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OBJECTIVE: Hashimoto's thyroiditis (HT) was described many years ago, but the etiopathogenesis remains unclear. Mannose-binding lectin (MBL) initiates complement activation in the lectin pathway. We determined MBL levels in children with HT and the associations thereof with thyroid hormone and thyroid autoantibody levels. METHODS: Thirty-nine patients with HT and 41 controls were enrolled from the pediatric outpatient clinics. Subjects were grouped according to their thyroid functions: Euthyroid, marked hypothyroidism and clinical/subclinical hyperthyroidism. MBL levels were compared among these groups. Serum MBL levels of the subjects were determined using MBL Human ELISA kit. RESULTS: Serum MBL levels were studied in serum samples from the 80 subjects (48 (60.0%) females). MBL levels in HT and control groups were 50.787±34.718 and 50.593±44.28 ng/ml (p=0,983), respectively. In HT group, there was no significant difference in MBL levels between thyroid function groups (p=0.869). In addition, gender was not detected as a factor for serum MBL levels. Also we found negative correlation between WBC and serum MBL levels (r=-0.532; p=0.050). Otherwise there was no correlation between TSH, anti-TPO and anti-TG with serum MBL levels. CONCLUSION: MBL levels did not decrease in HT patients. Further research is needed to elucidate more fully any role for MBL in the development of autoimmune thyroid disease. [ABSTRACT FROM AUTHOR]

Abstract Background Mannose binding lectin (MBL) has been suggested to be associated with an impaired cardiovascular prognosis in dysglycaemic conditions, but results are still contrasting. Our aims are (i) to examine whether MBL levels differ between patients with an acute myocardial infarction (MI) and healthy controls and between subgroups with different glucose tolerance status, and (ii) to investigate the relation between MBL and future cardiovascular events. Methods MBL levels were assessed at discharge and after 3 months in 161 AMI patients without any previously known glucose perturbations and in 183 age- and gender-matched controls from the Glucose metabolism in patients with Acute Myocardial Infarction (GAMI) study. Participants were classified as having dysglycaemia, i.e. type 2 diabetes or impaired glucose tolerance, or not by an oral glucose tolerance test. The primary outcome was a composite of cardiovascular events comprising cardiovascular death, AMI, stroke or severe heart failure during 11 years of follow-up. Total and cardiovascular mortality served as secondary outcomes. Results At hospital discharge patients had higher MBL levels (median 1246 μg/L) than three months later (median 575 μg/L; p

Introduction: Mannose Binding Lectin (MBL) is a pattern recognizing molecule in the Lectin complement pathway and acts by activating the complement cascade via binding with ligands. There is evidence of increased autoreactivity of Mannose Binding Lectin in various diseases especially diabetes. MBL deficiency can reduce pathogen clearance and impair atherogenic lipoprotein removal whereas higher levels are associated with exaggerated immune response due to complement activation in the presence of hyperglycemia. Aims & Objectives: This study aims to find out the association of MBL (Mannose Binding Lectin) with different clinical parameters in healthy controls and type 2 DM patients to predict disease outcome in type 2 diabetics. Mean level of MBL in type 2 diabetics and healthy population will be compared to characterize MBL levels amongst diabetics helping the clinicians to stratify patients according to disease severity. Place and duration of study: It was a cross sectional analytical study conducted at Chughtai Institute of Pathology from July 2019 to January 2020 on samples collected nationwide at Chughtai Lab collection centres. Material & Methods: We selected 300 adult male and females in this study after taking informed consent based on strict inclusion and exclusion criteria. Of these 200 were known cases of type 2 diabetes mellitus and 100 healthy controls. .Fasting blood samples were drawn from both groups were analyzed for hs-CRP, HbA1c, creatinine, Total Cholesterol, Alanine amino transfer as (ALT), HDL-Cholesterol, LDL-Cholesterol, Glucose, Triglyceride, and Mannose Binding lectin. eGFR (Estimated Glomerular Filtration rate) was calculated for each patient and control. Data was analyzed via Graph Pad Prism 5 and SPSS version 23.0, p value ? 0.05 was taken as significant. Results: Mean age of the participants was 47.9 years in diabetic group and 39.3 years in healthy controls. The healthy population had a mean MBL level of 110.1 (SD±3.94) pg/ml and mean MBL level of diabetic group was 197.9 (SD±12.84) pg/ml (p

Objectives: To evaluate the relationship between mannose-binding lectin (MBL) polymorphism and neonatal sepsis to provide ideas for early diagnosis and control of neonatal sepsis using meta-analysis. Methods: The China National Knowledge Infrastructure, WanFang Data, China Biological Medicine Disc, PubMed, Embase, Cochrane Library, and Web of Science databases were electronically searched to collect studies on the association between the MBL gene variants and the risk of neonatal sepsis. Original articles from case-control and cohort studies on the relationship between MBL polymorphisms and neonatal sepsis were considered eligible. Meta-analysis was performed using Stata 15.0 software. The chi-square-based Q test and I2 statistics were used to assess heterogeneity. Forest plots were used to display the results graphically. Potential publication bias was assessed using the Egger and Begg tests and funnel plots. Results: Twenty-two studies, including 4565 cases and 12,746 controls, were included in this meta-analysis. Meta-analysis showed a significant relationship between MBL rs1800450 (codon 54, G > A) and neonatal sepsis in the variant vs. wild types. However, the analysis showed MBL exon 1 gene polymorphism (A/O), MBL rs5030737 (codon 52, C > T), and rs1800451 (codon 57, G > A), involved in existing research, were not associated with the risk of sepsis in neonates. Conclusions: Current evidence shows that MBL rs1800450 is associated with neonatal culture-proven sepsis. Owing to the limited quantity and quality of the included studies, more high-quality studies are required to verify the above conclusion.

