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Summary: Impaired immune response to COVID-19 (coronavirus disease 2019) vaccination has been reported in patients with inborn errors of immunity (IEI). Repetitive vaccinations are recommended for this vulnerable group. Due to the high diversity within IEI patients, additional safety and immunogenicity data are needed to better understand these aspects especially in less common immunodeficiency syndromes. In this prospective open-label clinical trial, we assessed the humoral immune response and the T‑cell response in patients with IEI or severe MBL (mannose-binding lectin) deficiency (IEI/MBLdef) after three vaccinations. A total of 16 patients and 16 matched healthy controls (HC) with suboptimal humoral response defined by anti-SARS-CoV‑2 RBD (severe acute respiratory syndrome coronavirus type 2 receptor binding domain) antibodies below 1500 BAU/ml (binding antibody units per ml) after the second COVID-19 vaccination were enrolled in this study and qualified for a third mRNA vaccine dose. After 4 weeks following vaccination, 100% of HC and 75% of IEI/MBLdef patients exhibited anti-SARS-CoV‑2 RBD antibodies > 1500 BAU/ml, although the difference was not statistically significant (75% vs. 100%; p = 0.109). Although post-vaccination IEI/MBLdef patients demonstrated significantly increased anti-SARS-CoV‑2 RBD antibodies and neutralizing antibodies compared to baseline, these responses were significantly lower in IEI/MBLdef patients compared to HCs. Notably, the third vaccination augmented the cellular immune response to both wild-type and omicron peptide stimulation. No serious adverse events were reported within the 4‑week follow-up period and, importantly, vaccination had little to no effect on the long-term disease activity and fatigue. This trial strongly supports the recommendation of repeated COVID-19 vaccinations for patients suffering from immunodeficiencies, especially when they exhibit an initially limited response to the vaccine. [ABSTRACT FROM AUTHOR]

There is evidence to suggest that M‐type phospholipase A2 (PLA2R) antibodies activate the mannose‐binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy‐confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow‐mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p <.01). MBL levels decreased significantly after immunosuppressive therapy (p =.04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p =.01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients. [ABSTRACT FROM AUTHOR]

Background: The process of tissue injury in coronary artery disease (CAD) has been associated with activation of the complement system, partly due to the action of mannose-binding lectin (MBL) and C3, which are expressed in atherosclerotic lesions. Objective: The aim of this study was to evaluate the serum levels of MBL and C3 in patients with CAD and to compare them with healthy controls. Additionally, we aim to assess the correlation between MBL and C3 levels and cardiometabolic parameters. Methods: MBL and C3 serum concentration were determined by ELISA and immunoturbidimetry, respectively, in up to 119 patients undergoing coronary angiography for CAD evaluation, comprising 48 individuals diagnosed with acute myocardial infarction (MI) and 71 without MI. A total of 93 paired healthy controls were included in the study. Results: Individuals with CAD had MBL serum concentration higher than controls (p =.002), regardless of the presence of MI (p =.006). In addition, high concentration of MBL (>2000 ng/mL) was more frequent in patients with CAD (p =.007; OR = 2.6; 95% CI = 1.3–5.1). C3 levels were not significantly associated with any of the patient groups but were positively correlated with cardiometabolic parameters such as body mass index (BMI) and triglycerides levels. Conclusions: Higher concentrations of MBL were found to be associated with CAD, whereas C3 levels were found to be associated with cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Abstract Background It has been reported that Mannose-binding lectin 2 (MBL2) gene polymorphisms and expression levels are related to dilated cardiomyopathy (DCM). This study aimed to investigate the potential association between MBL2 gene polymorphisms and the pathogenesis of DCM. Methods Five single nucleotide polymorphisms (SNPs) of the MBL2 gene were genotyped in 440 DCM patients and 532 controls in Southwest China. A luciferase reporter assay was used to detect the transcriptional activity the different genotypes. MBL serum levels, left ventricle ejection fraction (LVEF) and lower left ventricular end-diastolic diameter (LVEDD) were measured. Results The rs11003125 C allele increased the transcriptional activity of the MBL2 promoter compared with the rs11003125 G allele. The rs11003125 CC carriers had higher MBL serum levels, LVEF and LVEDD than the rs11003125 CG and GG carriers. Conclusions Our study first revealed that MBL2 polymorphisms and serum MBL levels were associated with DCM. Allele C in rs11003125 of MBL2 may upregulate the expression levels of MBL. High serum MBL levels may be a protective factor in DCM pathogenesis.

The complement lectin pathway is an important means to exert immune effect. Ficolin and Mannan-binding lectin (MBL) are the initiators of complement pathway. Both structure and function are very similar. They can activate the complement path-way by recognizing certain substances on the surface of pathogens, emphasizing phagocytosis or directly kill and dissolve related pathogens, thereby playing an important role in the immune system, especially in fighting infection. The respiratory system diseases are mostly infectious diseases. In recent years, there have been reports that ficolin/MBL is related to many other respiratory diseases. This article discusses the related research of ficolin/MBL and respiratory diseases, hopes to provide theoretical support for related research. [ABSTRACT FROM AUTHOR]

BackgroundFactors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.MethodsWe performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.FindingsThe estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10-8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10-5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10-4).InterpretationWhile multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

The coronavirus disease (Covid-19) pandemic is the most serious event of the year 2020, causing considerable global morbidity and mortality. The goal of this review is to provide a comprehensive summary of reported associations between inter-individual immunogenic variants and disease susceptibility or symptoms caused by the coronavirus strains severe acute respiratory syndrome-associated coronavirus, severe acute respiratory syndrome-associated coronavirus-2, and two of the main respiratory viruses, respiratory syncytial virus and influenza virus. The results suggest that the genetic background of the host could affect the levels of proinflammatory and anti-inflammatory cytokines and might modulate the progression of Covid-19 in affected patients. Notably, genetic variations in innate immune components such as toll-like receptors and mannose-binding lectin 2 play critical roles in the ability of the immune system to recognize coronavirus and initiate an early immune response to clear the virus and prevent the development of severe symptoms. This review provides promising clues related to the potential benefits of using immunotherapy and immune modulation for respiratory infectious disease treatment in a personalized manner.

Introduction:The aim of this study was to investigate the association of mannose-binding lectin (MBL), which is involved in the classical complement pathway in innate immunity, with infections in the autologous hematopoietic stem cell transplantation (AHSCT) process and the frequency of MBL gene polymorphism.Methods:Single gene nucleotide polymorphisms of codons 52 and 54 in exon 1 of the MBL-2 gene were investigated in 30 patients who had received AHSCT with a diagnosis of multiple myeloma in the Adult Bone Marrow Transplant Unit between January 2020 and December 2020. Demographic characteristics, engraftment times, and infectious processes of the patients were recorded.Results:Neutropenic fever developed at least once in 28 (93.3%) patients during AHSCT. During hospitalization pneumonia developed in 6 (20%), urinary tract infection in 4 (13.3%), and catheter infection in 4 (13.3%) patients. MBL gene polymorphism at codon 54 was found in 4 (13.3%) of the patients included in the study. Among the 4 patients with MBL gene polymorphism, 2 had pneumonia and 2 had urinary tract infection (p=0.16 and p=0.07, respectively). There was no difference between the patients with MBL gene polymorphism and those without MBL gene polymorphism in terms of age, gender, and infection type (p>0.05).Conclusion:Bacterial infection was observed in all patients with MBL gene polymorphism during AHSCT. This may be related to the increased susceptibility to infection caused by MBL gene polymorphism. However, in this study no relationship was found between MBL gene polymorphism and infection frequency and type in AHSCT.

