- and post-Tx. PCP patients had more CMV infections (p=0.045) within the first 3months compared to controls. Importantly, PCP patients were older (p=0.008), and had lower RTE (p=0.046) pretransplant, and lower CD4+ T-cell counts pretransplant (p=0.017), at day 60 (p=0.032) and for the average of all post-Tx values (p=0.027) compared to controls. Though treatment with T-cell depleting antibodies was associated with consecutive CD4+ T lymphopenia in the whole cohort, the number of patients who received T-cell depleting antibodies was comparable between PCP and control patients (p=0.754). A multivariate stepwise logistic regression model identified only pretransplant CD4+ T-cell counts (OR 0.011, p=0.010) and acute rejection (OR 4.66, p=0.023) as predictors of PCP.In contrast, MBL levels and incidence of MBL deficiency (<500ng/ml) at days 30, 90 and 180 post-Tx were not different between PCP patients and controls.In conclusion, PCP risk was associated with higher age and related to both thymic functional impairment and long-lasting CD4+ T-lymphopenia that started already before transplantation. Despite frequent occurrences in KTR, low levels of serum MBL were not associated with increased risk for PCP. CD4+ T-cell counts and function should be addressed in prospective studies for more individualized approaches to PCP prophylaxis.

Chicken mannose-binding lectin (MBL) gene variants with influence on MBL serum concentrations

Mannose-binding lectin (MBL) plays a major role in the innate immune defence by activating the lectin complement pathway or by acting as an opsonin. Two forms of MBL have been characterised from several species, but for humans and chickens, only one form of functional MBL has been described. The human MBL2 gene is highly polymorphic, and it causes varying MBL serum levels. Several of the single-nucleotide polymorphisms (SNPs) have been associated with the severity of diseases of bacterial, viral or parasitic origin. Association between various diseases and different MBL serum levels has also been identified in chickens. In this study, two inbred chicken lines (L10L and L10H) which have been selected for low and high MBL levels in serum and four other experimental chicken lines were analysed for polymorphism in the MBL gene. The presence of polymorphisms in the MBL gene was revealed by southern blot analyses, and the differences in the serum concentrations of MBL were found to be of transcriptional origin according to real-time quantitative reverse transcription PCR analysis. Several SNPs were discovered in the promoter and the 5' untranslated region of the chicken MBL gene which resulted in the identification of six different alleles. Mapping of regulatory elements in the promoter region was performed, and SNPs that could affect the MBL serum concentration were identified. One SNP that was found to be located in a TATA box was altered in one of the six alleles only. This allele was associated with low MBL serum concentration.

Mannose-binding Lectin Genotype Influences Frequency and Duration of Infectious Complications in Children With Malignancy

Children with cancer receiving identical treatment differ in their experience of infection, suggesting that variations in immunity may influence susceptibility to infection. Studies of the influence of mannose-binding lectin (MBL), an important component of the innate immune system, in children with febrile neutropenia (FN) have yielded conflicting results. We examined the role of MBL in infection susceptibility in the largest cohort of children with cancer reported to date. MBL levels were measured and genotyping performed on children (≤16 y) receiving chemotherapy for cancer in London, UK. Clinical data from FN episodes were recorded prospectively. MBL status was assessed in 269 children; 513 episodes of FN were captured from 211 patients. Patients with MBL2 polymorphisms experienced more FN episodes than wildtype genotype (median 2 vs. 1, respectively; P = 0.074) and more episodes with documented infection (P = 0.045). Patients experiencing multiple FN episodes had lower MBL levels (P = 0.036). MBL genotype influenced duration of episode in some groups: high-risk MBL-deficient patients spent up to 5 nights longer/episode in hospital than equivalent wildtypes. These results indicate that MBL deficiency influences both susceptibility to and outcome of FN episodes and may be most important in those patients at higher risk of complications of FN.