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Background: 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. Aim of the work: 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. Patients and methods: 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. Results: 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

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 &lt, 18-years-old and included 43 patients with bronchial asthma and 64 age-matched healthy subjects as a control group. We used the ELISA Human MBL Immunoassay kit and the electrochemiluminescence immunoassay (ECLIA) kit for IgE determination. 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.

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.

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.

Background: Mannose binding lectin (MBL) appears to be involved in susceptibility to rheumatoid arthritis (RA), in the inflammatory process and in the genesis of atherosclerotic disease. Objective: To study the association of MBL serum levels and its genotypic variation with carotid arteries intimal thickness (IMT) in RA patients from Southern Brazil. Methods: MBL serum levels, MBL2 genotyping and IMT were investigated in 90 RA patients along with their demographic, clinical and laboratory profile. MBL levels and MBL2 genotyping were evaluated in 90 healthy controls. Results: A significant lower MBL serum concentration was observed in patients with RA in relation to controls (528 ng/mL vs 937.5 ng/mL, p = 0.05, respectively). The median IMT in RA patients was 0.59 mm (0.51 to 0.85 mm). There was no correlation between levels of MBL with disease activity, erythrocyte sedimentation rate, autoantibodies presence or IMT (p = NS). A weak and negative correlation was found between MBL and CRP levels (Rho = −0.24; p = 0.02;). The MBL2 variant at codon 54 (variant B) and HYPA haplotype were the most frequently observed in the RA sample (67.5% and 31.7%). MBL2 wild type (A/A) were associated with lower IMT when compared with heterozygotes (A/O; p = 0.04) and low producers (O/O; p = 0.05). In addition, high producers genotypes had lower levels of CRP when compared with medium (p = 0.04) or with low producers (p = 0.05). Conclusion: RA patients had lower MBL levels than controls. MBL were negatively associated with CRP serum levels; low MBL genotypes producers increased thickness of the IMT than high producers. Keywords: Mannose binding lectin, Rheumatoid arthritis, Atherosclerosis

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.

Resumen Objetivos: 1) Identificar las variables que se asocian con los niveles urinarios de MBL, C4d y C5b-9 en enfermos con nefropatía IgA idiopática. 2) Analizar si los niveles urinarios de MBL o C4d son útiles para identificar la presencia de depósitos mesangiales de C4d/MBL. Pacientes y método: Se estudió a 96 enfermos con nefropatía IgA primaria. Se registraron las variables demográficas, clínicas y bioquímicas en el momento del diagnóstico. Las lesiones renales se cuantificaron mediante la clasificación de Oxford. En las biopsias, se realizaron tinciones inmunohistoquímicas para MBL, properdina, C4d, y C5b-9. En orina, se determinó el nivel de properdina, MBL, C4d y C5b-9. Resultados: Los predictores independientes de los niveles de C4d y MBL en orina fueron el depósito mesangial de cada una de ellas y, en menor grado, la proteinuria. Los predictores independientes de los niveles urinarios de C5b-9 fueron los niveles de MBL y properdina, y la proteinuria. La excreción urinaria de C4d tuvo una sensibilidad del 90% (IC 95%: 58,7-99) y una especificidad del 73% (IC 95%: 54-87) para la detección de depósitos mesangiales de C4d y el nivel de MBL tuvo una sensibilidad del 83,9% (IC 95%: 62-95) y una especificidad del 81,6% (IC 95%: 65-92) para identificar depósitos mesangiales de MBL. Conclusión: El principal predictor de la concentración urinaria de C4d y MBL es la presencia de depósitos mesangiales de ellas. La MBL podría contribuir a la activación del complemento en la luz tubular a través de la vía de las lectinas. Los niveles urinarios de MBL y C4d podrían ser biomarcadores sensibles y específicos para la identificación de los enfermos que presentan depósitos mesangiales de MBL o C4d. Abstract 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 to 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.

Summary Community‐acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose‐binding lectin (MBL) and l‐ficolin (l‐FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Chlamydia species or Mycoplasma pneumoniae) compared with controls (P = 0·016). Furthermore, patients with these haplotypes were more often bacteraemic (P = 0·019). It can therefore be concluded that MBL2 and FCN2 polymorphisms are not major risk factors for CAP in general, but that the +6424G>T SNP in the FCN2 gene predisposes to C. burnetii pneumonia. In addition, patients with genotypes corresponding with high serum MBL levels are at risk for atypical pneumonia, possibly caused by enhanced phagocytosis, thereby promoting cell entry of these intracellular bacteria.

