Serum Mannose-binding Lectin Levels Research Articles

Mannose-binding lectin and mannose-binding lectin–associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults

Community-acquired pneumonia (CAP) is the leading cause of death from infection in developed countries. Mannose-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) deficiencies are common primary immunodeficiencies the clinical penetrance of which remains controversial. MBL is a serum lectin that mediates phagocytosis and activates the lectin pathway of complement involving MASP-2. We sought to evaluate the significance of MBL deficiency (O/O genotypes) and insufficiency (O/O plus XA/O genotypes), as well as MASP-2 deficiency (D105G mutation), in the susceptibility to and severity and outcome of CAP in adults. MBL and MASP-2 serum levels, as well as lectin pathway activity with regard to MBL2 and MASP2 genotypes, were measured in healthy control subjects. For susceptibility, 848 patients with CAP, 1447 healthy control subjects, and a control group of 519 patients without relevant infectious diseases were studied in a case-control study. Severity and outcome were evaluated in a prospective study of the 848 patients. We found similar frequencies of MBL2 and MASP2 alleles and genotypes among patients and control subjects. However, in a multivariate analysis MBL insufficiency was associated with the development of the most severe forms of sepsis (P = .007), acute respiratory failure (P = .009), multiorgan dysfunction syndrome (P = .036), intensive care unit admission (P = .020), and death (P = .003). Our large study suggests that MBL plays a redundant role in human defenses against primary infection, at least in adults with CAP, and provides, for the first time, evidence that MBL insufficiency predisposes to higher severity and fatal outcome in patients with CAP, irrespective of the causal microorganisms.

The Role of Mannose-Binding Lectin in Susceptibility to Infection in Preterm Neonates

Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the impact of MBL on susceptibility and severity of infection in preterm neonates during their first month of life. One hundred fifty eight preterm neonates were genotyped for MBL mutations by heteroduplex analyses. Consecutive serum MBL levels were measured by ELISA and clinical and laboratory data, including blood cultures, were collected for each baby. A third of the premature neonates had genetically determined MBL deficiency. In addition, MBL levels were also low in the first week of life and lower in neonates with a wild type genotype who were less than 28 wk gestation or a birth weight of less than 1000 g, thereby increasing the number of neonates with a low MBL level at birth. MBL deficiency was associated with an increased risk of sepsis (p < 0.01). This study indicates that MBL levels are low in neonates at birth and renders premature neonates to an increased risk of infection.

Mannose‐binding lectin gene polymorphisms and the development of coal workers' pneumoconiosis in Japan

Infection, immunity and genetic factors play roles in the development of coal worker's pneumoconiosis (CWP) and progressive massive fibrosis (PMF). We investigate whether the genetic polymorphisms of mannose-binding lectin (MBL), one of the key molecules of innate immunity, is associated with the susceptibility to CWP. MBL2 polymorphisms (codon54, promoter -221, and -550) were assessed for 197 patients with CWP (119 with nodular CWP and 78 with PMF) and 153 unexposed regional controls. Serum MBL concentrations were measured in 119 CWP patients. Three polymorphisms were in linkage disequilibrium for all study populations. The MBL2 genotype and haplotypes were associated with lower serum MBL levels. The frequency of such MBL2 genotype and haplotypes were significantly higher in patients with CWP compared to controls, whereas these distributions were not different between patients with nodular CWP and those with PMF. MBL2 polymorphisms and haplotypes may be one of the genetic determinants for the susceptibility of CWP.