Mannose-binding lectin (MBL) binds to SARS-CoV-2, inhibits infection of susceptible cells, and activates the complement system via the lectin pathway. In this study, we investigated the association of MBL2 polymorphisms with the risk of hospitalization and clinical worsening in patients with COVID-19. A total of 550 patients with COVID-19 were included (94 non-hospitalized and 456 hospitalized). Polymorphisms in MBL2 exon 1 (codons 52, 54 and 57) and promoter region (−550, −221, and +4) were determined by real-time PCR. MBL and complement proteins were measured by Luminex. A higher frequency of the H/H genotype and the HYPA haplotype was observed in non-hospitalized patients when compared to hospitalized. In addition, critically ill patients carrying haplotypes associated with high MBL levels (HYPA/HYPA + HYPA/LYPA + HYPA/LYQA + LYPA/LYQA + LYPA/LYPA + LYQA/LYQA + LXPA/HYPA + LXPA/LYQA + LXPA/LYPA) were protected against lower oxygen saturation levels (P = 0.02), use of invasive ventilation use (P = 0.02, OR 0.38), and shock (P = 0.01, OR 0.40), independent of other potential confounders adjusted by multivariate analysis. Our results suggest that variants in MBL2 associated with high MBL levels may play a protective role in the clinical course of COVID-19.

Background: Community-acquired pneumonia (CAP) is one of the most significant childhood diseases worldwide and a leading infectious cause of death in children. This study aimed to evaluate the prognostic value of the inflammatory markers—C-reactive protein (CRP) and procalcitonin (PCT)—and the polymorphic glycoprotein mannose-binding lectin (MBL), deficiency of which is associated with severe infections, in the determination of the optimal type and timing of therapeutic intervention for CAP in childhood. Methods: Retrospective evaluation was conducted on a cohort of 204 children aged 4 months–17 years hospitalized with CAP. Their levels of CRP, PCT, and MBL were assessed for their association with a variety of outcomes, including the incidence of local and systemic complications, admission to the ICU, duration of antibiotic treatment and hospital stay, and death. Results: CRP and PCT proved to be better predictors of complications of CAP than MBL. The area under the curve (AUC) value was highest for PCT as a predictor of systemic complications (AUC = 0.931, 95%CI 0.895–0.967), while CRP (AUC = 0.674, 95%CI 0.586–0.761) performed best as a predictor of local complications (AUC = 0.674, 95%CI 0.586–0.761). Regarding admission to the ICU, CRP was the weakest predictor (AUC = 0.741), while PCT performed the best (AUC = 0.833), followed by MBL (AUC = 0.797). Sensitivity and specificity were calculated for the optimal threshold generated by receiver operating characteristic (ROC) curves, rendering sensitivity of 90% and specificity of 87% for PCT in assessing the risk of systemic complications, compared to sensitivity of 83% and specificity of 90% for CRP. MBL showed relatively high sensitivity (96%) but low specificity (25%) for predicting the need for ICU admission. Conclusions: Early measurement of CRP, PCT, and MBL provides clinicians with important information regarding the course and prognosis of children diagnosed with CAP, thus ensuring prompt, optimal therapeutic management. [ABSTRACT FROM AUTHOR]

Nanotechnology enables investigations of single biomacromolecules, but technical challenges have limited the application in liquid biopsies, for example, blood plasma. Nonetheless, tools to characterize single molecular species in such samples represent a significant unmet need with the increasing appreciation of the physiological importance of protein structural changes at nanometer scale. Mannose-binding lectin (MBL) is an oligomeric plasma protein and part of the innate immune system through its ability to activate complement. MBL also serves a role as a scavenger for cellular debris, especially DNA. This may link functions of MBL with several inflammatory diseases in which cell-free DNA now appears to play a role, but mechanistic insight has been lacking. By making nanoparticle tracking analysis possible in human plasma, we now show that superoligomeric structures of MBL form nanoparticles with DNA. These oligomers correlate with disease activity in systemic lupus erythematosus patients. With the direct quantification of the hydrodynamic radius, calculations following the principles of Taylor dispersion in the blood stream connect the size of these complexes to endothelial inflammation, which is among the most important morbidities in lupus. Mechanistic insight from an animal model of lupus supported that DNA-stabilized superoligomers stimulate the formation of germinal center B cells and drive loss of immunological tolerance. The formation involves an inverse relationship between the concentration of MBL superoligomers and antibodies to double-stranded DNA. Our approach implicates the structure of DNA-protein nanoparticulates in the pathobiology of autoimmune diseases.

Background: malaria caused by Plasmodium falciparum remains a significant and major public health concern in Africa, particularly in hyperendemic regions. Recurrent fevers and high quantities of inflammatory mediators in the circulation define the disease's blood stages. By binding to non-self-pathogen oligosaccharide surfaces, Mannose-Binding Lectin (MBL) and lectin complement pathways trigger innate immune processes and contribute to the formation of adaptive immune responses. Methods: in Sudan, we investigated the varied immune response levels of MBL to the different phases of P. falciparum infection in White Nile and Blue Nile states endemic to malaria. And we looked at the interaction of regulatory Interleukin 6 (IL- 6) cytokines on MBL during infection. Our study was based on a total of 108 cases, in which 86 patients (62.0%) were uncomplicated and (17.6%) were severe, all met the diagnostic criteria and were clinically admitted for malaria infections. For the determination of serum MBL and IL-6 levels, a commercial ELISA kit was employed. Results: the analysis of the results revealed significantly elevated levels of MBL and IL-6 in both severe and uncomplicated cases (p

Mannose-binding lectin (MBL), which is a member of the C-type lectin (CTL) family, plays crucial roles in non-self recognition and the clearance of invading microorganisms. In this study, an MBL (designated as PcMBL) was cloned and characterized from the crayfish Procambarus clarkii. PcMBL cDNA consisted of 816 bp encoding a protein with 271 amino acid residues. The deduced PcMBL contained a signal peptide, three low-complexity regions, and a carbohydrate-recognition domain, as found in most CTLs. The mRNA encoding PcMBL was detected in all the examined tissues. PcMBL expression in hemocytes and intestines was significantly upregulated after stimulation with Vibrio parahaemolyticus and Staphylococcus aureus. RNA interference studies revealed that PcMBL silencing remarkably downregulated the transcription of five antimicrobial peptide genes, namely, Anti-lipopolysaccharide factor 1 (ALF-1), ALF-4, ALF-10, Crustin 1 (Crus-1), and Crus-4. Recombinant PcMBL protein was used for the functional analysis. The results showed that rPcMBL had the capacity to bind to all seven tested microorganisms and three carbohydrates. rPcMBL facilitated the clearance of V. parahaemolyticus and S. aureus and inhibited the formation of biofilms and growth of the two bacteria. In addition, rPcMBL could reduce the mortality of crayfish infected with V. parahaemolyticus or S. aureus. All these results suggest that PcMBL may be involved in immune recognition and pattern elimination in the innate immunity of P. clarkii.