Aim of the work The present study was undertaken to determine whether mannose binding lectin-2 (MBL2) promotor-221X/Y gene polymorphism had a possible association with systemic lupus erythematosus (SLE) in Mansoura city. Patients and methods We analyzed functional polymorphisms in the promoter of MBL2 gene in 106 Egyptian SLE patients and 99 healthy controls by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). SLE disease activity was evaluated using SLE Disease Activity Index (SLEDAI) and organ damage was evaluated using SLE International Collaborating Clinic Damage Index (SLICC/DI). Results The patients were 95 females and 11 males with a mean age of 34.4 ± 10.2 years and disease duration of 4 ± 3.03 years. Genotype frequencies of MBL2 were significantly different between patients and controls. The YY genotype was significantly associated with SLE in 77 (72.6%) patients compared to the control in 59 (59.6%) ( p = 0.048). The XY genotype was in 29 (27.4%) patients and in 40 (40.4%) control. An association was found between the XY genotype and alopecia ( p = 0.048), central nervous system involvement ( p = 0.03), vasculitis ( p = 0.004) and anti-phospholipid syndrome ( p = 0.001) while the YY genotype was associated with discoid rash, low serum complement level (C3; p = 0.014 and C4; p = 0.008) and with the presence of anticardiolipin antibodies ( p = 0.032). MBL genotype did not show any correlation with SLEDAI or SLICC/DI. Conclusion Our results indicate that MBL2 promotor-221X/Y polymorphism is a possible key-player for SLE development as well as the occurrence of some clinical and laboratory features. Further longitudinal studies including other single nucleoproteins are needed to clarify the role of MBL2.

Mannose-binding lectin (MBL) is a circulating protein that acts as a soluble pattern recognition molecule of the innate immunity. It binds to carbohydrate patterns on the surface of pathogens or of altered self-cells, with activation of the lectin pathway of the complement system. Recent evidence indicates that MBL contributes to the pathophysiology of ischemia-reperfusion injury and other conditions. Thus, MBL inhibitors offer promising therapeutic strategies, since they prevent the interaction of MBL with its target sugar arrays. We developed and characterized a novel assay based on surface plasmon resonance for in vitro screening of these compounds, which may be useful before the more expensive and time-consuming in vivo studies. The assay measures the inhibitor's ability to interfere with the binding of murine MBL-A or MBL-C, or of human recombinant MBL, to mannose residues immobilized on the sensor chip surface. We have applied the assay to measure the IC50 of synthetic glycodendrimers, two of them with neuroprotective properties in animal models of MBL-mediated injuries.

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., Highlights • The FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections. • The FcMBL ELLecSA distinguished infection from trauma-related inflammation. • It can detect infection even when blood cultures are negative and antibiotic therapy has been initiated. Current diagnostics of sepsis using blood cultures and molecular diagnostic tests fail to detect bloodstream infections in most infected patients, whereas the inflammatory biomarkers of infection that have a higher sensitivity of detection, lack specificity in distinguishing infection from trauma-related inflammation. Therefore we have leveraged a broad-spectrum pathogen binding opsonin and developed a rapid test to directly diagnose the presence of infection in the blood to triage patients and guide antibiotic therapy.

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.

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.

Mannose binding lectin (MBL) is a collagenous C-type lectin, which plays an important role in innate immunity. It can bind to carbohydrates on the surface of a wide range of pathogens, including viruses. Here we studied the antiviral effect of recombinant chicken (rc)MBL against Infectious Bronchitis Virus (IBV), a highly contagious coronavirus of chicken. rcMBL inhibited in a dose-dependent manner the infection of BHK-21 cells by IBV-Beaudette, as detected by immunofluorescence staining of viral proteins and qPCR. ELISA and negative staining electron microscopy showed that rcMBL bound directly to IBV, resulting in the aggregation of viral particles. Furthermore, we demonstrated that MBL bound specifically to the spike S1 protein of IBV which mediates viral attachment. This subsequently blocked the attachment of S1 to IBV-susceptible cells in chicken tracheal tissues as shown in protein histochemistry. Taken together, rcMBL exhibits antiviral activity against IBV, based on a direct interaction with IBV virions., Highlights • Recombinant chicken MBL (rcMBL) has antiviral activity against IBV-Beaudette in cell culture. • rcMBL aggregates IBV virus-particles. • rcMBL binds through its carbohydrate recognition domain to the S1 spike protein of IBV. • rcMBL can prevent binding of IBV-S1 to chicken tracheal tissues.