OBJECTIVE: Mannose-binding lectin (MBL) is one of the important parts of the complement system. In our study, we aimed to determine serum MBL levels and their relationship with intensive care hospitalization. PATIENTS AND METHODS: Ninety COVID-19-positive patients from outpatient clinics and clinics were included in this study. The patients were evaluated in three groups as mild, moderate, and severe groups. Each group consisted of 30 patients. A venous blood sample was taken once from each patient. Serum MBL, C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, D-dimer, and ferritin levels were measured. RESULTS: The mean serum MBL levels of all patients were 695.46±324.42 ng/mL. One-way ANOVA test resulted in significant differences in serum CRP, LDH, fibrinogen, D-dimer, ferritin, and MBL levels between groups (p<0.05 for all comparisons). Post-hoc Tukey analysis showed significant differences in serum MBL levels between mild and severe groups and moderate and severe groups. CONCLUSIONS: MBL may be used as a prognostic biomarker in COVID-19 patients. Further studies are needed to determine MBL in treatment strategies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a relapsing inflammatory skin condition, in which bacteria, fungi and viruses may colonize the skin and aggravate the condition. Mannosebinding lectin is part of the innate immune system. Polymorphism in the mannose-binding lectin gene can result in deficiency of mannose-binding lectin, which may affect defence against microbes. The aim of this study was to investigate whether polymorphisms in the mannose-binding lectin gene affect the extent of sensitization to common skin microbes, the skin barrier function, or the severity of the disease in a cohort of patients with atopic dermatitis. Genetic testing of mannose-binding lectin polymorphism was performed in 60 patients with atopic dermatitis. The disease severity, skin barrier function, and serum levels of specific immunoglobulin E against skin microbes were measured. In patients with low mannose-binding lectin genotype (group 1) 6 of 8 (75%) were sensitized to Candida albicans, compared to 14 of 22 (63.6%) patients with intermediate mannose-binding genotype (group 2) and 10 of 30 (33.3%) patients with high mannose-binding genotype (group 3). Group 1 (low mannose-binding lectin) was more likely to be sensitized to Candida albicans compared with group 3 (high mannose-binding lectin) (odds ratio 6.34, p-value 0.045). In this cohort of patients with atopic dermatitis, mannose-binding lectin deficiency was associated with increased sensitization to Candida albicans. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a relapsing inflammatory skin condition, in which bacteria, fungi and viruses may colonize the skin and aggravate the condition. Mannose-binding lectin is part of the innate immune system. Polymorphism in the mannose-binding lectin gene can result in deficiency of mannose-binding lectin, which may affect defence against microbes. The aim of this study was to investigate whether polymorphisms in the mannose-binding lectin gene affect the extent of sensitization to common skin microbes, the skin barrier function, or the severity of the disease in a cohort of patients with atopic dermatitis. Genetic testing of mannose-binding lectin polymorphism was performed in 60 patients with atopic dermatitis. The disease severity, skin barrier function, and serum levels of specific immunoglobulin E against skin microbes were measured. In patients with low mannose-binding lectin genotype (group 1) 6 of 8 (75%) were sensitized to Candida albicans, compared to 14 of 22 (63.6%) patients with intermediate mannose-binding genotype (group 2) and 10 of 30 (33.3%) patients with high mannose-binding genotype (group 3). Group 1 (low mannose-binding lectin) was more likely to be sensitized to Candida albicans compared with group 3 (high mannose-binding lectin) (odds ratio 6.34, p-value 0.045). In this cohort of patients with atopic dermatitis, mannose-binding lectin deficiency was associated with increased sensitization to Candida albicans.

Background: Mannose binding lectin (MBL) has been suggested to be associated with an impaired cardiovascular prognosis in dysglycaemic conditions, but results are still contrasting. Our aims are (i) to examine whether MBL levels differ between patients with an acute myocardial infarction (MI) and healthy controls and between subgroups with different glucose tolerance status, and (ii) to investigate the relation between MBL and future cardiovascular events. Methods: MBL levels were assessed at discharge and after 3 months in 161 AMI patients without any previously known glucose perturbations and in 183 age- and gender-matched controls from the Glucose metabolism in patients with Acute Myocardial Infarction (GAMI) study. Participants were classified as having dysglycaemia, i.e. type 2 diabetes or impaired glucose tolerance, or not by an oral glucose tolerance test. The primary outcome was a composite of cardiovascular events comprising cardiovascular death, AMI, stroke or severe heart failure during 11 years of follow-up. Total and cardiovascular mortality served as secondary outcomes. Results: At hospital discharge patients had higher MBL levels (median 1246 μg/L) than three months later (median 575 μg/L; p < 0.01), the latter did not significantly differ from those in the controls (801 μg/L; p = 0.47). MBL levels were not affected by dysglycaemia either in patients or controls. Independent of glycaemic state, increasing MBL levels did not predict any of the studied outcomes in patients. In unadjusted analyses increasing MBL levels predicted cardiovascular events (hazard ratio HR: 1.67, 95% confidence interval CI 1.06–2.64) and total mortality (HR 1.53, 95% CI 1.12–2.10) in the control group. However, this did not remain in adjusted analyses. Conclusions: Patients had higher MBL levels than controls during the hospital phase of AMI, supporting the assumption that elevated MBL reflects acute stress. MBL was not found to be independently associated with cardiovascular prognosis in patients with AMI regardless of glucose state. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus-1 (HIV-1) enters the brain early during infection and leads to severe neuronal damage and central nervous system impairment. HIV-1 envelope glycoprotein 120 (gp120), a neurotoxin, undergoes intracellular trafficking and transport across neurons; however mechanisms of gp120 trafficking in neurons are unclear. Our results show that mannose binding lectin (MBL) that binds to the N-linked mannose residues on gp120, participates in intravesicular packaging of gp120 in neuronal subcellular organelles and also in subcellular trafficking of these vesicles in neuronal cells. Perinuclear MBL:gp120 vesicular complexes were observed and MBL facilitated the subcellular trafficking of gp120 via the endoplasmic reticulum (ER) and Golgi vesicles. The functional carbohydrate recognition domain of MBL was required for perinuclear organization, distribution and subcellular trafficking of MBL:gp120 vesicular complexes. Nocodazole, an agent that depolymerizes the microtubule network, abolished the trafficking of MBL:gp120 vesicles, suggesting that these vesicular complexes were transported along the microtubule network. Live cell imaging confirmed the association of the MBL:gp120 complexes with dynamic subcellular vesicles that underwent trafficking in neuronal soma and along the neurites. Thus, our findings suggest that intracellular MBL mediates subcellular trafficking and transport of viral glycoproteins in a microtubule-dependent mechanism in the neurons.