Association of Mannose-Binding Lectin Gene Polymorphism but Not of Mannose-Binding Serine Protease 2 with Chronic Severe Aortic Regurgitation of Rheumatic Etiology

N-Acetylglucosamine (GlcNAc) is the major immunoepitope of group A streptococcal cell wall carbohydrates. Antistreptococcal antibodies cross-reactive with anti-GlcNAc and laminin are present in sera of patients with rheumatic fever. The cross-reactivity of these antibodies with human heart valvular endothelium and the underlying basement membrane has been suggested to be a possible cause of immune-mediated valve lesion. Mannose-binding lectin (MBL) encoded by the MBL2 gene, a soluble pathogen recognition receptor, has high affinity for GlcNAc. We postulated that mutations in exon 1 of the MBL2 gene associated with a deficient serum level of MBL may contribute to chronic severe aortic regurgitation (AR) of rheumatic etiology. We studied 90 patients with severe chronic AR of rheumatic etiology and 281 healthy controls (HC) for the variants of the MBL2 gene at codons 52, 54, and 57 by using a PCR-restriction fragment length polymorphism-based method. We observed a significant difference in the prevalence of defective MBL2 alleles between patients with chronic severe AR and HC. Sixteen percent of patients with chronic severe AR were homozygotes or compound heterozygotes for defective MBL alleles in contrast to 5% for HC (P = 0.0022; odds ratio, 3.5 [95% confidence interval, 1.6 to 7.7]). No association was detected with the variant of the MASP2 gene. Our study suggests that MBL deficiency may contribute to the development of chronic severe AR of rheumatic etiology.

ORIGINAL ARTICLE: MBL2 Genetic Screening in Patients with Recurrent Vaginal Infections

Problem Mannose‐binding lectin (MBL) is an important component of the innate immunity, present at the mucosal level in vagina: a common pathogen’s entry point.Method of study We used a rapid genotyping method based on melting temperature assay to search for three single nucleotide polymorphisms (SNPs) located in the first exon of the MBL2 gene and we also measured MBL serum levels in patients with recurrent bacterial vaginosis (rBV) and recurrent vulvovaginal candidiasis (rVVC).Results Detected frequencies of MBL2 SNPs were comparable to the ones already reported for the Italian population and no significant differences were found between rVVC, rBV and controls. MBL serum levels did not show significant differences between the studied groups.Conclusion No correlation for the screened mutations has been found neither in protecting nor in favoring the infection in rVVC and rBV patients. Our data demonstrate a lack of association between functional polymorphisms in the first exon of MBL2 gene, MBL deficiency,VVC and rBV.

Mannose-binding lectin (MBL) genotype in relation to risk of nosocomial infection in pre-term neonates in the neonatal intensive care unit

Mannose-binding lectin (MBL) plays an important role in the innate immune response. Three alleles in the MBL gene, and one allele of the promoter, independently cause low serum MBL levels as compared with the wild-type. This study investigated the relationship between MBL genotype and the occurrence of nosocomial infection among neonates in a neonatal intensive care unit (NICU). Prospectively gathered information concerning nosocomial infection was available for 742 neonates from a recently performed surveillance study in an NICU. DNA was isolated from Guthriecards for a subgroup of 204 neonates who stayed in the NICU for > or =4 days. After a pre-PCR for the MBL gene in blood spots on Guthriecards, mutations were analysed by real-time PCR to detect six mutations in the MBL gene. An MBL genotype could be determined for 186 neonates. As compared to term neonates, genotypes encoding MBL-deficient haplotypes were significantly more prevalent among pre-term neonates. Forty-one of these neonates developed sepsis, with blood cultures yielding coagulase-negative staphylococci in 25 cases. Pneumonia occurred in 30 cases, with various causative organisms. No relationship was found between MBL genotype and the risk of nosocomial sepsis or pneumonia, even after correction for birth-weight, perhaps because of an insufficient correlation between genotype and the concentration of functional MBL. In addition, most bloodstream infections in the NICU were caused by coagulase-negative staphylococci, to which MBL binds poorly.