Elderly with late-onset recurrent respiratory tract infections (RRTI) often have specific anti-polysaccharide antibody deficiency (SPAD). We hypothesized that late-onset RRTI is caused by mild immunodeficiencies, such as SPAD, that remain hidden through adult life. We analyzed seventeen elderly RRTI patients and matched controls. We determined lymphocyte subsets, expression of BAFF receptors, serum immunoglobulins, complement pathways, Pneumovax-23 vaccination response and genetic variations in BAFFR and MBL2. Twelve patients (71%) and ten controls (59%) had SPAD. IgA was lower in patients than in controls, but other parameters did not differ. However, a high percentage of both patients (53%) and controls (65%) were MBL deficient, much more than in the general population. Often, MBL2 secretor genotypes did not match functional deficiency, suggesting that functional MBL deficiency can be an acquired condition. In conclusion, we found SPAD and MBL deficiency in many elderly, and conjecture that at least the latter arises with age.

Background Circulating bone marrow-derived monocytes can leave the blood, enter a tissue, and differentiate into M1 inflammatory, M2a remodeling/fibrotic, or M2c/Mreg resolving/immune-regulatory macrophages. Macrophages can also convert from one of the above types to another. Pentraxins are secreted proteins that bind to, and promote efficient clearance of, microbial pathogens and cellular debris during infection, inflammation, and tissue damage. The pentraxins C-reactive protein (CRP), serum amyloid P (SAP), and pentraxin-3 (PTX3) can also bind a variety of endogenous ligands. As monocytes and macrophages are exposed to differing concentrations of pentraxins and their ligands during infection, inflammation, and tissue damage, we assessed what effect pentraxins and their ligands have on these cells. Results We found that many polarization markers do not discriminate between the effects of pentraxins and their ligands on macrophages. However, pentraxins, their ligands, and cytokines differentially regulate the expression of the hemoglobin-haptoglobin complex receptor CD163, the sialic acid-binding lectin CD169, and the macrophage mannose receptor CD206. CRP, a pentraxin generally thought of as being pro-inflammatory, increases the extracellular accumulation of the anti-inflammatory cytokine IL-10, and this effect is attenuated by GM-CSF, mannose-binding lectin, and factor H. Conclusions These results suggest that the presence of pentraxins and their ligands regulate macrophage differentiation in the blood and tissues, and that CRP may be a potent inducer of the anti-inflammatory cytokine IL-10. Electronic supplementary material The online version of this article (doi:10.1186/s12865-017-0214-z) contains supplementary material, which is available to authorized users.

[Abstract] 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. Instituto de Salud Carlos III; PI13/02174