Warts is the commonest cutaneous manifestation of human papillomavirus (HPV) infection. Intralesional Candida antigen immunotherapy is used for wart treatment. To identify the role of mannose binding lectin (MBL) in susceptibility to HPV infection and to explore the relationship between MBL and response to intralesional Candida antigen immunotherapy of wart. A case-control study was enrolled with 96 participants; 48 wart cases and 48 healthy controls. MBL serum level assay baseline and after six settings of intralesional candida antigen injection was done by ELISA technique. MBL2 gene exon 1 codon 54 polymorphism was detected by using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). A statistically significant difference in MBL serum level between wart cases and controls was found. An association between MBL2 exon1 codon 54 polymorphism and susceptibility to HPV infection and development of warts was proved. Carriage of genotype AB was more frequent wart cases (95.8%) than in controls (20.8%). No statistical significance association could be found between the therapeutic response to Candida antigen immunotherapy in wart cases and MBL as regards its serum level and genotypes. MBL play an important role in host defense against HPV infection [ABSTRACT FROM AUTHOR]

Objectives: Mannose binding lectin (MBL) gene single nucleotide polymorphisms have been associated with systemic lupus erythematosus (SLE) risk with inconsistent results. This study aimed to explore whether MBL2 A\B, A\C, A\D, A\O, L\H and Y\X polymorphisms affected SLE susceptibility. Methods: A meta‐analysis was performed on 20 studies, containing allelic contrast, additive, dominant and recessive models. Odds ratio (OR) was calculated to reflect the effect of association. Results: A total of 64 pooled comparisons were conducted, including 7194 SLE patients and 7401 healthy controls. The meta‐analysis inducted a significant association between allele B and SLE (OR = 0.766, 95% CI = 0.681‐0.862, P <.001). The genotype BB in the additive model and AB + BB in the recessive model both reduced the risk of SLE (OR = 0.611, 95% CI = 0.422‐0.882, P =.009; OR = 0.806, 95% CI = 0.688‐0.944, P =.008). Regarding A\O polymorphisms, results revealed statistical differences in allelic contrast, additive model and recessive models (OR = 0.826, 95% CI = 0.732‐0.931, P =.002; OR = 0.737, 95% CI = 0.557‐0.977, P =.034 and OR = 0.793, 95% CI = 0.683‐0.921, P =.002, respectively). As for L\H, meta‐analysis revealed that allele H and genotype HH both decreased SLE susceptibility in allelic contrast and dominant models (OR = 1.463, 95% CI = 1.097‐2.007, P =.018; OR = 1.383, 95% CI = 1.124‐1.701, P =.002). Stratification by ethnicity indicated that allele H related to SLE in European populations (OR = 0.736, 95% CI = 0.617‐0.879, P =.001), and the recessive model correlated with SLE in Asians (OR = 0.808, 95% CI = 0.667‐0.979, P =.03). Conclusion: The present study suggests that A\B and A\O polymorphisms were associated with SLE susceptibility, and the allele H may be a protective factor in SLE. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic joint inflammatory condition which can result in damage to the cartilage and bone. RA susceptibility and pathophysiology have been associated with activation of the innate immune pathway. The mannose binding lectin (MBL) activates the complement system and a key component of innate immunity. To study the diagnostic potential of MBL2 genetic variants and flowing serum MBL levels and study their probable function as a marker for RA susceptibility and relation to disease activity. The study included 60 RA patient and 15 age and sex matched control. Detection of MBL serum level and MBL2 gene type and polymorphism by polymerized chain reactin (PCR). The visual analogue-scale (VAS) and disease activity score (DAS28) were assessed. The 60 patients; 51 females and 9 males (F:M 5.7:1) with mean age of 42.2 ± 8.03 years (36–51) and disease duration 5 ± 2.8 (3–7 years). The mean of MBL level in the patients was significantly higher (92.7 ± 78 ng/dl) than in the control (83.8 ± 62.9 ng/dl) (p < 0.01). 33 (55%) had a low level MBL and 27 (45%) moderate level. 14 (93.3%) of the control had low levels and 1 (6.7%) moderate. MBL2 genotype was B (48.3%), D (50%) and C (1.7%) in RA but in the control only 13.3% were positive with type D. The MBL level significantly correlated with the RF (r = 0.3, p = 0.02). There was a strong correlation between MBL2 gene alleles (B and D) and MBL2 protein level and susceptibility for RA in Egyptian populations. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia triggers an acute inflammatory response in the injured brain. Complement activation and neuroinflammation worsen brain damage after a systemic ischemia/reperfusion insult. The increase of mannose binding lectin (MBL) during asphyxia may contribute to the brain damage, via activation of the complement lectin pathway. The possible role of MBL2 gene variants in influencing the severity of post-asphyxia brain injuries is still unexplored. This retrospective study included 53 asphyxiated neonates: 42 underwent therapeutic hypothermia (TH) and 11 did not because they were admitted to the NICU later than 6 h after the hypoxic insult. Blood samples from TH-treated and untreated patients were genotyped for MBL2 gene variants, and biomarker plasma levels (MBL and S100 B protein) were measured at different time points: during hypothermia, during rewarming, and at 7–10 days of life. The timing of blood sampling, except for the T1 sample, was the same in untreated infants. Highest (peak) levels of MBL and MBL2 genotypes were correlated to neuroimaging brain damage or death and long-term neurodevelopmental delay. MBL2 wild-type genotype was associated with the highest MBL levels and worst brain damage on MRI (p = 0.046) at 7–10 days after hypoxia. MBL increased in both groups and S100B decreased, slightly more in treated than in untreated neonates. The progressive increase of MBL (p = 0.08) and to be untreated with TH (p = 0.08) increased the risk of brain damage or death at 7–10 days of life, without affecting neurodevelopmental outcomes at 1 year. The effect of TH on MBL plasma profiles is uncertain.