Infectious Complications After Simultaneous Pancreas-Kidney Transplantation: A Role for the Lectin Pathway of Complement Activation

Mannose-binding lectin (MBL) is a recognition molecule of the lectin pathway of complement activation, and its serum levels are largely determined by frequently occurring polymorphisms of the MBL gene. We questioned whether MBL deficiency influences infectious complications in patients after simultaneous pancreas-kidney transplantation (SPKT). Infectious complications in the first year after transplantation were scored retrospectively in 152 consecutive SPKT patients who received their transplant at our center between 1990 and 2005. Pretransplant serum MBL levels were determined with enzyme-linked immunosorbent assay. Every 500 ng/mL increase in baseline MBL was associated with an odds ratio of 0.83 (P=0.045) for urinary tract infections and an odds ratio of 0.68 (P=0.029) for urosepsis. Urosepsis was significantly more common in patients with low baseline MBL (<400 ng/mL) compared with those with greater MBL levels (22.7% vs. 8.3%, P=0.015). No significant influence of MBL on the occurrence of wound infections and cytomegalovirus disease could be demonstrated. With the current study, we show that high levels of serum MBL are associated with protection against urinary tract infections and, more specifically, against urosepsis after SPKT. These data indicate an important role for the lectin pathway of complement activation in antimicrobial defense in these transplant recipients.

Mannose‐binding lectin is involved in multiple organ dysfunction syndrome after cardiac surgery: effects of blood transfusions

Serum levels of mannose-binding lectin (MBL), a recognition molecule of the lectin pathway of complement, are highly variable, based on genetic variation. After cardiac surgery, extracorporeal circulation and ischemia-reperfusion injury initiate a systemic inflammatory response, which can evolve to multiple organ dysfunction syndrome (MODS). Preoperative transfusions of allogeneic white blood cells (WBCs) contribute to infectious and inflammatory complications. This study investigates the role of MBL in relation to blood transfusions and complications after cardiac surgery. In cardiac surgery patients who participated in a randomized trial comparing leukoreduced with buffy coat-depleted red blood cell (RBC) transfusions, circulating MBL was measured pre- and postoperatively by enzyme-linked immunosorbent assay (ELISA). Data were related to the incidence of complications and to the transfusions the patients received. Patients with high preoperative serum MBL levels (>400 ng/mL) show a significant (52 +/- 12%) decrease of serum MBL postoperatively, whereas patients with low serum MBL levels (< or =400 ng/mL) show a significant increase of serum MBL levels after surgery (140 +/- 106%), which was further enhanced by fresh-frozen plasma (FFP) transfusions. MBL levels were not associated with infections, sepsis, or death. Patients with MBL deficiency (MBL < or = 80 ng/mL) were protected against development of MODS (p = 0.016), whereas FFP transfusion abolished this protection (p = 0.048). Cardiac surgery is associated with MBL consumption, independent of the transfusion of allogeneic WBCs. Patients with MBL deficiency develop no MODS, unless they have been transfused with FFP, which is associated with MBL reconstitution. Therefore, sustained MBL deficiency may be a favorable status for patients undergoing cardiac surgery.

RESEARCH OF MANNOSE-BINDING LECTIN AND INTERLEUKINS 10, 12, AND 18 IN CHILDREN WITH HENOCH-SCHÖNLEIN PURPURA

INTRODUCTION: Henoch-Schönlein Purpura (HSP) is a common vasculitis in children, and the unbalance of T-helper 1/T-helper 2 plays an important part in its pathogenesis. Mannose-binding lectin (MBL) is an important component of innate immunity and related with a lot of diseases with immunologic derangement. However, we do not know the relationship between MBL and HSP. OBJECTIVE: We aimed to explore the serum level and gene polymorphisms of MBL and the levels of interleukin 10 (IL-10), IL-12, and IL-18 in supernatant of peripheral blood mononuclear cells of children with HSP and HSP nephritis (HSPN) and of healthy children. METHODS: The concentrations of MBL and IL-10, IL-12, and IL-18 were measured by enzyme-linked immunosorbent assay: MBL gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction with sequence-specific primers. RESULTS: The serum MBL levels in the 23 children with HSP were not significantly different from 27 children with HSPN (P = .95) or 18 normal children. The levels of IL-18 in the supernatant of peripheral blood mononuclear cells in the 3 groups were not significantly different from each other (P = .47, .15, and .14). The levels of IL-10 in children with HSP and HSPN were not different from each other (P = .70), but both were significantly different from those in the normal children (P = .04 and .01). The levels of IL-12 in children with HSP were different from those in the children with HSPN (P = .04). The MBL promoter genotype and the frequency of alleles were not different between the children with HSP and HSPN or between those 2 groups compared with the normal group. CONCLUSIONS: IL-12 probably plays an important role in the renal involvement in HSP. The position of MBL in the pathogenesis of HSP and HSPN remains to be confirmed.