Amac: Kompleman aktivasyonunun lektin yolaginda rol oynayan ve dogal immun sistemin bir parcasi olan mannoz baglayici lektin (MBL), cesitli patojenlerin mannan gruplarinin uyarisi ile aktive olur. MBL genindeki bazi polimorfizmler (orn. kodon 52, kodon 54 polimorfizmleri) MBL’nin serum duzeylerinde degisikliklere yol acarak, infeksiyon hastaliklarina yatkinliga neden olabildigi gibi, bazi otoimmun ve inflamatuvar hastaliklarin patogenezine de katkida bulunabilir. Bu calismada, ailesel Akdeniz atesi (AAA) hastalarinda MBL geni kodon 52 ve kodon 54 polimorfizmlerinin sikligini ve basta sekonder amiloidoz olmak uzere, hastaligin klinik ozellikleri ile olasi iliskilerini arastirmayi amacladik. Gerec ve Yontem: Yuzelli-yedi AAA hastasinda ve hastalarla akrabalik iliskisi olmayan benzer demografik dagilimdaki 150 saglikli kontrolde MBL genindeki R52C C>T ve G54D G>A polimorfizmleri sekanslama yontemi ile arastirildi. AAA hastalarinin MEFV geni analizleri, klinik ozellikleri ve ataksiz donemdeki serum CRP duzeyleri kaydedildi. Genetik sonuclar ile klinik ve laboratuvar bulgular arasindaki olasi iliskiler incelendi. Bulgular: MBL geni R52C C>T polimorfizmi hastalarin %12,7’sinde, kontrol grubunun %10,6’sinda saptandi. G54D G>A polimorfizmi hastalarin %26,8’sinde, kontrollerin %26,7’sinde saptandi. Polimorfizm sikligi acisindan, iki grup arasinda anlamli fark bulunamadi (p=0,79 ve 0,98). Incelenen MBL geni polimorfizmleri ile hastalarin cesitli klinik ozellikleri (or. amiloidoz, ates, kolsisin yaniti, MEFV mutasyonlari) arasinda anlamli iliski bulunamadi. AAA hastalarinin ortalama CRP degeri 4,90±6,72 mg/dL olup, ataksiz donemde serum CRP duzeyi normalden yuksek (>0,8 mg/dL) olan hastalarda MBL kodon 52 polimorfizmi sikligi %25,2, kodon 54 polimorfizmi sikligi %14,8 oraninda bulundu. AAA hastalarinda yuksek CRP duzeyine gore kodon 52 ve kodon 54 polimorfizmi sikliklari farkli bulunmadi (p=0,399). AAA hastalarinda M694V mutasyonu ile amiloidoz arasinda (p=0,002) ve M694I mutasyonu ile kolsisin direnci arasinda (p=0,016) anlamli iliski saptandi. Sonuc: AAA hastalarin ataksiz donemdeki CRP duzeyleri ve tasidiklari klinik ozellikler ile MBL polimorfizmleri arasinda anlamli iliski bulunamamasi, AAA hastalarinin proinflamatuvar durumda oldugunu ve MBL aracili mekanizmalarin bu sureclere katkisinin olmadigini dusundurmektedir. Olgularimizda M694I ile kolsisin direnci arasinda anlamli iliski saptanmis olmasi dikkate deger bir bulgudur. Yine olgularimizda M694V ile amiloidoz arasinda anlamli iliski bulunmasi onceki literatur bulgulari ile uyumludur ve M694V’nin hastalik siddeti ve prognozu icin onemli oldugu gorusunu desteklemektedir.

Background: Lectin pathway mediates complement activation, which is activated by many microorganisms. This study aimed at determining the serum levels of mannose-binding lectin (MBL) in patients with pulmonary tuberculosis, assessing its relationship to antiuberculosis treatment response, and comparing them with a control group. Methods: This cross-sectional study was conducted on patients with pulmonary tuberculosis during 2012 and 2013 in South West of Iran. PPD-ST-negative individuals were selected as controls from healthy relatives of patients. Serum MBL levels were measured using ELISA kit (Human MBL HK323, Hycultbiotech Company, Netherlands). All patients were followed- up for response to treatment. We applied Mann-Whitney and Fisher’s exact tests and used SPSS Version 17 software for statistical analysis. Results: The study included 62 patients as the case group and 63 noninfected TB patients as the control group. The MBL (ng/mL) in patients with pulmonary tuberculosis (median = 1012) was significantly (p= 0.037) higher than that of the control group (median= 296.2). No significant difference was found in the MBL level (ng/mL) between patients with response to antituberculosis treatment (median= 1012) and patients with treatment failure (median= 798.9) (p= 0.84). Conclusion: MBL may be involved in the pathogenesis of tuberculosis and in the low values that are protective against tuberculosis, and it seems that it has no effect on the antituberculosis treatment response.

This case report describes a 5-year-old boy who presented to the emergency department with clinical symptoms and chest X-ray findings suggestive of pneumonia. Further history revealed multiple other infections, and workup for immunodeficiency revealed a deficiency of mannose-binding lectin (MBL), a pattern recognition receptor involved in activation of the complement system. Innate immunodeficiency may be more common than currently appreciated, with mutations of MBL affecting up to 50% of individuals in some populations. While pneumonia is a common presentation in the Pediatric Emergency Department, clinical presentations of children with defects of innate immunity can be unpredictable. Children may initially appear well with sudden deterioration. These cases pose particular challenges to physicians, and the level of suspicion for innate defects must remain high. It is crucial to identify patients with such impairments to better manage and prevent future complications.