To analyzes the association between Mannose binding lectin MBL gene and preterm labor, DNA was obtained from peripheral blood of 150 aborted women patients diagnosed as preterm labor and 150 healthy individual have no previous preterm history was extracted. Mannose binding lectin gene was genotyped by PCR-RFLP (Polymerase Chain Reaction – Restriction Fragment Length Polymorphism) method. The data were analyzed by odd ratio (OR) calculation with confidence intervals (CI 95%) and chi square x 2 results were statically analysis. Statistical significant were sent as p value ≤0.05. The allelic frequency between gene and preterm labor group was (94.5) in control compared with (70.7) in patients with significant differences. The homozygous were found to be more than heterozygous (32.3) whereas homozygous AA (43.4) and GG (33.3) with significant differences this work is considered the first study for understanding the correlation between Preterm birth and mannose protein level in Iraq

Abstract Background Host genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of MBL protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections. The aim of this study was to estimate the frequency of alleles, genotypes and haplotypes related to -550, -221 and exon 1 polymorphisms of the MBL2 gene and investigate their association with HHV-8 in people living with HIV/AIDS (PLWHA), as well as the impacts on CD4 cell count and HIV viral load in HIV/HHV-8 coinfected and HIV monoinfected patients. Results A cross sectional study in PLWHA, with and without HHV-8 infection, exploring associations between different factors, was performed in the outpatient infectious and parasitic diseases clinic at a referral hospital. Genomic DNA extractions from leukocytes were performed using a commercial Wizard ® Genomic DNA Purification kit (Promega, Madison, WI). The promoter region (-550 and -221) was genotyped with the TaqMan system (Applied TaqMan Biosystems® genotyping Assays), and the structural region (exon1) was genotyped with Express Sybr Greener Supermix kit (Invitrogen, USA). In total, 124 HIV/HHV-8 coinfected and 213 HIV monoinfected patients were analysed. Median TCD4 counts were significantly lower in HIV/HHV-8 coinfected patients, whereas the mean of the first and last viral load of HIV did not present significant difference. There was no difference in frequency between the LL, YY and AA genotypes between the HIV/HHV-8 coinfected or HIV monoinfected patients. However, in a multivariate analysis, coinfected patients with the intermediate expression haplotype of the MBL2 gene had an odds ratio of 3.1-fold (CI = 1.2–7.6) of their last CD4 cell count being below 350 cells/mm3. Among the coinfected individuals, four developed KS and presented the intermediate expression MBL haplotype, with three being HYA/LXA and one being LYA/LYO. Conclusions Host genetic factors, such as -550, -221 and exon 1 polymorphisms, can be related to the may modify coinfections and/or to the development clinical manifestations caused by HHV-8, especially in HIV/HHV-8 coinfected patients who present the intermediate expression haplotypes of MBL.

The gene sequence encoding the mannose-binding homodimeric protein Allium sativum leaf agglutinin (ASAL) was introduced into maize inbred lines to achieve resistance against sap-sucking corn leaf aphids in transgenic lines. Maize transformants were generated after the co-cultivation of immature maize embryos with the Agrobacterium strain LB4404 harbouring a recombinant Ti-binary ASAL construct driven by the polyubiquitin promoter. The preliminary screening of maize transformants was performed via GUS histochemical analysis, and PCR and Southern blotting confirmed the insertion of the transgene and its stable integration in five transgenic maize lines. Transcript abundance was quantified by a quantitative real-time PCR assay, which revealed variable expression of the ASAL transgene among five transgenic maize lines. The highest mRNA expression of the ASAL gene was found in the A23 transgenic maize line, while the lowest expression was found in the AU1 transgenic maize line. In planta bioassays in the T1 progeny of the transgenic maize lines revealed high resistance against corn leaf aphids compared to the control non-transgenic line. The mortality of the infesting aphids (Rhopalosiphum maidi) was found to vary from 40 to 71% compared to that of the non-transgenic control maize line. [ABSTRACT FROM AUTHOR]