Objective: The purpose of this study is to determine the effects of COVID-19 infection on individuals with mannose binding lectin deficiency. Methods: An electronic medical records search was conducted for MBL deficiency and COVID-19 positive tests from March 2020-August 2022. Individualized chart analysis was conducted and statistical analysis was performed. Results: Thirty-three people in WVU medicine health system carry a diagnosis of mannose binding lectin deficiency and were diagnosed with COVID-19. The mean age of this cohort was 41 years. Seven individuals had severe enough symptoms to lead to an emergency department visit. One person was hospitalized. MBL deficient individuals had 7 times the odds of hospitalization (p =.1506, OR 7.06 (CI 1.117-44.52)) compared to the general public. There was zero mortality among the MBL deficient population. None of the patients reported thrombosis or blood clots. Conclusion: This retrospective cross-sectional analysis of those with known MBL deficiency and COVID-19 infection suggest a lower risk of fatalities and thrombotic events in this cohort. There was however a higher odds ratio of hospitalization compared to the general public, although this was not statistically significant. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the association of mannose-binding lectin (MBL), which is involved in the classical complement pathway in innate immunity, with infections in the autologous hematopoietic stem cell transplantation (AHSCT) process and the frequency of MBL gene polymorphism. Methods: Single gene nucleotide polymorphisms of codons 52 and 54 in exon 1 of the MBL-2 gene were investigated in 30 patients who had received AHSCT with a diagnosis of multiple myeloma in the Adult Bone Marrow Transplant Unit between January 2020 and December 2020. Demographic characteristics, engraftment times, and infectious processes of the patients were recorded. Results: Neutropenic fever developed at least once in 28 (93.3%) patients during AHSCT. During hospitalization pneumonia developed in 6 (20%), urinary tract infection in 4 (13.3%), and catheter infection in 4 (13.3%) patients. MBL gene polymorphism at codon 54 was found in 4 (13.3%) of the patients included in the study. Among the 4 patients with MBL gene polymorphism, 2 had pneumonia and 2 had urinary tract infection (p=0.16 and p=0.07, respectively). There was no difference between the patients with MBL gene polymorphism and those without MBL gene polymorphism in terms of age, gender, and infection type (p>0.05). Conclusion: Bacterial infection was observed in all patients with MBL gene polymorphism during AHSCT. This may be related to the increased susceptibility to infection caused by MBL gene polymorphism. However, in this study no relationship was found between MBL gene polymorphism and infection frequency and type in AHSCT. [ABSTRACT FROM AUTHOR]

Background: Mannose-binding lectin (MBL) is a member of innate immunity and acts with MASP (MBL-associated serine protease) to activate the lectin pathway of the complement system. MBL gene polymorphisms are associated with susceptibility to infectious diseases. This study investigated whether MBL2 genotype, serum MBL levels, and serum MASP-2 levels affect the course of SARS-CoV-2 infection. Methods and results: Pediatric patients diagnosed with COVID-19 by positive real-time polymerase chain reaction (PCR) were included in the study. Single nucleotide polymorphisms in the promoter and exon 1 in the MBL2 gene (rs11003125, rs7096206, rs1800450, rs1800451, rs5030737) were identified by a PCR and restriction fragment length polymorphisms analysis. Serum MBL and MASP-2 levels were measured by ELISA. COVID-19 patients were divided into asymptomatic and symptomatic. Variables were compared between these two groups. A total of 100 children were included in the study. The mean age of the patients was 130 ± 67.2 months. Of the patients, 68 (68%) were symptomatic, and 32 (32%) were asymptomatic. The polymorphisms in the − 221nt and − 550nt promoter regions did not differ between groups (p > 0.05). All codon 52 and codon 57 genotypes were determined as wild-type AA. AB genotypes were found 45.6% in symptomatic patients while 23.5% in asymptomatics. Moreover, BB genotype was detected 9.4% in symptomatic and 6.3% in asymptomatic patients (p < 0.001). B allele was more frequent in symptomatic patients (46.3%) compared to asymptomatic patients (10.9%). (p < 0.001). Serum MBL and MASP-2 levels did not differ statistically between the groups (p = 0.295, p = 0.073). Conclusion: These findings suggest that codon 54 polymorphism in the MBL2 gene exon-1 region can be associated with the symptomatic course of COVID-19. [ABSTRACT FROM AUTHOR]

Background/Aim: The lung-specific soluble lectins, SP-A and SP-D have been clinically used to diagnose interstitial lung disease, but their clinical significance in COVID-19 remains controversial. This study was undertaken to determine their association with other lectins (MBL and FCN1), disease severity, and radiographs in COVID-19 patients. Patients and Methods: A total of 131 patients with COVID-19 admitted in the Sapporo Medical University Hospital between May 22 and September 19, 2021, were enrolled in the study. Data including demographics, medical history, symptoms, signs, laboratory findings, and radiological images were collected from the patients' medical records. Chest computed tomography (CT) scanning was performed at admission. Serum levels of surfactant protein A and D (SP-A and SP-D), mannose-binding lectin (MBL) and ficolin1 (FCN1) were measured using enzymelinked immunosorbent assay (ELISA) kits. Results: Compared to the control group, the COVID-19 group had significantly higher serum SP-A and FCN1 levels on admission (SP-A: 59.60±38.89 vs. 35.61±11.22 ng/ml; p<0.01, FCN1: 542.45±506.04 vs. 250.6±161.1 ng/ml; p<0.01). The severe group in COVID-19 had significantly higher serum SP-D and lower MBL levels than the nonsevere group (SP-D: 141.7±155.7 vs. 61.41±54.54 ng/ml; p<0.01, MBL: 1,670±1,240 vs. 2,170±1,140 ng/ml; p<0.05). SP-D strongly reflected the degree of imaging findings, whereas SP-A showed a significant correlation, albeit slightly weaker than SP-D. Conversely, MBL and FNC1 were not significantly correlated with imaging findings. Conclusion: Among soluble serum lectins, SP-A and SP-D may be more sensitive to CT findings than reported disease biomarkers such as IL-6, LDH, and CRP due to their lungspecific characteristics. [ABSTRACT FROM AUTHOR]

The therapy of advanced mycosis fungoides (MF) presents a therapeutic challenge, and the search for new therapeutic targets is ongoing. Poly(ADP-ribose) polymerase 1 was shown to be upregulated in patients with advanced MF and could be druggable by a new class of chemotherapeutic agents, PARP-1 inhibitors, which are already in clinical trials for other malignancies; however, the role of PARP-1 inhibitors in MF has never been established. We examined the efficacy of talazoparib in the murine model of cutaneous T-cell lymphoma. The cytotoxic effect of talazoparib on Moloney MuLV-induced T-cell lymphoma (MBL2) cells was a result of G2/M cell cycle arrest via the upregulation of p53. The in vivo experiments confirmed the clinical impact of talazoparib on MF tumors. When talazoparib was combined with the histone deacetylase (HDAC) inhibitor, romidepsin, the cytotoxic effect was synergized via downregulation of the DNA-repair genes Fanconianemia complementation group A (FANCA), Fanconi anemia complementation group D2 (FANCD2), and DNA topoisomerase II binding protein 1(TOPBP1)and stimulation of apoptosis via Blimp-1 (PRDM1)/Bax axis. Romidepsin increased the expression of IRF8 and Bcl-6, leading to upregulation of Blimp1and Bax; whereas talazoparib upregulated Blimp-1 and Bax via upregulation of interferon regulatory factor 4 (IRF4), leading to cleavage of caspases 6 and 7. Thus, a combination of talazoparib with romidepsin demonstrated the synergistic antilymphoma effect and warranted further investigation in a clinical trial.