MANNOSE-BINDING LECTIN (MBL) GENE POLYMORPHISMS AND SERUM MBL LEVELS IN CHILDREN WITH RECURRENT RESPIRATORY TRACT INFECTION

INTRODUCTION: Mannose-binding lectin (MBL) is a plasma collectin and is considered an important component of innate immunity. Its plasma concentration is, for the most, part genetically determined by a series of single nucleotide polymorphisms located both in the structural gene and in the promoter region. MBL deficiency may be associated with increased susceptibility to infectious disease and autoimmune disorders. OBJECTIVE: Our goal was to establish the reference serum level of MBL in children, investigate the correlation between MBL gene polymorphisms and its serum level in Chinese Han nationality, and MBL gene polymorphisms and serum level in children with recurrent respiratory tract infections. METHODS: The concentrations of oligomerized MBL in plasma were measured by enzyme-linked immunosorbent assay, and MBL gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction with sequence-specific primers. RESULTS: The median MBL level in 470 normal children was 2536 ng/mL (range: 0–7860 ng/mL), and P2.5 to P97.5 was 161 to 5070 ng/mL. Two promoter polymorphisms, -550 and -221, and coding variants at codon 54 of the MBL gene affected the protein level significantly, and the most frequent genotype in Hans was HYPA/HYPA. Serum MBL levels were significantly lower in patients with recurrent respiratory tract infections (RRTIs) compared with healthy controls (H = 6.661; P &amp;lt; .05), and the frequency of the promoter LXP haplotype was significantly higher in patients with RRTIs than in controls (χ2 = 4.71; P = .03). The prevalence of the B allele in patients with RRTIs was higher than that in controls, but the difference did not reach significance (χ2 = 0.18; P &amp;gt; .05). CONCLUSIONS: The MBL reference value in China is 161 ng/mL. Children with MBL concentrations of &amp;lt;161 ng/mL, therefore, were deemed to be MBL deficient, and LXP is a risk factor for recurrent respiratory tract infections in this population.

Polymorphism in the promoter region of the mannose-binding lectin gene among human T-cell lymphotropic virus infected subjects

The present study investigated the frequency of the mutations at positions -550 and -221 of the mannose-binding lectin (MBL) gene in a sample of 75 human T-cell lymphotropic virus (HTLV) infected patients and 96 HTLV seronegative controls, in order to evaluate the occurrence of a possible association between the polymorphism and HTLV infection. A sequence specific primer-polymerase chain reaction was used for discrimination of the polymorphism. The analysis of allele frequencies at position -550 did not show any significant differences between HTLV infected group and controls, but there was a significant difference at position -221. The comparative analysis of haplotypes frequencies were not significant, but the genotype frequencies between the two groups, revealed a higher prevalence of genotype LYLX (25.3%), associated with medium and low MBL serum levels among HTLV infected subjects. The odds ratio estimation demonstrated that the presence of genotype LYLX was associated with an increased risk of HTLV infection (p = 0.0096; 1.38 < or = IC95% < or = 7.7605). There was no association between proviral load and the promoter polymorphism, but when promoter and exon 1 mutations were matched, it was possible to identify a significant higher proviral load among HTLV infected individuals carrying haplotypes correlated to low serum levels of MBL. The present study shows that the polymorphism in the promoter region of the MBL gene may be a genetic marker associated with HTLV infection, and emphasizes the need for further studies to determinate if the present polymorphism have any impact on diseases linked to HTLV infection.

