Mannose-binding Lectin Deficiency Research Articles

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.

Deficiency of mannose-binding lectin is a risk of Pneumocystis jirovecii pneumonia in a natural history cohort of people living with HIV/AIDS in Northern Thailand.

Mannose-binding lectin (MBL) plays a pivotal role in innate immunity; however, its impact on susceptibility to opportunistic infections (OIs) has not yet been examined in a natural history cohort of people living with HIV/AIDS. We used archived samples to analyze the association between MBL expression types and risk of major OIs including Pneumocystis jirovecii pneumonia (PCP), cryptococcosis, talaromycosis, toxoplasmosis, and tuberculosis in a prospective cohort in Northern Thailand conducted from 1 July 2000 to 15 October 2002 before the national antiretroviral treatment programme was launched. Of 632 patients, PCP was diagnosed in 96 (15.2%) patients, including 45 patients with new episodes during the follow-up period (1006.5 person-years). The total history of PCP was significantly associated with low MBL expression type: high/intermediate (81/587, 13.8%), low (10/33, 30.3%) and deficient (5/12, 41.7%) (p = 0.001), whereas the history of other OIs showed no relation with any MBL expression type. Kaplan-Meier analysis (n = 569; log-rank p = 0.011) and Cox's proportional hazards model revealed that deficient genotype dramatically increased the risk of PCP, which is independent upon sex, age, CD4 count, HIV-1 viral load and hepatitis B and C status (adjusted hazard ratio 7.93, 95% confidence interval 2.19-28.67, p = 0.002). Deficiency of MBL expression is a strong risk factor determining the incidence of PCP but not other major OIs.

РЕЦИДИВИРУЮЩАЯ СТРЕПТОКОККОВАЯ ИНФЕКЦИЯ У РЕБЕНКА С ВРОЖДЕННЫМ ДЕФИЦИТОМ МАННОЗОСВЯЗЫВАЮЩЕГО ЛЕКТИНА

Objective of the research: to present the clinical and laboratory features of a child with a congenital deficiency of mannose-binding lectin (MBL). Materials and methods: DNA samples of 112 children suffering from frequent infectious diseases were analyzed by high-throughput sequencing (Illumina) using a panel including 338 genes associated with the development of primary immunodeficiencies. A search for pathogenic alleles of MBL2 was performed. A homozygous mutation in the MBL2 gene was detected in one of 112 examined patients, heterozygous carriage of the pathogenic MBL2 allele in two children. The story of a child with a homozygous defect of this gene is presented. The role of MSL deficiency in the development of a recurrent course of a nasopharyngeal infection caused by group A streptococcus, the formation of a chronic disease of the tonsils and adenoids is demonstrated.

Levels of mannose-binding lectin (MBL) associates with sepsis-related in-hospital mortality in women

BackgroundMannose-binding lectin (MBL) mediates the innate immune response either through direct opsonisation of microorganisms or through activation of the complement system. There are conflicting data whether MBL deficiency leads to increased susceptibility to infections or not. The aim of this study was to determine if low levels of mannose-binding lectin (MBL) predict sepsis development, sepsis severity and outcome from severe sepsis or septic shock.MethodPatients aged 18 years or more with documented sepsis within 24 h after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Plasma levels MBL were determined in stored samples from health surveys (baseline) and from ICU admission (acute phase). The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined with 1300 ng/mL as cut-off for low levels.ResultsWe identified 148 patients (61.5% women) with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in a health survey, of which 122 also had samples from the acute septic phase. Both high MBL levels in the acute phase (odds ratio [95% confidence interval]) (2.84 [1.20–6.26]), and an increase in MBL levels from baseline to the acute phase (3.76 [1.21–11.72]) were associated with increased risk for in-hospital death in women, but not in men (0.47 [0.11–2.06]). Baseline MBL levels did not predict future sepsis, sepsis severity or in-hospital mortality.ConclusionsAn increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women.

Predictive and Prognostic Value of Ascitic Fluid Mannose Binding Lectin in Patients with Spontaneous Bacterial Peritonitis.

