Low Serum Mannose-binding Lectin Levels Research Articles

Erysipelothrix rhusiopathiae-specific T-cell responses after experimental infection of chickens selectively bred for high and low serum levels of mannose-binding lectin

Erysipelas, caused by infection with Erysipelothrix rhusiopathiae (ER) is an important emerging disease in laying hens. We have earlier observed prominent mannose-binding lectin (MBL) acute phase responses in experimentally ER infected chickens. The present study aimed to further examine immune responses to ER by using chickens selectively bred for high (L10H) and low (L10L) serum MBL levels. Chickens were infected with ER at 3 weeks of age and immune parameters and bacterial load were monitored in blood until day 18 after infection. Blood and spleen leukocytes collected on day 18 were stimulated in vitro with ER antigens and blast transformation of different T-cell populations was assessed. The ER infection gave a very varied outcome and no clear differences were observed between L10H and L10L chickens with respect to leukocyte counts, bacterial load or clinical outcome. Nonetheless, rapid innate responses, e.g., heterophilia and increased serum MBL levels were noted in bacteraemic chickens. All ER infected chickens also showed transient increased expression of mannose receptor MRC1L-B and decreased expression of major histocompatibility complex II on monocytes day 1 after infection indicating monocyte activation or relocation. In vitro ER stimulation showed antigen specific blast transformation of CD4+, TCRγ/δ−CD8αβ+ and TCRγ/δ+CD8αβ+ spleen cells from all infected chickens. For CD4+ and TCRγ/δ−CD8αβ+ cells the proportions of blast transformed cells were significantly higher for samples from L10L chickens than those for samples from L10H chickens. This is the first observation of ER-specific T-cells in chickens and interestingly a Th1-type response comprising cytotoxic T-cells was indicated.

High Respiratory Tract Infection Rate in Patients With Familial Mediterranean Fever.

Background Familial Mediterranean fever (FMF) is a systemic autoinflammatory disease genetically transmitted with the autosomal recessive trait. Although the pathogenesis is not certain, it is known that there is a deficiency in the regulation of the natural immune system. In this study, we aimed to search whether patients with FMF are predisposed to respiratory tract infections and whether mannose-binding lectin (MBL), as a natural immune system member, contributes to it. Methods Fifty FMF patients and 20 control groups were enrolled in the study. First, the frequencies of upper respiratory tract infection (URTI) within the previous year of both patient and control groups were evaluated retrospectively. Then, both groups were followed up for URTI for one year after starting the study. The patient's immunoglobulin A (IgA), IgM, IgG, C-reactive protein (CRP), hemogram parameters, and mannose-binding lectin were evaluated. Results The median frequency of annual URTI with a retrospective evaluation of patients was higher than that of the control group. Also, the median frequency of URTI with the prospective evaluation of patients with FMF was higher than the control group.The rate of patients with low serum IgG levels was higher in the patient group than in the control group. However, serum IgG levels of FMF patients with frequent URTI were not different from those without. The median MBL levels of both groups were similar (1312 vs. 1534 ng/mlfor the patient and control group, respectively). The rate of patients having low serum MBL levels was also similar between the groups. Conclusions In the present study, we found that patients with FMF had more URTI than healthy controls. However, the underlying cause is not fully explained. There is a need for further studies with a higher number of patients evaluating URTI in patients with FMF.

The role of Mannose-binding lectin in leprosy: A systematic review.

Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Mannose-binding lectin (MBL) is an acute phase protein associated with the pathophysiology of leprosy. Some studies have shown that there is a correlation between serum levels of MBL and polymorphisms in its gene associated with susceptibility per se and to different clinical forms. The aim of this study was to conduct a systematic review of publications in the literature that studied the association of MBL with leprosy. Databases were searched until December 2020 (PROSPERO: CRD42020158458), and additional searches were conducted scanning the reference lists of the articles. Two independent reviewers assessed the study quality using the Newcastle-Ottawa Quality Assessment Scale. Finally, 10 eligible articles were included in the study. The overall results indicated that both low MBL serum levels and polymorphisms in the structural or promoter region of its gene seem to be associated as protective factors against the development of severe forms. The results suggest that MBL may play a role in the clinical progression of leprosy.

Mannose-binding lectin serum levels and (Gly54asp) gene polymorphism in recurrent aphthous stomatitis: A case-control study.