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

Objective: To investigate the role of mannose-binding lectin (MBL) in modulating autophagy and protecting endothelial cells (ECs) from oxidized low-density lipoprotein (ox-LDL)-induced injury. Methods: Serum MBL concentration and carotid intima-media thickness (cIMT) were measured in 94 obese and 105 healthy children. ECs were transfected with MBL over-expression plasmid, LOX1 was knocked-down to explore the protective role of MBL in ox-LDL induced ECs injury. Dendritic cells (DCs) were co-cultured with ECs, and inflammatory factors, DC maturation, and autophagy was assessed. WT and ApoE−/− mice were fed with a high fat diet (HFD) with or without MBL-adenovirus injection for 16 weeks and aortic vascular endothelial tissue was isolated, then atherosclerotic plaque, cell injury and autophagy were analyzed. Results: Serum MBL concentration in obese children was lower than healthy controls and was negatively correlated with cIMT. The uptake of ox-LDL was decreased in LOX1 knock-down ECs. MBL over-expression in vitro inhibited LOX1-ox-LDL binding. Both LOX1 knock-down and MBL over-expression can ameliorate EC autophagy and cell injury. MBL over-expression in vivo alleviated atherosclerotic plaque formation, influenced DC maturation and down-regulated IL-6, IL-12, and TNF-a levels. Conclusions: MBL exerts a protective role in ox-LDL-induced EC injury by modulating DC maturation and EC autophagy via inhibiting LOX1-ox-LDL binding. [ABSTRACT FROM AUTHOR]

Mannose-binding lectin (MBL) is a multifunctional pattern recognition molecule, which not only mediates the recognition of pathogenic microorganisms and their products, playing an important role in innate immune defense, but also participates in adaptive immune responses of mammalian. However, it's related immune mechanism remains limited, especially the regulation of cell proliferation in early vertebrates. In this study, OnMBL was found to bind to kidney macrophages (MФ) from Nile tilapia (Oreochromis niloticus). Interestingly, OnMBL was able to reduce the proliferation of activated-MФ by regulating the cell cycle, arresting a large number of cells in the G0/G1 phase, and increasing the probability of apoptosis. More importantly, we found that the inhibition of cell proliferation by OnMBL was closely related to the evolutionarily conserved canonical transforming growth factor-beta 1 (TGF-β1) signaling pathway. Mechanistically, OnMBL could significantly increase the expression of TGF-β1, activate and regulate the downstream Smad-dependent pathway to reduce the MФ proliferation, thereby maintaining cellular homeostasis in the body's internal environment. This study represents the first description regarding the regulatory mechanisms of the MBL on cell proliferation in teleost fish, which provides a novel perspective on the understanding of the multiple function and evolutionary origins of C-type lectins in the immune system. [ABSTRACT FROM AUTHOR]

Background: malaria caused by Plasmodium falciparum remains a significant and major public health concern in Africa, particularly in hyperendemic regions. Recurrent fevers and high quantities of inflammatory mediators in the circulation define the disease's blood stages. By binding to non-self-pathogen oligosaccharide surfaces, Mannose-Binding Lectin (MBL) and lectin complement pathways trigger innate immune processes and contribute to the formation of adaptive immune responses. Methods: in Sudan, we investigated the varied immune response levels of MBL to the different phases of P. falciparum infection in White Nile and Blue Nile states endemic to malaria. And we looked at the interaction of regulatory Interleukin 6 (IL6) cytokines on MBL during infection. Our study was based on a total of 108 cases, in which 86 patients (62.0%) were uncomplicated and (17.6%) were severe, all met the diagnostic criteria and were clinically admitted for malaria infections. For the determination of serum MBL and IL-6 levels, a commercial ELISA kit was employed. Results: the analysis of the results revealed significantly elevated levels of MBL and IL-6 in both severe and uncomplicated cases (p<0.001). And MBL average in contrast to residents, Blue Nile patients had high parasitemia (599.9 ng/mL) and this difference was statistically significant (p-value<0.05). The remarkable positive correlation of IL-6 serum levels with MBL among malaria patients and healthy controls (r=0.399, p<0.001) was noted too. Conclusions: according to the findings of this study, patients living in hyperendemic areas exhibit a different MBL response rate and appear to be more homogeneous in proportion to the density of P. falciparum due to parasitemia. In addition, it is also dependent on the regulatory immune mediator IL-6. [ABSTRACT FROM AUTHOR]

Background: Mannose-binding lectin (MBL) is an innate immune protein with strong biologic plausibility for protecting against influenza virus-related sepsis and bacterial co-infection. In an autopsy cohort of 105 influenza-infected young people, carriage of the deleterious MBL gene MBL2_Gly54Asp("B") mutation was identified in 5 of 8 individuals that died from influenza-methicillin-resistant Staphylococcus aureus (MRSA) co-infection. We evaluated MBL2 variants known to influence MBL levels with pediatric influenza-related critical illness susceptibility and/or severity including with bacterial co-infections. Methods: We enrolled children and adolescents with laboratory-confirmed influenza infection across 38 pediatric intensive care units from November 2008 to June 2016. We sequenced MBL2 "low-producer" variants rs11003125("H/L"), rs7096206("Y/X"), rs1800450Gly54Asp("B"), rs1800451Gly57Glu("C"), rs5030737Arg52Cys("D") in patients and biologic parents. We measured serum levels and compared complement activity in low-producing homozygotes ("B/B," "C/C") to HYA/HYA controls. We used a population control of 1,142 healthy children and also analyzed family trios (PBAT/HBAT) to evaluate disease susceptibility, and nested case-control analyses to evaluate severity. Results: We genotyped 420 patients with confirmed influenza-related sepsis: 159 (38%) had acute lung injury (ALI), 165 (39%) septic shock, and 30 (7%) died. Although bacterial co-infection was diagnosed in 133 patients (32%), only MRSA co-infection (n = 33, 8% overall) was associated with death (p < 0.0001), present in 11 of 30 children that died (37%). MBL2 variants predicted serum levels and complement activation as expected. We found no association between influenza-related critical illness susceptibility and MBL2 variants using family trios (633 biologic parents) or compared to population controls. MBL2 variants were not associated with admission illness severity, septic shock, ALI, or bacterial co-infection diagnosis. Carriage of low-MBL producing MBL2 variants was not a risk factor for mortality, but children that died did have higher carriage of one or more B alleles (OR 2.3; p = 0.007), including 7 of 11 with influenza MRSA-related death (vs. 2 of 22 survivors: OR 14.5, p = 0.0002). Conclusions: MBL2 variants that decrease MBL levels were not associated with susceptibility to pediatric influenza-related critical illness or with multiple measures of critical illness severity. We confirmed a prior report of higher B allele carriage in a relatively small number of young individuals with influenza-MRSA associated death.

Herewith, we provide novel original data about the prevalence of FCN3 rs532781899 and MASP2 rs72550870 variants among the newborns of aboriginal Siberian Arctic populations (Nenets and Dolgan‐Nganasans) and Russians of East Siberia. This novel data has been analysed along with the genetic data about other proteins of the lectin pathway of the complement system (mannose‐binding lectin and ficolin‐2) obtained earlier. A total of 926 specimens of dried blood spots of the newborns were genotyped. The newborns represented four populations: Nenets, Dolgan‐Nganasans, Mixed aboriginal population, and Russians (Caucasians) to study the prevalence of single nucleotide polymorphisms of FCN3 rs532781899 and MASP2 rs72550870. The prevalence of the deletion allele of the rs532781899 variant in the FCN3 gene associated with the decreased production of ficolin‐3 was found to be increased in Russians compared to the Nenets aboriginal populations (P =.002). The prevalence of the rs72550870*G allele in the MASP2 gene associated with low serum protease activity was found to be increased in Russians compared with Nenets and Dolgan‐Nganasans (P <.001 and P =.03, respectively). The results of the current study and our previous findings corroborate with a hypothesis that human evolution has been directed toward the accumulation of genotypes associated with low activity of the lectin complement activation pathway. [ABSTRACT FROM AUTHOR]