Spontaneous bacterial peritonitis is a common bacterial infection of ascitic fluid, mainly in ascites due to liver cirrhosis. Mannose-binding lectin (MBL) can activate phagocytosis and the complement system. Spontaneous bacterial peritonitis was detected to be higher in MBL deficiency. This study aimed to assess ascitic fluid MBL in liver cirrhosis and spontaneous bacterial peritonitis. Ninety patients with cirrhotic ascites were included. Forty five of them had SBP. Child- Pugh score, Model for End Stage Liver Disease (MELD) and its update (uMELD) scores were used to assess the severity of liver cirrhosis. Ascitic fluid samples were obtained for differentiation of leucocytic count, estimation of albumin, protein, glucose, and serum-ascitic albumin gradient. Ascitic fluid levels of MBL were measured for all patients. SBP was documented if polymorphonuclear leucocytic count ≥250/mm in ascitic fluid. Ascitic fluid MBL level was significantly lower in patients with SBP. MBL had a significant negative correlation with ascitic total leukocytic count (TLC), also with serum creatinine, bilirubin, PT, INR and MELD score among SBP patients. However, it had a significant positive correlation with ascitic protein and with platelets. According to multivariate analysis, fever, TLC, platelets, creatinine, MBL, glucose and polymorphs were independent predictors for SBP development. Ascitic fluid MBL could be a good predictive and prognostic marker in patients with cirrhosis and spontaneous bacterial peritonitis.

The responses of the gut microbiota to MBL deficiency

Mannose-binding lectin (MBL) deficiency is a common innate immune system deficiency, and is associated with exacerbations and increased colonization of some pathogens. However, the response of the gut microbiota, a pivotal factor in host health, to MBL deficiency is not clear. In this study, MBL−/− and wild-type (WT) mice were generated by backcrossing from MBL-A and MBL-C knockout (KO) mice, and fecal samples were collected at different ages (4th, 8th, 12th, 19th and 27th weeks). The gut microbiota was analyzed by high-throughput sequencing with universal 16S rDNA primers (V3-V5 region). The results showed that structural segregation of the gut microbiota occurred at the 8th, 12th, 19th and 27th weeks of age, although there were no significant differences in alpha diversities between MBL−/− and WT mice at different ages. Impressively, in MBL-/- mice, Akkermansia (from the family Verrucomicrobiaceae) were decreased significantly, Lactobacillus (from the family Lactobacillaceae) abundances, Alistipes and Rikenella (both from the family of Rikenellaceae) were always enriched. Network analysis showed that more interactions existed in the gut microbiota from WT mice (33 nodes and 70 edges) than in the gut microbiota from MBL-/- mice (23 nodes and 40 edges). The 16S rDNA function prediction results indicated that the abundances of predicted genes in the “immune system disease”, “metabolic disease” and “nucleotide metabolism” pathways were significantly increased in the MBL-/- mice. In conclusion, this study revealed that the gut microbiota changed in MBL deficient mice, especially at ages older than 4 weeks.

The effectiveness of cryopreserved human plasma replacement therapy in patients with primary mannose-binding lectin deficiency suffering from chronic active herpes virus infection

The effectiveness of cryopreserved human plasma replacement therapy in patients with primary mannose-binding lectin deficiency suffering from chronic active herpes virus infection

Complement Activation in 22q11.2 Deletion Syndrome

The 22q11.2 deletion syndrome (22q11.2 del), also known as DiGeorge syndrome, is a genetic disorder with an estimated incidence of 1:3000 to 1:6000 births. These patients may suffer from affection of many organ systems with cardiac malformations, immunodeficiency, hypoparathyroidism, autoimmunity, palate anomalies, and psychiatric disorders being the most frequent. The importance of the complement system in 22q11.2 del has not been investigated. The objective of this study was to evaluate the complement system in relation to clinical and immunological parameters in patients. A national cohort of patients (n = 69) with a proven heterozygous deletion of chromosome 22q11.2 and a group of age and sex matched controls (n = 56) were studied. Functional capacity of the classical, lectin, and alternative pathways of the complement system as well as complement activation products C3bc and terminal complement complex (TCC) were accessed and correlated to clinical features. All patients in our study had normal complement activation in both classical and alternative pathways. The frequency of mannose-binding lectin deficiency was comparable to the normal population. The patients had significantly raised plasma levels of C3bc and a slight, but not significant, increase in TCC compared with controls. This increase was associated with the presence of psychiatric disorders in patients. The present study shows no complement deficiencies in 22q11.2 deletion syndrome. On the contrary, there are signs of increased complement activation in these patients. Complement activation is particularly associated with the presence of psychiatric disorders.

Impact of mannose-binding lectin 2 gene polymorphisms on disease severity in noncystic fibrosis bronchiectasis in children.