MBL2 variants in relation to common childhood infections and atopy‐related phenotypes in a large German birth cohort

Mannose-binding lectin (MBL) is considered an important component of innate immunity. Four functional MBL2 alterations in codons 52, 54, 57 and in the promoter at position c.1-290 are correlated with significantly lowered MBL serum levels. These variants have been associated with susceptibility to a variety of infectious agents as well as with various immunologic disorders including asthma. To reassess these observations, we analysed the four above mentioned MBL2 variants in 749 children, who were recruited by the German Multicenter Allergy Study and were prospectively evaluated for common respiratory childhood infections and atopy-related phenotypes from birth up to the age of 11 yr. We performed genotyping by melting curve analysis using fluorescence resonance energy transfer probes and the LightCycler. In contrast to previous studies, we found an association of MBL2 variants neither with the frequency of common respiratory childhood infections at any age nor with asthma or other atopy-related phenotypes. Our data suggest that MBL deficiency does not represent a pre-disposing factor for respiratory infections or atopic disorders in infants and children.

Serum Mannose-Binding Lectin Levels are Linked with Respiratory Syncytial Virus (RSV) Disease

The innate immune response facilitates the quality of the adaptive immune response and is critical to an individual's susceptibility to infection and disease. Mannose-binding lectin (MBL) is a plasma protein with anti-microbial properties that binds a wide range of pathogens to flag them for immune destruction independent of antibodies. In this study, serum MBL levels were measured in 81 children <5 years old experiencing acute respiratory syncytial virus infection and in 40 control children to determine the association with disease severity. Almost 70% of all RSV-infected children had low to intermediate MBL levels (<500 ng/ml) compared to controls, and most of the <6 months old RSV interned patients had low to intermediate levels. No differences were detected in MBL levels between case and control children <1 month old. Analysis of the T-cell compartment in peripheral blood mononuclear cells (PBMC) from acute RSV-infected and control children showed that the percent CD4+ T cells was statistically lower in RSV-infected children > or =6 months old compared to controls, while the percent CD8+ T cells in RSV-infected and control PBMC was generally similar. These results suggest that low serum MBL levels may be a marker of RSV disease severity in children and that MBL may be important in limiting RSV disease pathogenesis.

Lung Cancer Survival and Functional Polymorphisms in MBL2, an Innate-Immunity Gene

The relationship among chronic inflammation, innate immunity, and cancer is well established. Mannose-binding lectin (MBL) is a key player in innate immunity. Five polymorphisms in the promoter and first exon of the MBL2 gene alter the expression and function of MBL in humans and are associated with inflammation-related disease susceptibility. These five polymorphisms create six well-characterized haplotypes that result in lower (i.e., LYB, LYC, HYD, and LXA) or higher (i.e., HYA and LYA) serum MBL concentrations. We investigated whether survival of patients with lung cancer was associated with these polymorphisms. We used a multivariable Cox proportional hazards model to study the association between MBL2 polymorphisms and their haplotypes and diplotypes in 558 white and 173 African American patients with non-small-cell lung cancer in the Baltimore, MD, area and lung cancer mortality. Smoking history and race were obtained from interviews, tumor stage was obtained from medical records, and cause of death was obtained from the National Death Index. All statistical tests were two-sided. We found a statistically significant association between the X allele of the promoter Y/X polymorphism (which results in a lower serum MBL concentration) and improved lung cancer survival among white patients (risk ratio [RR] of death from lung cancer with X/X or X/Y genotype compared with Y/Y genotype = 0.61, 95% confidence interval [CI] = 0.46 to 0.81) but not among African American patients (RR = 1.11, 95% CI = 0.69 to 1.77). The associations among white patients were strongest in heavy smokers and were independent of stage. We also found a statistically significant interaction between the Y/X polymorphism and race for lung cancer survival (P(interaction) = .019). The MBL2 LXA haplotype and XA/B diplotype, which are also associated with low serum MBL levels, were statistically significantly associated with improved lung cancer survival among white patients. The functional Y/X polymorphism of the innate-immunity gene MBL2 and MBL2 haplotypes and diplotypes appear to be associated with lung cancer survival among white patients.