Objectives: Dysregulation of the immune response appears to play a significant role in recurrent aphthous stomatitis (RAS) development. The main objective of this case–control study is to investigate the blood levels of mannose-binding lectin (MBL) and the frequency of the MBL2 gene (gly54asp) polymorphism in RAS patients, including 40 RAS patients and 40 healthy controls. Methods: Serum MBL levels were determined by ELISA, while the PCR-restriction fragment length polymorphism was used in MBL2 genotyping. Results: The median serum MBL level was significantly lower in the RAS group than in the control group (975 ng/mL (545–1320) vs. 1760 ng/mL (1254–2134); p≤ 0.001). The MBL levels were significantly lower in the BB genotype, whereas they were significantly higher in the wild type AA with a median of 525 and 1340 ng/mL, respectively (p =0.005). The B allele was expressed in significantly higher percentages of RAS patients than in controls. There was no significant association between MBL serum levels (p=0.685) or MBL2 codon 54 genotypes (p=0.382) with the type of ulcers. Conclusion: There was an association between low MBL serum levels and the variant allele B of the MBL2 (gly54asp) gene, and the susceptibility to RAS. As a result, potential novel therapeutic options for RAS patients with MBL deficiency should be investigated.

Serum mannose-binding lectin as a biomarker in neonatal sepsis

Objective The aim of thi s study was to evaluate the levels of mannose-binding lectin (MBL) in neonates to determine the relation between MBL deficiency and the development of sepsis. Background The MBL is a member of the collection family that is produced by the liver as an acute-phase protein. MBL activates macrophages, enhances phagocytosis, and contributes toward complement activation. Low serum MBL levels increase the risk of infections, especially if associated with other conditions such as immune deficiencies of various origins. Neonates are considered to be immunocompromised because their adaptive immunity has not yet been developed. Patients and methods This case–control study was carried out on 86 neonates classified into two groups: 45 neonates diagnosed with sepsis and 41 healthy neonates with no clinical signs or laboratory evidence of sepsis who were enrolled as a control group. Assessment of history, clinical examination, and investigations (complete blood count, C-reactive protein, blood culture, MBL levels) were performed for all neonates. Results The mean MBL serum level was found to be lower in the septic group (0.49 ± 0.1) than the control group (1.4 ± 0.3) with high statistical significance. Conclusion Low MBL serum levels are related to the development of sepsis.

Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation

There are conflicting data on the role of the lectin pathway of complement activation and its recognition molecules in acute rejection and outcome after transplantation. To help resolve this we analyzed polymorphisms and serum levels of lectin pathway components in 710 consecutive kidney transplant recipients enrolled in the nationwide Swiss Transplant Cohort Study, together with all biopsy-proven rejection episodes and 1-year graft and patient survival. Functional mannose-binding lectin (MBL) levels were determined in serum samples, and previously described MBL2, ficolin 2, and MBL-associated serine protease 2 polymorphisms were genotyped. Low MBL serum levels and deficient MBL2 diplotypes were associated with a higher incidence of acute cellular rejection during the first year, in particular in recipients of deceased-donor kidneys. This association remained significant (hazard ratio 1.75, 95% confidence interval 1.18-2.60) in a Cox regression model after adjustment for relevant covariates. In contrast, there was no significant association with rates of antibody-mediated rejection, patient death, early graft dysfunction or loss. Thus, results in a prospective multicenter contemporary cohort suggest that MBL2 polymorphisms result in low MBL serum levels and are associated with acute cellular rejection after kidney transplantation. Since MBL deficiency is a relatively frequent trait in the normal population, our findings may lead to individual risk stratification and customized immunosuppression.

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.

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.

Low serum mannose-binding lectin levels are associated with inflammation and apoptosis in early surveillance allograft biopsies

IntroductionMannose-binding lectin (MBL) is a protein of the innate immune system that participates in host defense and the tissue injury/repair process, enhancing the clearance of apoptotic cells by macrophages. The aim is to characterize the relationship between pre-transplant MBL levels, histological lesions and number of apoptotic cells in early surveillance renal allograft biopsies. Patients and methodsConsecutive renal transplant recipients were recruited and MBL levels were classified into tertiles. The first tertile was considered the low MBL group. Surveillance biopsies were done during the first 6months and were evaluated according to Banff criteria. Renal inflammatory infiltrates were studied by immunohistochemical techniques. Apoptosis was studied using morphological methods in renal tubular cells and was expressed as the number of apoptotic cells/mm2. ResultsMBL was determined in 126 patients and a surveillance biopsy with sufficient tissue was obtained in 41 of them. Patients with low pre-transplant MBL levels showed a higher acute Banff index (3.14±1.96 vs. 1.88±1.56, p=0.044) and an increased proportion of biopsies with tubular cell apoptosis The proportion of biopsies with tubular cell apoptosis was higher in patients with low pre-transplant MBL levels in comparison with patients with high MBL levels (4.3±3.6 versus 0.2±0.9 p=0.012) and increased interstitial number of inflammatory cells and significantly the macrophages/mm2 (109±118 vs. 32±46; p=0.04). ConclusionLow pre-transplant serum MBL levels are associated with more severe inflammation and increased apoptosis in early surveillance renal allograft biopsies suggesting that MBL modulates renal inflammation after transplantation

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.