Myocardial inflammation is one of the commonest mechanisms in cardiomyopathy (CMP). Mannose binding lectin (MBL) is a key molecule in innate immunity, while macrophage migration inhibitory factor (MIF) is a constitutive element of the host defenses. We investigated the possible association between polymorphisms of MBL2 and MIF genes and CMP in Turkish children. Twenty-children with CMP and 30 healthy controls were analyzed for codon 54 A/B polymorphism in MBL, and -173 G/C polymorphism in MIF genes by using PCR-RFLP methods. No significant difference was found between genotypes and alleles of MBL2 gene codon 54 A/B polymorphism in patients and controls (p>0.05). However, serum uric acid levels was found higher in dilated CMP patients with AA genotype. Frequency of MIF -173 CC genotype was significantly higher in patients (p

Objective: Mannose binding lectin (MBL) is one of the three initiators of complement activation. Polymorphisms of the MBL2 gene and its promoter, and especially haplotypes, determine MBL plasma levels. MBL deficiency has been associated with the development of atherosclerosis. We evaluated whether the rate of angiographic progression of coronary atherosclerosis during pravastatin treatment was associated with MBL2 haplotypes in REGRESS, a placebo-controlled 2 years intervention study. Methods: Three polymorphic sites in exon 1 (rs1800450, rs1800451 and rs5030737) of the MBL2 gene and 2 sites (rs7096206 and rs11003125) in the promoter region were genotyped in 398 subjects. Genotyping was performed using Applied Biosystems (R) TaqMan (R) Genotyping Assays. We divided the group in high, intermediate and low MBL2 secretor haplotypes. Quantitative coronary angiography was performed. Endpoints were mean segment diameter (MSD) and minimum obstruction diameter (MOD) established by quantitative coronary angiography. Results: At inclusion, 50.1, 31.7 and 17.6% of the patients in the REGRESS cohort carried the high, intermediate and low MBL2 secretor haplotypes, respectively. In 0.6% of the patients, the haplotype was not informative. There were no baseline differences between the MBL2 haplotypes for age, BMI, lipid levels, leukocyte counts, CRP, MSD and MOD. The intermediate MBL2 placebo group showed the greatest increase in MSD compared to the low MBL2 group (P = 0.03). No difference was found for the change in MOD. No significant interaction between MBL2 haplotype groups and pravastatin therapy was observed. Conclusion: In men with proven coronary artery disease, MBL2 secretor haplotypes are not associated to the rate of progression of coronary sclerosis nor does pravastatin treatment influence progression based on MBL2 haplotypes. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Background. Lung transplantation is a well accepted therapy for end-stage lung disease, despite high mortality rates. Mortality after transplantation is mainly caused by allograft failure in the first years after transplantation. Mannose binding lectin (MBL), a recognition molecule of innate immunity, his been associated with transplant Outcome in other solid organ transplantation. In this study, the effect of donor- and recipient-MBL genotype on lung transplant Outcome was investigated.Materials and Methods. All lung transplantations performed in our center, except from retransplantations and combined king-liver or heart-lung transplantations, were included, Genotyping of the MBL2 variants (promoter: L/H, Y/X, and P/Q allele and exon 1: A/D, A/B, and A/C allele) was performed in donor and recipient DNA. Analyses on graft survival and the development of bronchiolitis obliterans syndrome were performed with Kaplan-Meier (log rank) survival analysis.Results. Of the 277 included cases, DNA was available from 189 donors and 200 recipients and genotyping of the promoter single nucleotide polymorphisms was successful in 184 donors and 198 recipients and of the exon 1 single nucleotide polymorphisms in 181 donors and 193 recipients. Patients who received a graft from a donor with an X-allele had better graft survival (P=0.007) and bronchiolitis obliterans syndrome free survival (P=0.007). Recipient MBL genotype was not associated with transplant outcome.Conclusion. The donor X-allele, which corresponds to the LXPA haplotype is associated with superior lung transplant Outcome. Our findings might prove to be important in finding ways to optimize Outcome after lung transplantation.