Introduction: It is documented that a series of autoantibodies can be detected with increased frequency in women with recurrent pregnancy loss (RPL) and they may impact the pregnancy prognosis negatively. It is unknown whether the autoantibodies per se or the basic immune disturbances underlying autoantibody production, are the reason for this association. Our group has previously found that some genetically determined immunological biomarkers are associated with RPL and the same biomarkers are also in various degrees known to predispose to autoantibody production. The aim of this study was to clarify whether the RPL-associated immunogenetic biomarkers are associated with positivity for three major classes of autoantibodies associated with RPL. Methods: In 663 patients with RPL in whom we had results for HLA-DRB1 typing and plasma mannose-binding lectin (p-MBL) measurement, it was investigated whether there is a correlation between positivity for the autoantibodies: anticardiolipin antibodies, b2 glycoprotein I antibodies, and lupus anticoagulant (jointly called antiphospholipid antibodies), thyroid-peroxidase antibodies, and antinuclear antibodies and each of the HLA-DRB1 alleles HLA-DRB1*03 or HLADRB1*07 either alone or in combination with low p-MBL defined as ≤500 µg/l. Results: Although slightly higher frequencies of positivity of two or more autoantibodies were seen in patients with either p-MBL ≤500 µg/l or being positive for HLA-DRB1*03, none were significantly associated. However, in patients with the combination of low p-MBL and HLA-DRB1*03, presence of at least one autoantibody was significantly more frequent than in patients with no such combination (OR= 2.4; 95% CI 1.2-5.0, p = 0.01). In an analysis of which autoantibodies were most strongly associated with the low p-MBL/HLA-DRB1*03 combination, antinuclear antibodies were significantly more frequent in these patients (OR 2.0; 95% CI 1.0-3.9, p=0.05) whereas the other autoantibodies were also positively but more weakly associated with this combination. Discussion: In conclusion, to clarify the pathogenetic background, underlying immunogenetic factors should be examined in autoantibody positive RPL patients (as well as other patients with autoimmune diseases) but the genetic background may be complex. [ABSTRACT FROM AUTHOR]

Genetic susceptibility is an essential pathogenetic mechanism in autoimmune thyroid disease (AITD). MBL2 gene polymorphisms have been shown to play a vital role in the pathogenesis of multiple autoimmune disorders, but its contribution to AITD is unclear. The aim of this study was to assess the linkage between MBL2 gene polymorphisms and AITD susceptibility in a Chinese Han population. One thousand seven hundred sixty seven subjects consisting of 965 AITD patients and 802 controls from a Chinese Han population were enrolled in the case–control study. Four common single-nucleotide polymorphisms (SNPs) in the MBL2 gene were tested using high-throughput sequencing technology for sequence-based SNP genotyping. The allele and genotype distribution results showed that the minor alleles of rs198266, rs10824793, and rs4935046 were significantly lower in Hashimoto's thyroiditis (HT) patients than in healthy controls. In further genetic model analysis, the dominant models of rs1982266, rs10824793, and rs4935046 for MBL2 in the AITD group exhibited a lower risk of morbidity. Finally, we discovered that haplotype AAGC was associated with Graves' disease (GD), while AGC was associated with HT. Our study provides strong evidence for a genetic correlation between MBL2 and AITD, and the polymorphism of the MBL2 gene may be a protective factor for AITD, especially for HT. These findings can advance our understanding of the etiology of AITD, as well as provide guidance for prevention and intervention toward AITD. [ABSTRACT FROM AUTHOR]

Background Warts are skin disease caused by human papilloma virus infection and characterized by high rate of recurrence and resistance. The use of purified protein derivatives (PPD) for treatment of warts achieved good results, however, some patients do not respond to it. Deficiency of mannose-binding lectin (MBL) may be a risk for repeated viral infection. Objective To investigate the factors that may affect and predict the clinical response of warts to the treatment with PPD. Patients and methods This study was conducted on 50 patients with warts and 50 apparently healthy-control volunteers. Blood samples from all participants were investigated for the polymorphism in MBL2-gene exon-1 codon 54 by PCR before treatment. All patients were injected intralesionally in the biggest wart every 2 weeks for five sessions. Results About 56% of the patients achieved complete response, 8% attained partial response, and 36% did not show any response. We did not detect recurrence or progression during the follow-up period. There was significantly higher clinical response in patients with less than five warts and in those with warts of less than 1-year duration. There was significantly lower clinical response in patients with warts over the dorsum of hand, while higher clinical response was observed in the warts over the sole. Although higher number (48%) of patients compared with controls showed polymorphism of MBL2 gene, it has no relation of the effect of PPD injection. Conclusion Intralesional immunotherapy with PPD is effective and safe for treatment of warts. Duration, number, and site of warts might have an impact on the clinical response to PPD immunotherapy, while MBL2-gene exon-1 codon-54 polymorphism has no effect. [ABSTRACT FROM AUTHOR]

Abstract Background Leishmaniasis is caused by an intracellular protozoan of the Leishmania genus. Mannose-binding lectin (MBL) is a serum complement protein and recognizes lipoprotein antigens in protozoa and the bacterial plasma membrane. Nucleotide variants in the promoter region and exon 1 of the MBL gene can influence its expression or change its molecular structure. Objective To evaluate, through a systematic review, case-control studies of the genetic association of variants in the MBL2 gene and the risk of developing leishmaniasis. Methods This review carried out a search in PubMed, Science Direct, Cochrane Library, Scopus and Lilacs databases for case-control publications with six polymorphisms in the mannose-binding Lectin gene. The following strategy was used: P = Patients at risk of leishmaniasis; I = Presence of polymorphisms; C = Absence of polymorphisms; O = Occurrence of leishmaniasis. Four case/control studies consisting of 791 patients with leishmaniasis and 967 healthy subjects (Control) are included in this meta-analysis. The association of variants in the mannose-binding Lectin gene and leishmaniasis under the allelic genetic model, -550 (Hvs. L), -221 (X vs. Y), +4 (Q vs. P), CD52 (A vs. D), CD54 (A vs. B), CD57 (A vs. C) and A/O genotype (A vs. O) was evaluated. International Prospective Register of Systematic Reviews (PROSPERO): CRD42020201755. Results The meta-analysis results for any allelic genetic model showed no significant association for the variants within the promoter, the untranslated region, and exon 1, as well as for the wild-type A allele and mutant allele O with leishmaniasis. Study limitations Caution should be exercised when interpreting these results, as they are based on a few studies, which show divergent results when analyzed separately. Conclusions This meta-analysis showed a non-significant association between the rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, and rs1800451 polymorphisms of the Mannose-binding Lectin gene and leishmaniasis in any allelic and heterogeneous evaluation.

Background: The mannose-binding lectin (MBL) plays an important role in innate immunity. Genetically determined variations in serum levels of MBL may influence the susceptibility and clinical outcome of dengue infection in early life. Methods: We investigated the MBL2 gene polymorphisms and serum levels of MBL (total and functional) in children with asymptomatic (n=17) and symptomatic (n=29) primary dengue infections and age-matched uninfected children (n=84) enrolled in a birth cohort with dengue in Brazil. Polymorphisms of the MBL2 gene were assessed by reverse transcription-polymerase chain reaction (RT-PCR), whereas the enzyme-linked immunosorbent assay (ELISA) was used to quantify serum levels of MBL. Results: We found that the X allele and YX genotype in the MBL2 were more frequent in the dengue cases than in the control group. Likewise, the LXPA haplotype was exclusively found in dengue cases, thus probably related to dengue infection in our setting. Moreover, we found a higher frequency of the O allele and AO genotype in the control group. Serum levels of total and functional MBL were higher in dengue naïve infants than in dengue cases. Conclusions: MBL2 variants related to lower production of serum MBL were associated with dengue infection in infants, whereas intermediate to high levels of total and functional serum MBL were associated with protection against dengue infection. These findings highlight the role of MBL2 variants and serum levels of MBL in the susceptibility of children to dengue disease at early ages.