MBL2polymorphisms - manifestations in Bulgarian patients with adult dermatomyositis and systemic lupus erythematosus

Deficiency in some complement factors is known to cause both systemic lupus erythematosus (SLE) and dermatomyositis (DM). Mannose-binding lectin (MBL) is a recognition molecule of the lectin pathway, and its low levels are reported to influence some autoimmune diseases. Furthermore, MBL2 polymorphisms have been described associated with low MBL serum levels due to impaired MBL structure and function. This is a pilot study to investigate the role of MBL2-550G/C (H/L), -221G/C (Y/X), Arg52Cys (D), Gly54Asp (B), Gly57Glu (C) polymorphisms and MBL serum levels as a risk factor for a development of adult DM and SLE in Bulgarian patients. None of the studied MBL2 polymorphisms appeared associated with the diseases investigated. However, we have found an increased OR of MBL2-221XY genotype in the patients with SLE (OR 1.64, 95%CI 0.77-3.52). MBL2 polymorphisms seemed to affect MBL serum levels and to be associated with the clinical features although none of the associations remained statistically significant after Bonferroni correction. The-550L allele showed an association with electromyography findings in patients with DM. The-221XY genotype was associated with photosensitivity in patients with SLE. The 54AB genotype showed an association with malar rash in patients with SLE, but it appeared decreased among SLE patients with ANA. In conclusion, our results suggest that the MBL2 polymorphisms have rather a disease modifying role and they are not associated with the disease susceptibility in adult DM and SLE among Bulgarian patients.

Low mannose-binding lectin serum levels are associated with reduced kidney graft survival

Activation of the complement system is initiated by the alternative, the classical, or the lectin pathway. As the complement system is involved in the pathophysiology of graft rejection after kidney transplantation, we investigated the possible role of mannose-binding lectin in kidney transplantation and the influence of human leukocyte antigen (HLA) immunization on this process. In a prospective study of 544 kidney transplant patients over a follow-up period of 5 years, low serum levels of this lectin at the time of transplantation were found to be significantly associated with decreased 5-year death-censored graft survival (hazard ratio 1.68). Subanalysis showed that this association was confined to non-HLA-immunized patients (hazard ratio 1.93). The strongest association was seen in non-HLA-immunized patients receiving a kidney from a deceased donor (hazard ratio 2.93). No significant association with mannose-binding lectin levels and graft survival were found in HLA-immunized patients. Variant MBL2 genotypes causing low mannose-binding lectin serum concentrations showed the same association pattern. Our findings demonstrate a clear protective role of mannose-binding lectin and thus innate immunity in maintaining kidney graft survival, but these are probably overruled by HLA immunization.

Genetic polymorphisms and serum levels of mannose-binding lectin in Chinese pediatric patients with common infectious diseases

Mannose-binding lectin (MBL) is a collagen-like serum protein that plays an important role in first-line host defense, especially in infants and young children. The objective of this study was to explore the genetic polymorphisms and serum protein levels of MBL in Chinese pediatric patients with common infectious diseases, including recurrent respiratory infection (RRI), acute respiratory infection (ARI), active cytomegalovirus (CMV) infection, localized abscess, and otitis media. MBL genetic polymorphisms of 151 pediatric patients with infectious diseases and 105 healthy controls were detected by PCR and sequencing. Serum MBL levels of all the patients and controls were measured using a Human MBL ELISA Kit. Differences in MBL genetic polymorphisms and serum levels between patients and controls were analyzed by statistical methods. The frequencies of allele H/L at position -550 of the promoter and three haplotypes - HYPA, HYPB, and LYPB - were statistically different between patients and controls (p<0.05). The frequencies of genotypes 'YA' and 'XB', relevant to serum protein levels, were also significantly different between patients and controls (p<0.05). Serum MBL levels of patients with active CMV infection were significantly lower than those of controls (p<0.05). Conversely, serum MBL levels of patients with ARI and localized abscess were significantly higher than those of controls (p<0.05). Genetic polymorphisms attributable to mutations in the promoter and exon 1 of the MBL2 gene appear to be relatively common in pediatric patients with infectious diseases. Low serum MBL levels may play a role in the high sensitivity of pediatric CMV infections.