Mannose-binding lectin (MBL) is a complement protein involved in the innate immune system, and is associated with some chronic respiratory diseases including noncystic fibrosis (non-CF) bronchiectasis in adults. The aim of this study was to investigate the frequency of MBL2 gene polymorphisms in children with non-CF bronchiectasis, and the effect of MBL deficiency on disease severity. Fifty children with non-CF bronchiectasis (bronchiectasis group) and 50 healthy controls (control group) were included. The demographic findings, number of acute pulmonary exacerbations in the previous year, airway cultures, pulmonary function tests, and radiologic scores of the bronchiectasis group were recorded. DNA extraction was performed in both groups and MBL2 gene polymorphisms in codons 52, 54, 57 in exon 1 and H/L, Y/X in the promoter region were studied using real-time polymerase chain reaction. Haplotypes were made by genotypes, and MBL serum expression was classified according to the genotypes in the literature. The bronchiectasis group consisted of 23 (46%) patients with primary ciliary dyskinesia, 5 (10%) with primary immunodeficiency diseases, and 22 (44%) with idiopathic bronchiectasis. There were no statistically significant differences between the bronchiectasis and control groups in terms of allele and genotype frequencies of polymorphisms in codons 52, 54, 57 in exon 1 and promoter H/L. However, the YX heterozygote genotype was more frequent in the control group (82%) compared with the bronchiectasis group (50%) (P = .002). The frequency of patients with intermediate serum MBL expression genotype was higher in the bronchiectasis group (20%) than in the control group (0%) (P = .001). In the bronchiectasis group, there were no significant differences in growth, annual pulmonary exacerbation rates in the last year, pulmonary function tests, radiologic scores, and microbiologic findings between low, intermediate, and high-expressing genotypes. In children with non-CF bronchiectasis, MBL genotype was different from healthy controls. MBL deficiency associated only with MBL genotype was not related to disease severity in this group of patients.

No association of complement mannose-binding lectin deficiency with cardiovascular disease in patients with Systemic Lupus Erythematosus

Cardiovascular (CV) morbidity is the major cause of death in patients with Systemic Lupus Erythematosus (SLE). Previous studies on mannose-binding lectin (MBL) gene polymorphisms in SLE patients suggest that low levels of complement MBL are associated with cardiovascular disease (CVD). However, as large studies on MBL deficiency based on resulting MBL plasma concentrations are lacking, the aim of our study was to analyze the association of MBL concentrations with CVD in SLE patients. Plasma MBL levels SLE patients included in the Swiss SLE Cohort Study were quantified by ELISA. Five different CV organ manifestations were documented. Of 373 included patients (85.5% female) 62 patients had at least one CV manifestation. Patients with MBL deficiency (levels below 500 ng/ml or 1000 ng/ml) had no significantly increased frequency of CVD (19.4% vs. 15.2%, P = 0.3 or 17.7% vs. 15.7%, P = 0.7). After adjustment for traditional CV risk factors, MBL levels and positive antiphospholipid serology (APL+) a significant association of CVD with age, hypertension, disease duration and APL+ was demonstrated. In our study of a large cohort of patients with SLE, we could not confirm previous studies suggesting MBL deficiency to be associated with an increased risk for CVD.

Mannose-Binding Lectin and Mannose-Binding Lectin-Associated Serine Protease-2 Genotypes and Serum Levels in Patients with Sporotrichosis.

Mannose-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are important proteins in the lectin pathway of the immune system. Mannose-binding lectin and MASP-2 deficiencies have been reported to be responsible for various fungal infections. We investigated the association of MBL and MASP-2 variants with sporotrichosis in a Chinese population and revealed one rare heterozygous mutation in a disseminated cutaneous patient without immunosuppressive conditions (MASP2, p.156_159dupCHNH). We also found that sporotrichosis patients had decreased levels of MBL and MASP-2 in their serum samples compared with controls. Our findings linked, for the first time, MASP-2 deficiencies with susceptibility to Sporothrix sp.