Influenza virus infections cause a wide variety of outcomes, from mild disease to 3 to 5 million cases of severe illness and ~290,000 to 645,000 deaths annually worldwide. The molecular mechanisms underlying these disparate outcomes are currently unknown. Glycosylation within the human host plays a critical role in influenza virus biology. However, the impact these modifications have on the severity of influenza disease has not been examined. Herein, we profile the glycomic host responses to influenza virus infection as a function of disease severity using a ferret model and our lectin microarray technology. We identify the glycan epitope high mannose as a marker of influenza virus-induced pathogenesis and severity of disease outcome. Induction of high mannose is dependent upon the unfolded protein response (UPR) pathway, a pathway previously shown to associate with lung damage and severity of influenza virus infection. Also, the mannan-binding lectin (MBL2), an innate immune lectin that negatively impacts influenza outcomes, recognizes influenza virus-infected cells in a high mannose-dependent manner. Together, our data argue that the high mannose motif is an infection-associated molecular pattern on host cells that may guide immune responses leading to the concomitant damage associated with severity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Anti-HIV chimeric antigen receptors (CARs) promote direct killing of infected cells, thus offering a therapeutic approach aimed at durable suppression of infection emerging from viral reservoirs. CD4-based CARs represent a favored option, since they target the essential conserved primary receptor binding site on the HIV envelope glycoprotein (Env). We have previously shown that adding a second Env-binding moiety, such as the carbohydrate recognition domain of human mannose-binding lectin (MBL) that recognizes the highly conserved oligomannose patch on gp120, increases CAR potency in an in vitro HIV suppression assay; moreover it reduces the undesired capacity for the CD4 of the CAR molecule to act as an entry receptor, thereby rendering CAR-expressing CD8+ T cells susceptible to infection. Here, we further improve the bispecific CD4-MBL CAR by adding a third targeting moiety against a distinct conserved Env determinant, i.e. a polypeptide sequence derived from the N-terminus of the HIV coreceptor CCR5. The trispecific CD4-MBL-R5Nt CAR displays enhanced in vitro anti-HIV potency compared to the CD4-MBL CAR, as well as undetectable HIV entry receptor activity. The high anti-HIV potency of the CD4-MBL-R5Nt CAR, coupled with its all-human composition and absence of immunogenic variable regions associated with antibody-based CARs, offer promise for the trispecific construct in therapeutic approaches seeking durable drug-free HIV remission. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between serum concentration of mannose binding lectin (MBL) and gene polymorphism of promoter region in schizophrenia and its role in immunopathology. Methods: From June 2018 to December 2018, 54 schizophrenics in our hospital were selected as the observation group, and 56 volunteers in our health examination center at the same period were selected as the normal control group. The polymorphism of H/L (-550bp G/C) and X/Y (-221bp C/G) promoter regions of MBL gene was analyzed by PCR-SSP, and the concentration of MBL in serum was detected by ELISA. Results: The serum MBL concentration in the observation group (1367.218± 1277.429) ng/ml was lower than that in the normal control group (1987.781± 976.748) ng/mL, the difference was statistically significant (P<0.05). The frequency of HY/HY genotype in the observation group was lower than the control group (P<0.05), and the frequency of HY/LY genotype was higher than the control group (P<0.05). The serum MBL concentration of HY/HY genotype in the observation group was significantly higher than HY/LX,LY/LX genotype (P<0.05). The serum MBL level of homozygous mutant in the promoter region of MBL gene in the observation group was no significant difference from that in the control group (P>0.05), but the difference of MBL level of MBL genotype heterozygotes was statistically significant (P<0.05). Conclusion: The low level of MBL in schizophrenics is related to the comprehensive regulation of each genotype in the promoter region of MBL gene. The low concentration of MBL is one of the molecular mechanisms for the retention or removal of CIC in schizophrenia. [ABSTRACT FROM AUTHOR]

We covalently attached human immunodeficiency virus type 1 (HIV-1) Env SOSIP trimers to iron oxide nanoparticles (IO-NPs) to create a particulate immunogen for neutralizing antibody (NAb) induction. The attached trimers, ∼20 per particle, retained native-like antigenicity, judged by reactivity with NAbs and non-NAbs. Bivalent (BG505 and B41) trimer IO-NPs were made, as were IO-NPs displaying B41 trimers carrying a PADRE T-cell helper epitope (TCHE). We immunized mice with B41 soluble or IO-NP trimers after PADRE peptide priming. After two immunizations, IO-NP presentation and the TCHE tag independently and substantially increased anti-trimer antibody responses, but titer differences waned after two further doses. Notable and unexpected findings were that autologous NAbs to the N289 glycan hole epitope were consistently induced in mice given soluble but not IO-NP trimers. Various recombinant mannose binding lectins (MBLs) and MBLs in sera of both murine and human origin bound to soluble and IO-NP trimers. MBL binding occluded the autologous NAb epitope on the B41 IO-NP trimers, which may contribute to its poor immunogenicity. The exposure of a subset of broadly active NAb epitopes was also impaired by MBL binding, which could have substantial implications for the utility of trimer-bearing nanoparticles in general and perhaps also for soluble Env proteins. [ABSTRACT FROM AUTHOR]

This study was done to assess the relation between serum mannose binding lectin (MBL) and disease activity and extension in patients with tuberculosis. Methods: The study included 50 pulmonary TB cases recruited from chest department at El Abasia and Tanta Chest Hospitals and 27 patients with other respiratory infections as a positive control group. Also 13 healthy subjects were included as a negative control group. Patients were classified as follows: 30 with active TB (group I), 20 with inactive TB (group II) and 27 with non-TB respiratory diseases as positive control group (group III). Full clinical evaluation, plain chest X-ray (postero-anterior & lateral views), routine laboratory investigations were done to all patients. MBL measurement in serum of all subjects was done by an ELISA assay. Results: No significant difference in MBL levels seen between males and females in all studied groups. MBL levels were significantly higher in group I & II than the other groups. MBL levels were non-significantly higher in active TB (group I) than inactive TB (group II) while they were significantly higher in active TB cases than in infectious respiratory diseases other than TB and non-infectious respiratory diseases. Levels were non-significantly higher in active TB cases than in controls. MBL levels were significantly higher in TB cases than in infectious respiratory diseases other than TB. 60% of active TB group has high MBL level versus 13.3% of non-TB respiratory infection cases and 8.3% of noninfectious respiratory diseases group. Only one patient with far advanced tuberculosis showed significantly higher levels of MBL than patients with minimal and moderate disease while no significant difference seen between patients with minimal and moderately advanced diseases. Conclusion: MBL is possibly related to increased susceptibility to tuberculosis. Its levels were nearly the same in both active and inactive tuberculous patients. There is a direct relation between levels of MBL and disease extension.