Mannose-binding lectin (MBL) is a vital member of the lectin family, crucial for mediating functions within the complement lectin pathway. In this study, following the cloning of the mannose-binding lectin (MBL) gene in the ridgetail white prawn, Exopalaemon carinicauda , we examined its expression patterns across various tissues and its role in combating challenges posed by Vibrio parahaemolyticus. The results revealed that the MBL gene spans 1342 bp, featuring an open reading frame of 972 bp. It encodes a protein comprising 323 amino acids, with a predicted relative molecular weight of 36 kDa and a theoretical isoelectric point of 6.18. The gene exhibited expression across various tissues including the eyestalk, heart, gill, hepatopancreas, stomach, intestine, ventral nerve cord, muscle, and hemolymph, with the highest expression detected in the hepatopancreas. Upon challenge with V. parahaemolyticus , RT-PCR analysis revealed a trend of MBL expression in hepatopancreatic tissues, characterized by an initial increase followed by a subsequent decrease, peaking at 24 h post-infection. Employing RNA interference to disrupt MBL gene expression resulted in a significant increase in mortality rates among individuals challenged with V. parahaemolyticus. Furthermore, we successfully generated the Pet32a-MBL recombinant protein through the construction of a prokaryotic expression vector for conducting in vitro bacterial inhibition assays, which demonstrated the inhibitory effect of the recombinant protein on V. parahaemolyticus , laying a foundation for further exploration into its immune mechanism in response to V. parahaemolyticus challenges. [Display omitted] • The expression level of the MBL gene was highest in the hepatopancreas of E. carinicauda. • The expression level of the MBL gene was highest at 24 h after V. parahaemolyticus challenge. • Knockdown of MBL expression may lead to a decrease in the ability to resist V. parahaemolyticus. • MBL exhibited a pronounced inhibitory effect against V. parahaemolyticus. [ABSTRACT FROM AUTHOR]

Background: Community-acquired pneumonia (CAP) is one of the most significant childhood diseases worldwide and a leading infectious cause of death in children. This study aimed to evaluate the prognostic value of the inflammatory markers—C-reactive protein (CRP) and procalcitonin (PCT)—and the polymorphic glycoprotein mannose-binding lectin (MBL), deficiency of which is associated with severe infections, in the determination of the optimal type and timing of therapeutic intervention for CAP in childhood. Methods: Retrospective evaluation was conducted on a cohort of 204 children aged 4 months–17 years hospitalized with CAP. Their levels of CRP, PCT, and MBL were assessed for their association with a variety of outcomes, including the incidence of local and systemic complications, admission to the ICU, duration of antibiotic treatment and hospital stay, and death. Results: CRP and PCT proved to be better predictors of complications of CAP than MBL. The area under the curve (AUC) value was highest for PCT as a predictor of systemic complications (AUC = 0.931, 95%CI 0.895–0.967), while CRP (AUC = 0.674, 95%CI 0.586–0.761) performed best as a predictor of local complications (AUC = 0.674, 95%CI 0.586–0.761). Regarding admission to the ICU, CRP was the weakest predictor (AUC = 0.741), while PCT performed the best (AUC = 0.833), followed by MBL (AUC = 0.797). Sensitivity and specificity were calculated for the optimal threshold generated by receiver operating characteristic (ROC) curves, rendering sensitivity of 90% and specificity of 87% for PCT in assessing the risk of systemic complications, compared to sensitivity of 83% and specificity of 90% for CRP. MBL showed relatively high sensitivity (96%) but low specificity (25%) for predicting the need for ICU admission. Conclusions: Early measurement of CRP, PCT, and MBL provides clinicians with important information regarding the course and prognosis of children diagnosed with CAP, thus ensuring prompt, optimal therapeutic management.

IntroductionIt is documented that a series of autoantibodies can be detected with increased frequency in women with recurrent pregnancy loss (RPL) and they may impact the pregnancy prognosis negatively. It is unknown whether the autoantibodies per se or the basic immune disturbances underlying autoantibody production, are the reason for this association. Our group has previously found that some genetically determined immunological biomarkers are associated with RPL and the same biomarkers are also in various degrees known to predispose to autoantibody production. The aim of this study was to clarify whether the RPL-associated immunogenetic biomarkers are associated with positivity for three major classes of autoantibodies associated with RPL.MethodsIn 663 patients with RPL in whom we had results for HLA-DRB1 typing and plasma mannose-binding lectin (p-MBL) measurement, it was investigated whether there is a correlation between positivity for the autoantibodies: anticardiolipin antibodies, β2 glycoprotein I antibodies, and lupus anticoagulant (jointly called antiphospholipid antibodies), thyroid-peroxidase antibodies, and antinuclear antibodies and each of the HLA-DRB1 alleles HLA-DRB1*03 or HLA-DRB1*07 either alone or in combination with low p-MBL defined as ≤500 µg/l.ResultsAlthough slightly higher frequencies of positivity of two or more autoantibodies were seen in patients with either p-MBL ≤500 µg/l or being positive for HLA-DRB1*03, none were significantly associated. However, in patients with the combination of low p-MBL and HLA-DRB1*03, presence of at least one autoantibody was significantly more frequent than in patients with no such combination (OR= 2.4; 95% CI 1.2-5.0, p = 0.01). In an analysis of which autoantibodies were most strongly associated with the low p-MBL/HLA-DRB1*03 combination, antinuclear antibodies were significantly more frequent in these patients (OR 2.0; 95% CI 1.0-3.9, p=0.05) whereas the other autoantibodies were also positively but more weakly associated with this combination.DiscussionIn conclusion, to clarify the pathogenetic background, underlying immunogenetic factors should be examined in autoantibody positive RPL patients (as well as other patients with autoimmune diseases) but the genetic background may be complex.

Invasive microbes causing diseases such as sudden oak death negatively affect ecosystems and economies around the world. The deployment of resistant genotypes for combating introduced diseases typically relies on breeding programs that can take decades to complete. To demonstrate how this process can be accelerated, we employed a genome-wide association mapping of ca 1,000 resequenced Populus trichocarpa trees individually challenged with Sphaerulina musiva, an invasive fungal pathogen. Among significant associations, three loci associated with resistance were identified and predicted to encode one putative membrane-bound L-type receptor-like kinase and two receptor-like proteins. A susceptibility-associated locus was predicted to encode a putative G-type D-mannose-binding receptor-like kinase. Multiple lines of evidence, including allele analysis, transcriptomics, binding assays, and overexpression, support the hypothesized function of these candidate genes in the P. trichocarpa response to S. musiva.

Biosensors detect signals using biological sensing components such as redox enzymes and biological cells. Although cellular versatility can be beneficial for different applications, limited stability and efficiency in signal transduction at electrode surfaces represent a challenge. Recent studies have shown that the Mtr electron conduit from Shewanella oneidensis MR-1 can be produced in Escherichia coli to generate an exoelectrogenic model system with well-characterized genetic tools. However, means to specifically immobilize this organism at solid substrates as electroactive biofilms have not been tested previously. Here, we show that mannose-binding Fim pili can be produced in exoelectrogenic E. coli and can be used to selectively attach cells to a mannose-coated material. Importantly, cells expressing fim genes retained current production by the heterologous Mtr electron conduit. Our results demonstrate the versatility of the exoelectrogenic E. coli system and motivate future work that aims to produce patterned biofilms for bioelectronic devices that can respond to various biochemical signals.