The MBL2 ‘LYQA Secretor’ Haplotype Is an Independent Predictor of Postoperative Myocardial Infarction in Whites Undergoing Coronary Artery Bypass Graft Surgery

Mannose-binding lectin (MBL) is an important component of innate immunity and activator of the lectin complement pathway. Within the MBL2 gene are seven 5' "secretor" haplotypes that code for altered serum MBL levels and complement activation. However, recent evidence suggests that 3' MBL2 haplotypes may also modify MBL function and circulating levels. Because MBL and the lectin complement pathway have been implicated in cardiovascular injury, we investigated whether MBL2 haplotypes are independently associated with an increased risk of postoperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery. Genotyping of 18 polymorphic sites within the MBL2 gene was performed in a prospective, longitudinal multi-institutional study of 978 patients undergoing primary coronary artery bypass graft-only surgery with cardiopulmonary bypass between August 2001 and May 2005. After adjustment for multiple comparisons by permutation testing, multivariate, stepwise logistic regression, including a score test, was performed controlling for patient demographics, preoperative risk factors, medications, and intraoperative variables to determine if MBL2 secretor haplotypes are independent predictors of PMI in whites undergoing primary coronary artery bypass graft surgery. Neither the 5' nor 3' MBL2 haplotypes alone were associated with an increased incidence of PMI. However, the incidence of PMI in whites (n=843) expressing the combined MBL2 5' LYQA secretor haplotype (CGTCGG) and 3' haplotype (CGGGT) was significantly higher than in whites not expressing the haplotype (38% versus 10%; P<0.007). Moreover, the combined MBL2 LYQA secretor haplotype was an independent predictor of PMI in whites after primary coronary artery bypass graft surgery after adjustment for other covariates (P<0.02; adjusted OR: 3.97; 95% CI: 1.30 to 12.07). The combined MBL2 LYQA secretor haplotype in whites was also an independent predictor of postoperative CKMB levels exceeding 60 ng/mL (P<0.02; adjusted OR: 4.48; 95% CI: 1.95 to 16.80). Inclusion of the combined MBL2 LYQA secretor haplotype improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.715 versus 0.705). The combined MBL2 LYQA secretor haplotype is a novel independent predictor of PMI and may aid in preoperative risk stratification of whites undergoing primary coronary artery bypass graft surgery.

English

&nbsp; One of the important immunological factors in diseases is mannose binding lectin(MBL).&nbsp;The aim of present study is to determine the distribution of the alleles of mannose-binding lectin gene codon 52, 54, 57 and promoter variants H/L, X/Y, P and Q in confirmed VL patients as an intracellular pathogen while compares with extracellular pathogens (in renal infection) and seek correlation between these variants and intracellular and extracellular infections. Fifty eight confirmed VL patients&rsquo; blood samples were compared with fifty eight blood samples of patients received renal in results of renal infections. MBL genotypes were investigated by polymerase chain reaction and restriction fragment length polymorphism.&nbsp;Frequency of defective allele B in extracellular pathogens was more than intracellular pathogens (P = 0.0001), and in contrary prevalence of wild type allele A in intracellular pathogens was more than extracellular pathogens (P = 0.0001), and in&nbsp;other alleles and variants there was not any significant difference. In conclusion, there was more prevalence of alleles with low mannose binding lectin serum level in extrallelular pathogens which can be consider as a risk factor for these infections. In other hand prevalence of high concentration alleles in intracellular pathogens indicate the role of mannose binding lectin level for susceptibility to intracellular pathogens.&nbsp; &nbsp; Key words:&nbsp;Extracellular, genotype, infection, intracellular, mannose binding lectin, pathogen.