Serum Levels of Mannose-Binding Lectin and the Risk of Infection in Pediatric Oncology Patients With Chemotherapy

Morbidity and mortality due to infections remain serious problems in pediatric oncology patients receiving chemotherapy. Association of mannose-binding lectin (MBL) levels with an increased risk for infection in previous studies was contradictory. The aim of this study was to determine whether MBL deficiency is associated with the risk of infections in pediatric oncology patients. Before the start of chemotherapy a blood sample was taken from 75 patients with acute lymphoblastic leukemia and MBL serum concentration was measured using a commercially enzyme-linked immunosorbent assay kit. Twenty patients had concentrations under 1000 µg/L, defining MBL deficiency and the remaining 55 patients had concentrations >1000 µg/L. Ten patients suffered from more than 1 episode of severe infection. Sixty-five percent of patients with MBL below 1000 µg/mL suffered from 2 or more episodes of infections (3 of 16 individuals with 1 severe infection; 10 of 16 with 2 and 3 of 16 with 3), in contrast to only 29 of 55 (52%) patients with MBL above 1000 µg/mL (19 of 27 individuals with 1 severe infection and 10 of 27 with 2). The difference between 2 groups was significant (P<0.001). The results of this study indicate that low MBL serum levels (<1000 µg/L) identify pediatric cancer patients at increased risk for infections.

Serum Concentration of Complement Components of the Lectin Pathway in Maintenance Hemodialysis Patients, and Relatively Higher Levels of L‐Ficolin and MASP‐2 in Mannose‐Binding Lectin Deficiency

Mannose-binding lectin (MBL), L-ficolin and MBL associated serine protease-2 (MASP-2) are molecules involved in initiation of the lectin pathway (LP) in the complement system. Although MBL deficiency is observed in almost 10% of healthy people, studies of associations between MBL deficiency and end-stage renal disease (ESRD) remain rare. The objective of the present study is to clarify the significance of the LP in maintenance hemodialysis (HD) patients, especially in terms of MBL levels. Two hundred and forty-four HD patients who had been followed up for 74±84months and 199 healthy controls were included in this study. Measurements of serum concentrations of MBL, L-ficolin, and MASP-2 were performed. Low serum MBL levels (<0.1µg/mL) in the patients were confirmed by examination of a point mutation in the Mbl-2 gene. Seventeen HD patients (7%) and 20 healthy controls (10%) had MBL deficiency. During the follow-up period, 99 patients died. There was no significant difference in the frequency of deaths by infectious diseases between MBL deficient and non-deficient patients. In both patients and healthy controls with MBL deficiency, the serum concentration of L-ficolin tended to be high, and that of MASP-2 was significantly high (P<0.05). MBL deficiency is not a risk factor for HD induction or life-threatening infections. It is postulated that the elevation of concentration of the two components of the LP, L-ficolin and MASP-2, may compensate for the insufficient activity of the LP in MBL deficiency.

High Levels of Mannose-Binding Lectin Are Associated With Poor Outcomes After Lung Transplantation

Mannose-binding lectin (MBL) is a key molecule of the innate immune system and, in addition to the classical and alternative pathways, a principle driver of complement activation. Genetic mutations of MBL are common, result in low serum levels of MBL, and are associated with increased infection risk in solid-organ transplant recipients. We performed a retrospective study of MBL2 genotype and plasma and bronchoalveolar lavage (BAL) MBL levels in 37 lung transplant recipients (LTR). Plasma MBL levels were measured pretransplant and both plasma and BAL MBL levels were measured at 3, 6, and 12 months after lung transplantation. MBL2 genotyping was performed on recipient and donor peripheral blood mononuclear cells. Clinical variables analyzed included primary graft dysfunction, intensive care unit stay, acute allograft rejection, infection, bronchiolitis obliterans syndrome (BOS), and mortality. Plasma MBL levels posttransplant were predicted by recipient, and not donor MBL2 genotype. Compared with pretransplant levels, plasma MBL was significantly increased at 3, 6, and 12 months posttransplant (P<0.05). LTR who developed BOS or died during the study period had higher plasma MBL levels at 6 and 12 months posttransplant (P ≤ 0.05) compared with LTR with stable graft function. MBL was not routinely detected in the lung allograft; however if present in the BAL at 3 and 6 months posttransplant, it was associated with the later development of BOS (P<0.05). Plasma MBL levels increase after lung transplantation and persistently increased MBL levels are associated with poor long-term outcomes.