Water occupies typically 50% of a protein crystal and thus significantly contributes to the diffraction signal in crystallography experiments. Separating its contribution from that of the protein is, however, challenging because most water molecules are not localized and are thus difficult to assign to specific density peaks. The intricateness of the protein-water interface compounds this difficulty. This information has, therefore, not often been used to study biomolecular solvation. Here, we develop a methodology to surmount in part this difficulty. More specifically, we compare the solvent structure obtained from diffraction data for which experimental phasing is available to that obtained from constrained molecular dynamics (MD) simulations. The resulting spatial density maps show that commonly used MD water models are only partially successful at reproducing the structural features of biomolecular solvation. The radial distribution of water is captured with only slightly higher accuracy than its angular distribution, and only a fraction of the water molecules assigned with high reliability to the crystal structure is recovered. These differences are likely due to shortcomings of both the water models and the protein force fields. Despite these limitations, we manage to infer protonation states of some of the side chains utilizing MD-derived densities.

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

Objective: To assess the association between the Mannose-binding lectin (MBL) gene polymorphism and the susceptibility to sepsis using a meta-analysis. Methods: The publications were searched on PubMed, Embase, and Web of Science databases up to December 1, 2019 for relevant literature. Results: A total of 32 studies (21 adult and 11 pediatric studies) were selected for analysis. Overall, in the three models of MBL +54 A/B gene polymorphisms, namely the dominant model BB + AB vs. AA (p = 0.03), the recessive model BB vs. AB + AA (p < 0.00001), and the allele model B vs. A (p = 0.04), MBL +54 A/B was significantly related to the risk of sepsis. In the adult group, the MBL A/O gene polymorphism was associated with the risk of sepsis in the dominant model AO + OO vs. AA (p = 0.006) as well as in the allele model O vs. A (p = 0.04). The MBL +54 A/B gene polymorphism was significantly related to the risk of sepsis in the recessive model and, therefore, may increase the risk of sepsis. In the pediatric group, no polymorphic loci were significantly associated with sepsis in any of the three models. The results of the publication bias test demonstrated no publication bias in an unadjusted estimate of the relationship between MBL A/O and −211Y/X gene polymorphism and sepsis. Conclusions: The polymorphisms of MBL that are related to the occurrence of sepsis are primarily A/O and +54 A/B, while −221Y/X and −550H/L have no clear relationship with the susceptibility of sepsis in various age groups or different models. [ABSTRACT FROM AUTHOR]

Lectin is a carbohydrate-binding protein that recognizes specific cells by binding to cell-surface polysaccharides. Tumor cells generally show various glycosylation patterns, making them distinguishable from non-cancerous cells. Consequently, lectin has been suggested as a good anticancer agent. Herein, the anticancer activity of Bryopsis plumosa lectins (BPL1, BPL2, and BPL3) was screened and tested against lung cancer cell lines (A549, H460, and H1299). BPL2 showed high anticancer activity compared to BPL1 and BPL3. Cell viability was dependent on BPL2 concentration and incubation time. The IC50 value for lung cancer cells was 50 μg/mL after 24 h of incubation in BPL2 containing medium; however, BPL2 (50 μg/mL) showed weak toxicity in non-cancerous cells (MRC5). BPL2 affected cancer cell growth while non-cancerous cells were less affected. Further, BPL2 (20 μg/mL) inhibited cancer cell invasion and migration (rates were ˂20%). BPL2 induced the downregulation of epithelial-to-mesenchymal transition-related genes (Zeb1, vimentin, and Twist). Co-treatment with BPL2 and gefitinib (10 μg/mL and 10 μM, respectively) showed a synergistic effect compared with monotherapy. BPL2 or gefitinib monotherapy resulted in approximately 90% and 70% cell viability, respectively, with concomitant treatment showing 40% cell viability. Overall, BPL2 can be considered a good candidate for development into an anticancer agent. [ABSTRACT FROM AUTHOR]

Background: The distinction between infection and flare in systemic lupus erythematosus (SLE) has always been a dilemma for clinicians as the clinical and biochemical profiles overlap. The present study evaluated affordable biomarkers to distinguish infection from flare in an SLE cohort in a tertiary care center in eastern India. Methods: One hundred and fifty-two SLE patients were clinically evaluated and enrolled in the present study. Hematological, immunological, and biochemical profiles and various biomarkers such as C reactive protein (CRP), procalcitonin (PCT), and Mannose-binding lectin (MBL) were quantified. Results: One hundred and fifty-two patients (152) were enrolled in the present study and all had SLEDAI scores of more than 4. From which 70 had infection, and the common infections were urinary tract infection (34.28%) followed by pneumonia (27.14%). Neutrophil–lymphocyte ratio (NLR) and C-reactive protein (CRP) were significantly elevated in SLE with infections (NLR: 5.84 ± 2.47; CRP: 30.56 ± 41.63) than those with flare (NLR: 3.87 ± 2.62; CRP: 8.73 ± 9.53). The receiver operating characteristic curve (ROC) analysis revealed CRP, PLR, and NLR as important markers for predicting infections (CRP: AUC = 0.682, p = 0.0001; PLR: AUC = 0.668, p = 0.0008; NLR: AUC = 0.742, p < 0.0001). The MBL and PCT levels were comparable among SLE flare and those with infections. Conclusions: NLR and CRP levels are affordable biomarkers to distinguish infections from flares in SLE. MBL and PCT could not differentiate flare from an infection. Key Points • Biomarkers for the differentiation of infection and flare in SLE are limited. • NLR, PLR, and CRP are promising biomarkers to enable differentiation. • PCT and MBL are not ideal biomarkers to differentiate infection from flare. [ABSTRACT FROM AUTHOR]

The contribution of the complement system to non-specific host defence and maintenance of homeostasis is well appreciated. Many particulate systems trigger complement activation but the underlying mechanisms are still poorly understood. Activation of the complement cascade could lead to particle opsonisation by the cleavage products of the third complement protein and might promote inflammatory reactions. Antibody binding in a controlled manner and/or sensing of particles by the complement pattern-recognition molecules such as C1q and mannose-binding lectin can trigger complement activation. Particle curvature and spacing arrangement/periodicity of surface functional groups/ligands are two important parameters that modulate complement responses through multivalent engagement with and conformational regulation of surface-bound antibodies and complement pattern-recognition molecules. Thus, a better fundamental understanding of nanometer- and angstrom-scale parameters that modulate particle interaction with antibodies and complement proteins could portend new possibilities for engineering of particulate drug carriers and biomedical platforms with tuneable complement responses and is discussed here. [Display omitted] • Many nano−/micro-particles trigger complement activation in human plasma. • Particle curvature modulates complement responses. • Spacing arrangement/periodicity of surface moieties modulates complement responses. • Refinement of particle size and surface properties overcomes complement activation. [ABSTRACT FROM AUTHOR]

Objective: This study aims to determine the effects of the mannose-binding lectin (MBL) gene polymorphism on the clinical and laboratory findings, response to treatment, and progress of patients with acute post-streptococcal glomerulonephritis (APSGN). Methods: Codon 54 polymorphism found in exon 1 of the MBL gene was investigated by polymerase chain reaction-restriction fragment length polymorphism method in 110 children followed up with the diagnosis of APSGN and compared with healthy control group. Results: The normal allele AA and, the variant alleles AB and BB gene frequencies were determined within the APSGN group as 74.5%, 20% and, 5.5%, respectively. No statistically significant difference was found with concerning to the gene polymorphism in the APSGN group when compared with the control group (p>0.05). No correlation was found in the patient group between gene polymorphism and the presence of hematuria, edema, central nervous system findings, and blood pressure (p>0.05). Concerning laboratory findings during the diagnosis, no correlation existed between the gene polymorphism and high levels of urea, creatine, total cholesterol, and triglycerides, low levels of albumin, and the presence of proteinuria (p>0.05). Within the first years following the diagnosis, no statistically significant difference was found in the glomerular filtration rates, blood creatine levels, proteinuria levels, duration of microscopic hematuria and proteinuria between the patients with the gene polymorphism and those without the gene polymorphism (p>0.05) Conclusion: Our study determined that the MBL gene polymorphism was not important in the development, the laboratory and clinical findings, or the progression of the patients with APSGN.