Objectives: 1. To identify the variables that are associated with urinary levels of properdin, MBL, C4d, and C5b-9 in patients with idiopathic IgA nephropathy. 2. To analyse whether urinary levels of MBL and/or C4d are useful for identifying the presence of mesangial deposits of C4d/MBL. Patients and method: A total of 96 patients with IgA nephropathy were studied. Demographic, clinical and biochemical variables were recorded at the time of diagnosis. Renal lesions were quantified using the Oxford classification. Immunohistochemical staining for MBL, MASP-2, properdin, C4d, and C5b-9 was performed in kidney biopsies, and in urine, the levels of properdin, MBL, C4d and C5b-9 were determined. Results: In multivariate analysis, the independent predictors of C4d and MBL levels in urine were the mesangial deposits of each protein and, to a lesser extent, the urinary protein excretion. The independent predictors of urinary levels of C5b-9 were MBL properdin and proteinuria. Urinary excretion of C4d had a sensitivity of 90% (95% CI: 58.7–99) and a specificity of 73% (95% CI: 54–87) for detecting mesangial C4d deposits, and the level of MBL had a sensitivity of 83.9% (95% CI: 62–95) and a specificity of 81.6% (95% CI: 65–92) for identifying mesangial deposits of MBL. Conclusion: The main predictor of urinary concentration of C4d and MBL was the presence of their respective mesangial deposits. Urine MBL may contribute to complement activation in the tubular luz through the lectin pathway. Urinary levels of MBL and C4d could be sensitive and specific biomarkers for the identification of patients with mesangial deposits of MBL and C4d.

Background: There is a need to prevent and treat infection in newborns. One approach is administration of antimicrobial proteins and peptides (APPs) such as LL-37, a membrane-active cathelicidin antimicrobial peptide, and mannose-binding lectin (MBL), a pattern-recognition protein that binds to microbial surface polysaccharides resulting in opsonization and complement activation. Low plasma/serum levels of LL-37 and of MBL have been correlated with infection and exogenous administration of these agents may enhance host defense. Methods: The antimicrobial activity of LL-37 (15 µg/ml) or rMBL (0.5, 2 and 10 µg/ml) was tested in hirudin-anticoagulated preterm and term human cord blood (N = 12–14) against Staphylococcus aureus (SA) USA 300 (2x10 4 CFU/ml), Staphylococcus epidermis (SE) 1457 (2x10 4 CFU/ml) and Candida albicans (CA) SC5314 (1x10 4 CFU/ml). After incubation (1, 45, or 180 min), CFUs were enumerated by plating blood onto agar plates. Supernatants were collected for measurement of MBL via ELISA. Results: Preterm cord blood demonstrated impaired endogenous killing capacity against SA and SE compared to term blood. Addition of LL-37 strongly enhanced antimicrobial/antifungal activity vs SA, SE and CA in term blood and SE and CA in preterm blood. By contrast, rMBL showed modest fungistatic activity vs CA in a sub-analysis of term newborns with high basal MBL levels. Baseline MBL levels varied within preterm and term cohorts with no correlation to gestational age. In summary, exogenous LL-37 demonstrated significant antimicrobial activity against SA, SE and CA in term and SE and CA in preterm human blood tested in vitro. rMBL demonstrated modest antifungal activity in term cord blood of individuals with high baseline MBL levels. Conclusions: To the extent that our in vitro results predict the effects of APPs in vivo, development of APPs for prevention and treatment of infection should take into account host age as well as the target pathogen.

Background: Blood cultures, and molecular diagnostic tests that directly detect pathogen DNA in blood, fail to detect bloodstream infections in most infected patients. Thus, there is a need for a rapid test that can diagnose the presence of infection to triage patients, guide therapy, and decrease the incidence of sepsis. Methods: An Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) that uses magnetic microbeads coated with an engineered version of the human opsonin, Mannose Binding Lectin, containing the Fc immunoglobulin domain linked to its carbohydrate recognition domain (FcMBL) was developed to quantify pathogen-associated molecular patterns (PAMPs) in whole blood. This assay was tested in rats and pigs to explore whether it can detect infections and monitor disease progression, and in prospectively enrolled, emergency room patients with suspected sepsis. These results were also compared with data obtained from non-infected patients with or without traumatic injuries. Results: The FcMBL ELLecSA was able to detect PAMPS present on, or released by, 85% of clinical isolates representing 47 of 55 different pathogen species, including the most common causes of sepsis. The PAMP assay rapidly (81%), specificity (>89%), and diagnostic accuracy of 0·87. It also distinguished infection from trauma-related inflammation in the same patient cohorts with a higher specificity than the clinical sepsis biomarker, C-reactive Protein. Conclusion: The FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated. It may help to triage patients with suspected systemic infections, and serve as a companion diagnostic to guide administration of emerging dialysis-like sepsis therapies.

Background and objectives: Bronchial asthma is a heterogeneous, multifactorial pulmonary disease characterized by variable airway obstruction caused by chronic inflammation. Our study investigates the clinical relevance of MBL plasma levels in accordance with IgE values in children who attended a pediatric consult for respiratory symptoms with bronchial asthma. Materials and Methods: The study population consists of patients Results: Our results show significantly different distributions of patients in the bronchial asthma group and control group. The measured values were within the normal range for most controls, while the bronchial asthma patients displayed higher values of plasma MBL and IgE levels. We observed a wider heterogeneity in MBL concentrations in bronchial asthma patients when compared to the healthy age-matched controls. Our results also suggest a potential clinical usefulness of plasma MBL concentrations in accordance with IgE and eosinophil cells levels in the diagnosis of bronchial asthma, and our results may suggest a prognostic role of MBL in the evolution of asthmatic disease; however, further studies are necessary to confirm these findings. Conclusions: We can say that plasma MBL concentrations present a relative diagnostic role for bronchial asthma in pediatric patients and may suggest a more severe disease progression; however, further studies are needed to elucidate the role played by MBL in the determination and evolution of this disease.