9. Hypomyopathic dermatomyositis complicated by mannose-binding lectin deficiency

9. Hypomyopathic dermatomyositis complicated by mannose-binding lectin deficiency

Mannose-Binding Lectin Levels in Late-Onset Sepsis in Preterm Infants: Results from a Prospective Study in a Tertiary Care Center

Introduction: This study aimed to determine the association between serum mannose-binding lectin (MBL) levels, gene polymorphisms and late-onset sepsis (LOS) in preterm infants. Methods: Infants with <37 gestational weeks were categorized into two groups according to the presence of LOS during their hospitalization. An MBL level <700 ng/ml was defined as deficiency, <400 ng/ml as severe deficiency. Codon 54 and 57 polymorphisms of MBL2 gene were analyzed. Results: Overall, 153 preterm infants were included. MBL deficiency was found to be more common in the LOS group (p = 0.02). The rate of Gram-negative sepsis was higher in MBL2 variant-type (p = 0.01). In the logistic regression analysis, MBL levels <700 ng/ml were found to have a significant effect on LOS development (odds ratio: 2.692, 95% confidence interval 1.196–5.8, p = 0.02). Conclusions: MBL deficiency is an important risk factor for the development of LOS. Furthermore, there is an association between MBL2 gene polymorphism and Gram-negative sepsis.

Impact of SNPs interplay across the locus of MBL2, between MBL and Dectin-1 gene, on women\u2019s risk of developing recurrent vulvovaginal infections

BackgroundHuman mannose binding lectin (MBL) and dendritic cell-associated C-type lectin-1 (Dectin-1) are the two prototypical PRRs of innate immunity, whose direct role in recurrent vulvovaginal infections (RVVI) defense has been defined. Previously, MBL insufficiency was proposed as a possible risk factor for the rapid progression of RVVI while, Dectin-1 was found to be playing an active role in the defense. However, the complete genetic bases for the observed low MBL levels are still lacking as our previous studies in harmony with others demonstrated the un-expected genotype–phenotype patterns. This suggested the presence of unidentified regulatory variants that may modulate sMBL levels and risk of RVVI. Therefore, the present study was designed for more inclusive locus-wide MBL2 analysis and for the possible non-linear interaction analysis of two PRRs that may impact RVVI susceptibility.MethodsThe present study has extended the previous findings by investigating (1) the role of chosen additional SNPs falling in the 5′ near region relating to sMBL levels and RVVI susceptibility, using polymerase chain reaction-restriction fragment length polymorphism, (2) interactions among SNPs within gene by comprehensive locus-wide haplotype analyses of two MBL2 blocks, (3) gene–gene interaction analyses between two PRRs, using multifactor dimensionality reduction.Resultsrs11003124_G, rs7084554_C, rs36014597_G, and rs11003123_A were observed as the minor alleles in the representative North Indian cohort. RVVI cases and its types showed an appreciably high frequency of C allele, its homozygosity and heterozygosity, explaining the observed dominant mode of inheritance of rs7084554 polymorphism in contributing 1.81 fold risk of RVVI. The rs36014597 polymorphism showed the overdominant mode of inheritance, which further depicts that the carrier of a heterozygous genotype of this polymorphism had more extreme phenotype than either of its homozygous carriers in developing 4.07 fold risk of RVVI. sMBL levels significantly varied for rs11003124, rs36014597 and rs11003123 polymorphisms in bacterial vaginosis, while for rs7084554 polymorphism in mixed infection. Independent analysis of 5′ and 3′ haplotype blocks suggested the risk-modifying effect of all the 5′ additional variants, Y/X secretor polymorphism and 3′-UTR SNP i.e. rs10824792. Combined 5′/3′ haplotype analyses depicted the importance of rs36014597; an additional 5′ variant, Y/X and rs10824792 polymorphisms from both the blocks in regulating sMBL levels and RVVI risk. Three gene–gene interaction models involving uni-variant, bi-variant and tri-variant appeared as significant predictors of RVVI risk with cross-validation consistency of 10/10, 9/10 and 5/10, respectively.ConclusionsThe study presented a low-cost reproducible screening design for additional 5′ variants i.e. rs11003124, rs7084554, rs36014597 and rs11003123 of MBL2 that can act as markers of susceptibility for RVVI or any other diseases. Two additional 5′ variants of MBL2 i.e. rs7084554 and rs36014597 were suggested as novel molecular markers that may contribute to RVVI risk by varying sMBL levels. Variants of two blocks were found to have more of a combined effect than the independent effect in modulating RVVI susceptibility and sMBL levels. The study presented weak synergistic interaction between MBL2 and CLEC7A in association with RVVI risk. The preliminary data will establish the foundation for the investigation of within gene and between genes interaction analyses towards RVVI susceptibility.