Genetically determined high serum levels of mannose-binding lectin are associated with ischemic heart disease in rheumatoid arthritis—Mainly in conjunction with agalactosyl IgG

Genetically determined high serum levels of mannose-binding lectin are associated with ischemic heart disease in rheumatoid arthritis—Mainly in conjunction with agalactosyl IgG

Human serum mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1): determination of levels in body fluids and identification of two forms in serum.

We developed an ELISA for human serum MASP-1, a C1s-like serine protease which is known to function in C4 and C2 activation. We then determined MASP-1 levels in 1063 sera from normal Japanese subjects ranging in age from 3 to 100 years, as well as in certain body fluids using this assay. Individual serum MASP-1 levels ranged from 1.48 to 12.83 microg/ml, with a normal frequency distribution pattern. The arithmetic mean +/- s.d. of MASP-1 levels in serum was 6.27 +/- 1.85 microg/ml, whereas levels of MASP-1 in cerebrospinal fluid and in urine were almost undetectable. When the mean +/- s.d. of serum MASP-1 was calculated for each age group (10 year range) and values were then compared, the age group consisting of 3-9-year-olds (7.54 +/- 1.39 microg/ml) was found to have the highest value. When MASP-1 was measured in cord blood, it was shown that levels were already as high as those of 3-9-year-olds. The serum MASP-1 level was found to be as strongly dependent on age as is the serum MBL level. MASP-1 and MBL are thought to play an active part in immunity in younger people. It was found that the serum level of MASP-1 was much higher than that of MBL, and the major portion of human serum MASP-1 appeared to exist in the circulation as a form unbound to MBL.

Low Pretransplantation Mannose-Binding Lectin Levels Predict Superior Patient and Graft Survival after Simultaneous Pancreas-Kidney Transplantation

Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and renal failure. However, this procedure is characterized by a high rate of postoperative infections, acute rejection episodes, and cardiovascular mortality. The lectin pathway of complement activation contributes to cardiovascular disease in diabetes and may play an important role in inflammatory damage after organ transplantation. This study therefore sought to determine how mannose-binding lectin (MBL), a major recognition molecule of the lectin pathway of complement activation, influences outcome after SPKT. MBL serum levels were determined in 99 and MBL genotypes in 97 consecutive patients who received an SPKT from 1990 through 2000 and related to patient and graft survival. At 12 yr, cumulative death-censored kidney graft survival was 87.5% in patients with an MBL level <400 ng/ml and 74.8% in the group with MBL levels >400 ng/ml (P = 0.021). Pancreas graft survival was significantly better in patients with low MBL levels (P = 0.016). MBL levels >400 ng/ml were associated with a hazard ratio of 6.28 for patient death (95% confidence interval 1.8 to 20.3; P = 0.003). Accordingly, survival was significantly better in recipients with MBL gene polymorphisms associated with low MBL levels. These findings identify MBL as a potential risk factor for graft and patient survival in SPKT. It is hypothesized that MBL contributes to the pathogenesis of inflammation-induced vascular damage both in the transplanted organs and in the recipient's native blood vessels.

Mannose binding lectin gene polymorphisms and asthma

Bronchial asthma is a chronic inflammatory disorder of the airways. Recently, it has been suggested that complement plays significant roles in asthma. Mannose-binding lectin (MBL) is one of the key molecules in complement activation pathways that are associated with several infectious and immune disorders. To investigate whether MBL plays roles in asthma, we analysed MBL2 polymorphisms (allele B, H/L and Y/X) and plasma MBL levels in a Japanese adult population including 232 healthy controls and 579 asthmatics. Although there was linkage disequilibrium among the three polymorphisms, each polymorphism significantly affects serum MBL levels independently. However, there were no significant differences between asthmatics and controls in MBL2 genotype distribution and in MBL concentrations [1.47+/-0.07(SE) mg/L for asthmatics and 1.66+/-0.14 mg/L for controls, P=0.2]. MBL levels and genotype have no significant relationship with serum IgE, pulmonary functions, and the severity of asthma. Although plasma MBL levels depend on the MBL2 polymorphisms, these polymorphisms and plasma MBL levels are not associated with the asthma phenotype.