Recurrent Vulvovaginal infections (RVVI) are the commonly reported microbiological syndrome affecting millions of women globally. Various molecules of innate immune system are instrumental in clearance of these microbial pathogens, thus suggested as one of the most important contributing factor in determining the disease outcome. Dendritic cell-associated C-type lectin-1 (Dectin-1) is an important molecule of innate immunity that is primarily known for its role in antifungal defenses. However, role of dectin-1 in recognition of other pathogens is also documented. The intracellular expression of dectin-1 was shown to be up-regulated by Mannose Binding Lectin (MBL)-mediated opsonophagocytosis of pathogens. Dectin-1 is encoded by CLEC7A, postulated to be a candidate gene in modulating risk of developing RVVI. In this study, we identified CLEC7A causal variants using in silico analysis. To assess their impact on susceptibility to RVVI, these causal variants along with serum dectin-1 levels (sDectin-1) were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and Enzyme Linked Immnosorbent Assay (ELISA) respectively, under a case-control design. Furthermore, effect of these polymorphisms was also assessed on sMBL levels. In silico analysis revealed 9 putative functional conserved SNPs of CLEC7A. Association analysis revealed a significantly lower risk of developing RVVI and its types in carriers of CLEC7A rs3901533 G allele and its homozygous genotypes (p < 0.05). The heterozygous genotype was associated with significant protection against RVVI (p = 0.004). Haplotypes GGG and GTA showed significant protection against RVVI (p < 0.0001; p = 0.0003), Bacterial Vaginosis (p = 0.03; p = 0.002), Vulvovaginal Candidiasis (p = 0.03; p = 0.01) and Mixed Infections (p = 0.007; p = 0.04). Mean sDectin-1 levels were significantly high in RVVI and its types compared to controls (p < 0.05). Further, genotype-phenotype stratification showed significant differences within/between cases groups and controls. The CLEC7A rs3901533 polymorphism was also found to be associated with sMBL levels. The present study contributed novel insights into the role of dectin-1 in RVVI. CLEC7A rs3901533 polymorphism and high sDectin-1 levels along with low sMBL levels were found to be associated with RVVI susceptibility. Thus, screening of women with RVVI for these novel associations may lead to better diagnosis and treatment. Also genotyping method used in this study constitutes a simple and reliable assay, which can be confidently, used as a cheaper alternative for genotyping these variants in clinical settings. Finally, new restorative markers for other infectious diseases might be found by exploring nine functionally identified CLEC7A SNPs.

Innate recognition of virus proteins is an important component of the immune response to viral pathogens. A component of this immune recognition is the family of lectins; pattern recognition receptors (PRRs) that recognise viral pathogen-associated molecular patterns (PAMPs) including viral glycoproteins. In this review we discuss the contribution of soluble and membrane-associated PRRs to immunity against virus pathogens, and the potential role of these molecules in facilitating virus replication. These processes are illustrated with examples of viruses including human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Ebola virus (EBOV). We focus on the structure, function and genetics of the well-characterised C-type lectin mannose-binding lectin, the ficolins, and the membrane-bound CD209 proteins expressed on dendritic cells. The potential for lectin-based antiviral therapies is also discussed.

To analyzes the association between Mannose binding lectin MBL gene and preterm labor, DNA was obtained from peripheral blood of 150 aborted women patients diagnosed as preterm labor and 150 healthy individual have no previous preterm history was extracted. Mannose binding lectin gene was genotyped by PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) method. The data were analyzed by odd ratio (OR) calculation with confidence intervals (CI 95%) and chi square x ² results were statically analysis. Statistical significant were sent as p value ≤0.05. The allelic frequency between gene and preterm labor group was (94.5) in control compared with (70.7) in patients with significant differences. The homozygous were found to be more than heterozygous (32.3) whereas homozygous AA (43.4) and GG (33.3) with significant differences this work is considered the first study for understanding the correlation between Preterm birth and mannose protein level in Iraq [ABSTRACT FROM AUTHOR]

Background Heart transplantation (HT) is a life-saving treatment for patients with end-stage heart failure. One of the main problems after HT is the humoral response termed antibody-mediated rejection (AMR). Complement activation plays a key role in AMR contributing to graft damage. The aim of this study was to analyze genetic variants in genes related to the complement pathways that could be associated with the development of AMR. Methods Analysis of 51 genes related to the complement pathway was performed by next-generation sequencing in 46 HT recipients, 23 with and 23 without AMR. Statistical analysis was performed with SNPstats and R. Results We identified 2 single nucleotide polymorphisms, 1 in the mannose-binding lectin 2 gene (p.Gly54Asp- MBL2 ) and 1 in the complement factor properdin gene (p.Asn428(p=)- CFP ), that showed significant association with the absence and development of AMR, respectively. Moreover, the presence of the rare allele in p.Gly54Asp- MBL2 control patients correlated with an immunodeficiency of mannose-binding lectin (6.24 ng/ml vs 207.50 ng/ml, p < 0.01), whereas the presence of the rare allele p.Asn428(p=)- CFP in patients with AMR correlated with higher levels of properdin protein (14.65 μg/ml vs 10.77 μg/ml, p < 0.05). Conclusions AMR is a complex phenotype affected by many recipient factors. Variants in p.Gly54Asp- MBL2 and p.Asn428(p=)- CFP genes, encoding mannose-binding lectin 2 and properdin, may influence the risk of AMR. [ABSTRACT FROM AUTHOR]