STUDY QUESTION Are low or high plasma mannose-binding lectin (p-MBL) levels associated with recurrent pregnancy loss (RPL) and the reproductive and perinatal outcomes before and after RPL? SUMMARY ANSWER The prevalence of low p-MBL levels was significantly higher in RPL patients, while high levels were significantly less prevalent. No association was found between p-MBL level and reproductive and perinatal outcomes before and after RPL. WHAT IS KNOWN ALREADY Mannose-binding lectin (MBL) is an important component in the innate immune system. Low p-MBL levels have been associated with RPL, while the correlation with high levels has been poorly studied. Adverse perinatal outcomes are generally more frequent among RPL patients, but reports concerning the association between maternal p-MBL levels and perinatal outcomes, including birth weight (BW) and gestational age (GA), are conflicting. STUDY DESIGN, SIZE, DURATION This study was a combined cross-sectional and cohort study of 267 RPL patients admitted to the RPL Center of Western Denmark between January 2016 and March 2020. RPL patients were followed until birth of a liveborn child or until end of follow-up, March 2021. A sample of 185 healthy female blood donors of reproductive age was used as a MBL reference group. PARTICIPANTS/MATERIALS, SETTING, METHODS All RPL patients had ≥3 consecutive pregnancy losses, a regular menstrual cycle and no known significant chromosomal or uterine malformations. At the first consultation, routine blood samples including p-MBL measurement and detailed obstetrical and perinatal information were collected. p-MBL levels in RPL patients were compared to the MBL reference group. A logistic regression analysis adjusted for relevant confounders assessed the association between low p-MBL levels and an unsuccessful reproductive outcome in RPL patients in first pregnancy after admission. Perinatal outcomes before and after RPL were compared between RPL subgroups according to low (≤500 µg/l), intermediate (501–3000 µg/l) and high (>3000 µg/l) p-MBL levels. MAIN RESULTS AND THE ROLE OF CHANCE Significantly more RPL patients had low p-MBL levels (prevalence proportion ratio (PPR): 1.79, 95% CI: 1.34–2.38) and fewer had high p-MBL levels (PPR: 0.56, 95% CI: 0.40–0.79) compared to the reference group, while the prevalence of intermediate p-MBL level was not different between the groups (PPR: 0.86, 95% CI: 0.69–1.08). In the prospective study, low p-MBL level was not a significant risk factor for a pregnancy loss in the first pregnancy after admission after adjustment for age, BMI and smoking. Neither before nor after the RPL diagnosis were maternal p-MBL levels significantly associated with BW or GA. LIMITATIONS, REASONS FOR CAUTION Only 161 (60.3%) patients had given birth after RPL during the follow-up period, which limited the possibility to detect clear associations between p-MBL levels and perinatal outcomes after RPL. WIDER IMPLICATIONS OF THE FINDINGS In agreement with several previous studies, low p-MBL levels are strongly associated with RPL, while this study for the first time documents that high levels may play a protective role, which suggests a causal relationship. We suggest that larger prospective studies evaluate the association between p-MBL levels and RPL prognosis. STUDY FUNDING/COMPETING INTEREST(S) No external funding was received. We acknowledge the Department of Obstetrics and Gynaecology at Aalborg University Hospital for financial support. U.S.K. has reported personal fees from Merck, consulting fees from IBSA Nordic, and a grant from Gedeon Richter, Merck and IBSA Nordic outside of the submitted work. TRIAL REGISTRATION NUMBER ID from clinicaltrials.gov is NCT04017754. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the relationship between peritonitis attacks and mannose-binding lectin (MBL) gene polymorphism in patients undergoing peritoneal dialysis. Method: Codon 54 polymorphism found in exon 1 of the MBL gene was investigated by polymerase chain reaction-restriction fragment length polymorphism method in 45 patients with chronic renal failure undergoing peritoneal dialysis. Results: The frequency of the mutant B allele was not significantly higher in the patient group (4.4%) than the control group (2.1%). The AB genotype was found at a rate of 15.6% and 34% in the patient group and healthy control group, respectively. The AA genotype was found in 80% of children who underwent peritoneal dialysis and 63.8% of the healthy control group. Conclusion: In our study, no relationship was found between peritonitis attacks and MBL gene polymorphism in patients undergoing peritoneal dialysis.

Abstract Background The innate and adaptive immune system is involved in the airway inflammation associated with acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). We evaluated the association of mannose-binding lectin (MBL), immunoglobulin (Ig) and ficolin-2 concentrations with COPD exacerbations and according to the glucocorticoid treatment duration for an index exacerbation. Methods Post-hoc analysis of the randomized, double-blind, placebo-controlled REDUCE trial of 5 vs. 14 days of glucocorticoid treatment for an index exacerbation. MBL, ficolin-2 and total IgG/IgA and subclass concentrations were determined in stored samples drawn (n = 178) 30 days after the index exacerbation and associated with the risk of re-exacerbation during a 180-day follow-up period. Results IgG and subclass concentrations were significantly lower after 14 days vs. 5 days of glucocorticoid treatment. Patients with higher MBL concentrations were more likely to suffer from a future exacerbation (multivariable hazard ratio 1.03 per 200 ng/ml increase (95% confidence interval (CI) 1.00–1.06), p = 0.048), whereas ficolin-2 and IgG deficiency were not associated. The risk was most pronounced in patients with high MBL concentrations, IgG deficiency and 14 days of glucocorticoid treatment pointing towards an interactive effect of MBL and IgG deficiency in the presence of prolonged glucocorticoid treatment duration [Relative excess risk due to interaction 2.13 (95% CI − 0.41–4.66, p = 0.10)]. IgG concentrations were significantly lower in patients with frequent re-exacerbations (IgG, 7.81 g/L vs. 9.53 g/L, p = 0.03). Conclusions MBL modified the short-term exacerbation risk after a recent acute exacerbation of COPD, particularly in the setting of concurrent IgG deficiency and recent prolonged systemic glucocorticoid treatment. Ficolin-2 did not emerge as a predictor of a future exacerbation risk.

Objective: Previously, we have shown that predicted zymogen granule protein 16 homolog B (P-G3MZ19) existed in Bali cattle (Bos javanicus) saliva. It was suggested that P-G3MZ19 is a mem¬ber of the mannose-binding lectin family that plays an essential role in innate immunity. In the present study, we aimed to analyze the structure and ligand-binding of P-3MZ19 in Bali cattle saliva. Materials and Methods: Saliva of four adult healthy Bali cattle was collected, lyophilized, and subjected to two-dimensional (2-D) gel electrophoresis. The target spot of around 17 kDa related to P-G3MZ19 was excised for matrix-assisted laser desorption ionization time-of-flight mass spec¬trometer/time-of-flight mass spectrometer mass spectrometry analysis and sequencing. The structure and the ligand-binding of P-3MZ19 were analyzed using bioinformatics software pro¬grams published elsewhere. Results: Based on Iterative Threading ASSEmbly Refinement the 3D model of P-G3MZ19 was suggested to have similarities to exo-alpha-sialidase (EC 3.2.1.18); while its ligand-binding sites consisted of seven residues, i.e., 25aa-26aa (Gly-Gly), 95aa (Phe), 138aa (Tyr), 140aa (Leu), 141aa (Gly), and 143aa (Thr). Conclusion: The structure of P-G3MZ19 of Bali cattle saliva and its ligand-binding sites have been successfully determined by using bioinformatics techniques. The biological and immunological roles of the peptide are currently under investigation based on P-G3MZ19 synthetic peptides. [J Adv Vet Anim Res 2021; 8(2.000): 224-229]