There have been a number of recent advances in the genetic understanding of photosensitive rheumatic diseases, especially subacute cutaneous lupus erythematosus and dermatomyositis. These advances support the concept that increased numbers of ultraviolet light-induced apoptotic cells in skin lead to a supra-threshold concentration of antigenic peptides. The current genetic data suggest that increased keratinocyte apopotosis can result from increased amounts of TNF-alpha that induce apoptosis due to a ultraviolet light-sensitive TNF promoter polymorphism or to decreased clearance of apototic cells due to polymorphisms associated with decreased serum levels of collectins such as C1q and mannose-binding lectin. These diseases are frequently oligogenic, and other yet to be elucidated genes will, in individual patients, lead to increased numbers of apoptotic cells associated with these cutaneous autoimmune diseases. In the presence of specific MHC class I and II genes, antigen-presenting cells initiate a primary immune response that leads to cutaneous, and likely systemic, autoimmune disease.

WOS: 000333391800014, PubMed ID: 24576294, AimImmune and inflammatory response activation is a common feature of systemic vasculitis. There is a protein called mannose binding lectin (MBL) that was reported to play an important role in innate immunity. MBL polymorphisms in the MBL gene cause predisposition to infectious and autoimmune diseases. There is no study in the literature investigating the association between MBL polymorphisms and Henoch-Schonlein purpura (HSP) to date. Therefore, the aim of this study is to determine the presence of any association between MBL gene variants and HSP in a child population. MethodCodon 54 polymorphism in exon 1 of the MBL gene was investigated by polymerase chain reaction - restriction fragment length polymorphism method in 100 children diagnosed as having HSP and 100 age-matched healthy controls. ResultsThe mutant B allele frequency was not significantly higher in the patient group (16%) compared to the control group (14%). AB genotype was found to be 28% and 26% in the patient group and healthy control group, respectively. AA genotype was found in 70% of the children with HSP and 73% of the healthy control group. ConclusionThese results suggest that codon 54 polymorphism in the MBL gene may hardly play a role in susceptibility to HSP in children, the first time this has been reported in the literature.

Background Long-term lung allograft survival is limited by bronchiolitis obliterans syndrome (BOS). Mannose binding lectin (MBL) belongs to the innate immune system, participates in complement activation, and may predispose to graft rejection. We investigated mannose binding (MBL) during cold ischemia and in tissue samples from explanted lungs with BOS, and assessed MBL and complement proteins in plasma post-lung transplantation relative to BOS staging. Methods MBL was detected by immunohistochemistry lung tissue at the time of cold ischemia and in samples with BOS. MBL was assayed in the peripheral blood of 66 lung transplant patients transplanted between 1990–2007. Results MBL localized to vasculature and basement membrane during cold ischemia and BOS. Patients further out post-lung transplant > 5 years (n = 33), had significantly lower levels of MBL in the blood compared to lung transplant patients Conclusions MBL localizes within the lung during graft ischemia and BOS, higher levels of plasma MBL are associated with BOS Op-3 and

This study examined efficacy of the innate immune defence via the mannose binding lectin (MBL) in a cohort of 55 dystonic patients prospectively referred to the clinic with laryngeal mucosal complaints, who were placed on local steroids (budesonid inhaler, 400 μg 2 times daily) and antihistamines (fexofenadin 180 mg mostly 3 times daily) with adjuvant lifestyle corrections. Treatment efficacy of the larynx was assessed based on mucosal findings of the vocal folds examined with phonatory function studies (PhFS) comprising simultaneous high-speed digital images, kymography, electroglottography and voice acoustics combined with a visual score of arytenoids oedema, as these measures are indicative of the magnitude of laryngitis. Lactose and gluten intolerance and immunological analyses of the innate system were made systematically. Results showed that the genetic aspects of immunology did not reveal a role for the innate immune system, represented by the MBL. But an unexpected positive effect of the larynx treatment on dystonia symptoms was found evidenced by reduction of dystonic complaints and more normative results of PhFS, and a reduction of oedema of the inter arytenoids region. Symptoms relieve and better quality of life was observed on follow-up for the dystonia complaints.