Recurrent Vulvovaginal infections (RVVI) are the commonly reported microbiological syndrome affecting millions of women globally. Various molecules of innate immune system are instrumental in clearance of these microbial pathogens, thus suggested as one of the most important contributing factor in determining the disease outcome. Dendritic cell-associated C-type lectin-1 (Dectin-1) is an important molecule of innate immunity that is primarily known for its role in antifungal defenses. However, role of dectin-1 in recognition of other pathogens is also documented. The intracellular expression of dectin-1 was shown to be up-regulated by Mannose Binding Lectin (MBL)-mediated opsonophagocytosis of pathogens. Dectin-1 is encoded by CLEC7A, postulated to be a candidate gene in modulating risk of developing RVVI. In this study, we identified CLEC7A causal variants using in silico analysis. To assess their impact on susceptibility to RVVI, these causal variants along with serum dectin-1 levels (sDectin-1) were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Enzyme Linked Immnosorbent Assay (ELISA) respectively, under a case-control design. Furthermore, effect of these polymorphisms was also assessed on sMBL levels. In silico analysis revealed 9 putative functional conserved SNPs of CLEC7A. Association analysis revealed a significantly lower risk of developing RVVI and its types in carriers of CLEC7A rs3901533G allele and its homozygous genotypes (p < 0.05). The heterozygous genotype was associated with significant protection against RVVI (p = 0.004). Haplotypes GGG and GTA showed significant protection against RVVI (p < 0.0001; p = 0.0003), Bacterial Vaginosis (p = 0.03; p = 0.002), Vulvovaginal Candidiasis (p = 0.03; p = 0.01) and Mixed Infections (p = 0.007; p = 0.04). Mean sDectin-1 levels were significantly high in RVVI and its types compared to controls (p < 0.05). Further, genotype-phenotype stratification showed significant differences within/between cases groups and controls. The CLEC7A rs3901533 polymorphism was also found to be associated with sMBL levels. The present study contributed novel insights into the role of dectin-1 in RVVI. CLEC7A rs3901533 polymorphism and high sDectin-1 levels along with low sMBL levels were found to be associated with RVVI susceptibility. Thus, screening of women with RVVI for these novel associations may lead to better diagnosis and treatment. Also genotyping method used in this study constitutes a simple and reliable assay, which can be confidently, used as a cheaper alternative for genotyping these variants in clinical settings. Finally, new restorative markers for other infectious diseases might be found by exploring nine functionally identified CLEC7A SNPs. [ABSTRACT FROM AUTHOR]

Background aims Chimeric antigen receptors (CARs) offer great potential toward a functional cure of human immunodeficiency virus (HIV) infection. To achieve the necessary long-term virus suppression, we believe that CARs must be designed for optimal potency and anti-HIV specificity, and also for minimal probability of virus escape and CAR immunogenicity. CARs containing antibody-based motifs are problematic in the latter regard due to epitope mutation and anti-idiotypic immune responses against the variable regions. Methods We designed bispecific CARs, each containing a segment of human CD4 linked to the carbohydrate recognition domain of a human C-type lectin. These CARs target two independent regions on HIV-1 gp120 that presumably must be conserved on clinically significant virus variants (i.e., the primary receptor binding site and the dense oligomannose patch). Functionality and specificity of these bispecific CARs were analyzed in assays of CAR-T cell activation and spreading HIV-1 suppression. Results T cells expressing a CD4-dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DCSIGN) CAR displayed robust stimulation upon encounter with Env-expressing targets, but negligible activity against intercellular adhesion molecule (ICAM)-2 and ICAM-3, the natural dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin ligands. Moreover, the presence of the lectin moiety prevented the CD4 from acting as an entry receptor on CCR5-expressing cells, including CD8 + T cells. However, in HIV suppression assays, the CD4-DCSIGN CAR and the related CD4-liver/lymph node-specific intercellular adhesion molecule-3-grabbing non-integrin CAR displayed only minimally increased potency compared with the CD4 CAR against some HIV-1 isolates and reduced potency against others. By contrast, the CD4-langerin and CD4-mannose binding lectin (MBL) CARs uniformly displayed enhanced potency compared with the CD4 CAR against all the genetically diverse HIV-1 isolates examined. Further experimental data, coupled with known biological features, suggest particular advantages of the CD4-MBL CAR. Discussion These studies highlight features of bispecific CD4-lectin CARs that achieve potency enhancement by targeting two distinct highly conserved Env determinants while lacking immunogenicity-prone antibody-based motifs. [ABSTRACT FROM AUTHOR]

Mannose binding lectin is a lectin instrumental in the innate immunity. It recognizes carbohydrate patterns found on the surface of a large number of pathogenic micro-organisms, activating the complement system. However, this protein seems to increase the tissue damage after ischemia. In this paper is reviewed some aspects of harmful role of the mannose binding lectin in ischemia/reperfusion injury.

Human immunodeficiency virus-1 (HIV-1) enters the brain early during infection and leads to severe neuronal damage and central nervous system impairment. HIV-1 envelope glycoprotein 120 (gp120), a neurotoxin, undergoes intracellular trafficking and transport across neurons; however mechanisms of gp120 trafficking in neurons are unclear. Our results show that mannose binding lectin (MBL) that binds to the N-linked mannose residues on gp120, participates in intravesicular packaging of gp120 in neuronal subcellular organelles and also in subcellular trafficking of these vesicles in neuronal cells. Perinuclear MBL:gp120 vesicular complexes were observed and MBL facilitated the subcellular trafficking of gp120 via the endoplasmic reticulum (ER) and Golgi vesicles. The functional carbohydrate recognition domain of MBL was required for perinuclear organization, distribution and subcellular trafficking of MBL:gp120 vesicular complexes. Nocodazole, an agent that depolymerizes the microtubule network, abolished the trafficking of MBL:gp120 vesicles, suggesting that these vesicular complexes were transported along the microtubule network. Live cell imaging confirmed the association of the MBL:gp120 complexes with dynamic subcellular vesicles that underwent trafficking in neuronal soma and along the neurites. Thus, our findings suggest that intracellular MBL mediates subcellular trafficking and transport of viral glycoproteins in a microtubule-dependent mechanism in the neurons.