Mannose-binding lectin gene polymorphism and its effect on short term outcomes in preterm infants

ObjectiveMannose-binding lectin, which belongs to the collectin family, is an acute-phase reactant that activates the complement system. This study aimed to investigate the effect of MBL2 gene polymorphism on short-term outcomes in preterm infants. MethodInfants of <37 gestational weeks who were admitted to the neonatal intensive care unit during a two-year period were enrolled in this prospective study. The neonates were categorized into two groups according to their MBL2 genotypes. Normal MBL2 genotype was defined as MBL2 wild-type (AA genotype), whereas mutant MBL2 genotype was defined as MBL2 variant-type (AO/OO genotype). The relationship between MBL2 genotype and short-term morbidity and mortality was evaluated. ResultsDuring the two-year study period, 116 preterm infants were enrolled in this study. In MBL2 variant-type, mannose-binding lectin levels were significantly lower and incidences of mannose-binding lectin deficiency (MBL level<700ng/mL) were higher (p<0.001). In this group, the prevalence of respiratory distress syndrome and mortality was significantly higher (p<0.001, p=0.03 respectively). In the MBL2 wild-type group, the prevalence of necrotizing enterocolitis (NEC) was higher (p=0.01). Logistic regression analyses revealed that MBL2 variant-type had a significant effect on respiratory distress syndrome development (odds ratio, 5.1; 95% confidence interval, 2.2–11.9; p<0.001). ConclusionsMBL2 variant-type and mannose-binding lectin deficiency are important risk factors for respiratory distress syndrome development in preterm infants. Additionally, there is an association between MBL2 wild-type and NEC. Further studies on this subject are needed.

The impact of mannose-binding lectin polymorphisms on lung function in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a congenital lung disease that leads to recurrent and chronic lung infection. The resulting inflammation causes lung damage and declines in lung function. Mannose-binding lectin (MBL) is a first line host defense protein of importance for the innate immunity. Polymorphisms in the MBL gene named MBL2 result in unstable and low functional levels MBL proteins. MBL insufficiency is linked to an increased risk of lung infection and to declines in lung function in patients with cystic fibrosis. We investigated whether there is a similar link in patients with PCD. This retrospective longitudinal study included 85 patients with PCD. Diagnostics and age at diagnosis were recorded, complete spirometry data starting at diagnosis, and Pseudomonas aeruginosa infection status over the last 2 years were collected, and the patients were grouped according to MBL2 genotype status (MBL2-sufficient or MBL2-deficient). MBL-deficient patients were diagnosed almost 3 years earlier than MBL-sufficient patients (median 6.1 vs 8.9 years, P < 0.05). There were no differences in the first measured spirometry values, but MBL-deficient patients showed greater declines in forced expiratory volume in one sec (FEV1 ) than patients with MBL sufficiency (z-score: -0.049 per year [95% CI, -0.075; -0.021] vs -0.009 per year [95% CI, -0.033; 0.015]; P = 0.023). No differences were found in forced vital capacity (FVC), FEV1 /FVC, or infection status. MBL-deficiency, which is associated with MBL2 mutations, was associated with a lower age at diagnosis and with steeper declines in FEV1 in patients with PCD. This suggests that the MBL genotype might be a disease modifier in PCD.

Undetectable mannose binding lectin is associated with HRCT proven bronchiectasis in rheumatoid arthritis (RA).

AimThe aim of this study was to ascertain whether mannose binding lectin deficiency is implicated in coexistent rheumatoid arthritis and bronchiectasis and to determine whether undetectable mannose binding lectin confers poorer long-term survival in coexistent rheumatoid arthritis and bronchiectasis or in rheumatoid arthritis in general.Materials and methodsA retrospective audit was conducted in a rheumatoid arthritis cohort in which mannose binding lectin had been measured by enzyme linked immunosorbent assay from 2007–11. Rheumatoid arthritis patients with physician diagnosed HRCT proven bronchiectasis were recruited during this time and compared to those with uncomplicated rheumatoid arthritis. Survival from disease onset was recorded in October 2018. Kaplan-Meier survival estimates were performed to assess mortality over time in the two groups. Log rank tests were used for equality of survivor functions.ResultsThe two groups were demographically comparable. A higher frequency of undetectable mannose binding lectin was observed in coexistent rheumatoid arthritis and bronchiectasis (37.5%) compared to uncomplicated rheumatoid arthritis, (8.9%, P = 0.005). Undetectable mannose binding lectin correlated with a strong trend toward poor survival in rheumatoid arthritis overall (P = 0.057). Cox regression analysis however, showed no difference in the hazard ratio for survival between the two groups when corrected for age, gender, prednisolone use ever, rheumatoid factor status and the full range of MBL concentrations.ConclusionIn summary, undetectable mannose binding lectin is associated with coexistent rheumatoid arthritis and bronchiectasis and correlates with poor survival in rheumatoid arthritis overall. These findings further implicate immunodeficiency in the genesis of bronchiectasis in rheumatoid arthritis.