Objective: The aim of this study was to determine the serum mannose-binding lectin (MBL) levels and the frequency of MBL gene polymorphisms in infants with neonatal sepsis. Study Design: Between January 2008 and January 2010, a total of 93 infants were included in this study and 53 of them had neonatal sepsis diagnosis as study group and 40 infants who had no sepsis according to clinical and laboratory findings as control group. Result: Serum MBL levels were found to be low in 17 of 93 infants. Eleven of them were in the sepsis group and six of them were in the control group. Serum MBL levels were significantly lower in infants with sepsis compared with the control group. Frequencies of genotype AB and BB were also significantly higher in the study group compared with the control group. Most importantly, presence of B allele of MBL exon 1 gene was found to be associated with an increased risk for neonatal sepsis. Additionally, in the study group, the mean serum MBL levels were found to be significantly lower in the premature infants compared with the term infants. Pneumonia, bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH) were significantly higher in infants with MBL deficiency compared with infants with normal MBL levels. Conclusion: Low MBL levels and presence of B allele of MBL exon 1 gene were found to be important risk factors for development of both neonatal sepsis and pneumonia, especially in premature infants. Low MBL levels and MBL gene polymorphisms might also be associated with inflammation-related neonatal morbidities such as BPD and IVH.

El-Omar et al. (1) reported that interleukin (IL)-1 gene cluster variants that enhance the production of IL-1β (a powerful inhibitor of gastric acid secretion) increase the risk of gastric cancer in Helicobacter pylori (HP)-infected patients. IL-1β production is down-regulated by mannose-binding lectin (MBL) (2), an acute-phase glycoprotein that has a high affinity for gram-negative lipopolysaccharide and exerts immunological activity (3)(4). Variants in the promoter, the 5′UTR, and exon 1 of the MBL2 gene reduce the synthesis and activity of MBL (5). To assess the relationships between MBL2 gene variants and HP-related gastric cancer, we analyzed the whole coding region and the 5′UTR of the MBL2 gene in DNA extracted (QIAamp, Qiagen) from neoplastic cells embedded in paraffin sections (used for histological diagnosis) from 145 unrelated patients (90 males) affected by noncardia gastric cancer. Eighty-seven (60.0%) had intestinal-type; 47 (32.4%), diffuse-type; and 11 (7.6%), mixed-type adenocarcinoma. All patients had HP-positive serology. For 75 patients, we …

Celiac disease is a multifactorial disorder caused, in genetically susceptible patients, by the ingestion of dietary gluten. Very little is known about the genetic factors, but there is a strong association of two HLA haplotypes (DQ2 or alpha1*05, beta1*02 and DQ8 or alpha1*0301, beta1*0302) with the disease. We investigated the relationship between polymorphisms in the first exon of the MBL2 gene, which encodes for mannose binding lectin (MBL) and celiac disease. Moreover we studied the MBL role by immunohistochemistry and TUNEL. Results were confirmed by clinical findings. We enrolled 149 Italian celiac patients; 116 were characterized by the presence of DQ2 or DQ8. The HLA haplotype was established by allelic specific PCR while the MBL2 genotype was resolved by melting temperature assay. Immunohistochemistry and TUNEL assays were performed on serial sections of biopsy specimens from celiac patients and healthy controls. MBL2 allele and genotype frequencies varied significantly between celiac patients and healthy controls. The frequencies of the 0 allele were 28% in DQ2 or DQ8 celiac patients, 36% in HLA atypical celiac patients, and 22% in healthy controls. Interestingly, the MBL2 0/0 genotype was present in 7 of 33 HLA atypical celiac patients (21%) and in 13 of 116 HLA typical celiac patients (13%) but in only 7 of 147 healthy controls (5%). Furthermore, we found that MBL2 genotype is strongly associated with the occurrence of secondary autoimmune diseases. Immunohistochemistry and TUNEL findings support a role of MBL2 in the clearance of apoptotic cells. In conclusion, MBL2 variants, responsible for lower MBL levels, are associated with celiac disease and higher risk of developing autoimmune diseases. Here we propose a role for MBL in the disease which could be easily applied to other autoimmune disorders.

Background Altered plasma concentrations of vitamin D and mannose binding lectin (MBL), components of innate immunity, have been shown to be associated with the pathogenesis of viral infections. The objective of the present study was to find out whether plasma concentrations of MBL and vitamin D are different in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). The results The plasma concentrations of vitamin D and MBL were assessed in 48 DF cases, 45 DHF cases and 20 apparently healthy controls using ELISA based methods. Vitamin D concentrations were found to be higher among both DF and DHF cases as compared to healthy controls (P P P P P = 0.038). Conclusions The present study suggests that higher concentrations of vitamin D might be associated with secondary DHF while deficiency of MBL may be associated with primary DHF.