Characteristics of Mannose-Binding Lectin Deficiency in Pediatric Septic Patients – Case Presentation

Characteristics of Mannose-Binding Lectin Deficiency in Pediatric Septic Patients – Case Presentation

The role of Mannose Binding Lectin in the immune response against Borrelia burgdorferi sensu lato

The causative agents of Lyme borreliosis, spirochetes belonging to the Borrelia burgdorferi sensu lato group, have developed several ways to protect themselves against killing by the host complement system. In addition, it has been shown that serum sensitive isolates are (partially) protected by the Ixodes Tick Salivary Lectin Pathway Inhibitor (TSLPI) protein; a salivary gland protein that inhibits the function of Mannose Binding Lectin (MBL). MBL is a C-type lectin that recognizes oligosaccharides on pathogens and activates the complement system via the lectin pathway. MBL deficiency has been linked to a more severe course of several infectious diseases and humans with detectable antibodies against B. burgdorferi are significantly more often MBL deficient compared to humans without antibodies against B. burgdorferi. Here we set out to investigate the role of MBL in the immune response against B. burgdorferi in more detail. We demonstrate that B. burgdorferi N40 needle-infected C57BL/6 MBL deficient mice harbored significantly higher B. burgdorferi numbers in skin tissue during the early course of infection. In line with these findings they also developed higher anti-B. burgdorferi IgG serum antibodies compared to WT controls. In contrast, B. burgdorferi loads in distant tissue such as heart, joints or bladder at later time points were similar for both mouse strains. These in vivo findings were corroborated using a B. burgdorferi N40-infected I. scapularis infestation model. We showed that MBL is capable of binding B. burgdorferi through its carbohydrate recognition domains, but in vitro complement killing assays, peritoneal macrophage and whole blood stimulations, phagocytosis assays and an in vivo migration experiment did not reveal the mechanism by which MBL facilitates early clearance of B. burgdorferi. To conclude, we show a protective role of MBL in the early stages of B. burgdorferi infection, yet the underlying mechanism warrants further investigation.

Use of Mannose-Binding Lectin Gene Polymorphisms and the Serum MBL Level for the Early Detection of Neonatal Sepsis.

Background Mannose-binding lectin (MBL) is a component of innate immunity and is particularly important in neonates, in whom adaptive immunity has not yet completely developed. MBL deficiency and MBL2 gene polymorphisms are associated with an opsonization defect and have been associated with neonatal sepsis. Aim The aim of our study was to assess serum MBL levels and genotype MBL2 genes to determine whether they can serve as markers for predicting neonatal sepsis in neonatal intensive care units. Patients and Methods A case-control study was conducted with 114 neonates classified into two groups: the septic group included 64 neonates (41 preterm and 23 full-term infants), and the non-septic control group included 50 neonates (29 preterm and 21 full-term infants). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to genotype MBL2 gene exon 1 (rs1800450) and (rs1800451) SNPs. Enzyme-linked immunosorbent assay (ELISA) was used to measure MBL serum concentrations. Results The polymorphic genotypes BB and AC at codons 54 and 57, respectively, showed higher frequencies than the wild-type genotype (AA) (14.1% versus 12.9% and 28.1% versus 19.4% respectively) in both groups, and this difference was greater in the septic group than in the non-septic group; however, the differences did not reach statistical significance. The B and C allele frequencies were also higher in the septic group than in the non-septic group, but the differences did not reach statistical significance ( p = 0.282 and 0.394, respectively). The serum levels of MBL were significantly lower in the septic group than in the non-septic group ( p = 0.028). Conclusion This study found no association between MBL levels or MBL2 exon 1 genotypes or alleles and neonatal sepsis risk. Further studies with larger sample sizes are needed to determine the role of the MBL2 gene as a risk factor and early predictor of neonatal sepsis.