"MBL deficiency"

Substitution of Mannan-Binding Lectin (MBL)-Deficient Serum With Recombinant MBL Results in the Formation of New MBL/MBL-Associated Serine Protease Complexes The lectin pathway (LP) of complement activation depends on the activation of the MBL-associated serine proteases (MASPs) circulating in complex with mannan-binding lectin (MBL). MBL deficiency is the most common complement deficiency chromatography for complexes of LP activation. In both sera, we identified non-bound free forms of MASP-2 and to lesser extent MASP-1/3. After addition of recombinant MBL (rMBL) to MBL-deficient serum, these free MASPs were much less abundantly present, which is highly suggestive for the formation of high-molecular complexes that could still become activated upon subsequent ligand binding as shown

Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL

, although all levels were still within the normal range; other studies have not supported the link with serum zinc levels. 29, 31 Mannose binding lectin (MBL) deficiency is a genetic condition that affects the immune system. Several studies have shown that MBL codon 54 gene polymorphism is associated with recurrent and acute VVC. In particular, possessing the MBL variant allele B heterozygous genotype , random blood glucose or HbA1c (Grade 2C) • iron-deficiency anaemia with a full blood count or serum ferritin (Grade 2C) Screening for mannose binding lectin deficiency can be considered if there are additional clinical indicators (e.g. history of recurrent upper respiratory tract infections or otitis media, autoimmune conditions). 82 (Grade 2B). Identifying MBL deficiency may help a patient

a possible link betweeniron deficiency anaemia and recurrent VVC.30The ear-lier study reported statistically significant lower serumlevel of zinc, magnesium and calcium in patients withrecurrent VVC, although all levels were still within thenormal range; other studies have not supported the linkwith serum zinc levels.29,31Mannose binding lectin (MBL) deficiency is a genet-ic condition that affects in patients presenting with acute VVC unlessclinically indicated. In recurrent VVC, screening for thefollowing conditions may be considered particularly ifthere are additional indicators:•diabetes with urinalysis, random blood glucose orHbA1c (Grade 2C)•iron-deficiency anaemia with a full blood count orserum ferritin (Grade 2C)Screening for MBL deficiency can be considered ifthere are additional clinical

.  No consensus on the clinical relevance of MBL deficiency.  The majority of individuals with low MBL levels are asymptomatic.  However, increased susceptibility to infection with MBL deficiency appears to occur when there are other concomitant factors impairing the immune system. Deficiencies in common final pathway • Major feature in this group is recurrent infections. • Generates membrane attack complex

by infection. MBL deficiency is thought to be the most common. Uncontrolled or deranged complement activity can also cause disease by promoting inflammation. The complement system can be involved in the pathogenesis of autoimmune diseases.EpidemiologyComplement deficiencies are rare. However, they are poorly characterised clinically and have been difficult to detect, so there is likely to be significant autosomal recessive inheritance. Properdin deficiency may be inherited as an X-linked trait. MBL deficiency can be both autosomal dominant and recessive. Complement deficiencies can also be acquired - for example, post-infection.PresentationClassical pathway component deficiencies (C1, C4, C2)Individuals are prone to immune complex disease, commonly systemic lupus erythematosus (SLE). The reason

and MBL play an important role in innate immunity. MBL deficiency manifests as increased susceptibility to polysaccharide-encapsulated bacteria, with subsequent recurrent respiratory tract infections, abscesses, sepsis, and meningitis. C1qRP deficiency has not been described.C3a, C4a, and C5a (CD88) receptorsReceptors for C3a and C5a have been identified; whether a distinct receptor for C4a is present

pattern recognition molecule of the innate immune system, plays an essential role in the host defense against certain infections and also appears to be a major regulator of inflammation. In this study, we investigated the function of MBL on the course of experimental murine imiquimod (IMQ)-induced psoriasis. Our data showed that MBL-deficient (MBL ) mice exhibited attenuated skin damage characterized by greatly decreased erythema compared with wild-type control mice during the early stages of IMQ-induced psoriasis-like skin inflammation. The reduced skin inflammation in MBL mice was associated with the decreased infiltration of neutrophils. Furthermore, we have determined that MBL deficiency limited the chemokine CXCL1 production from skin keratinocytes upon IMQ stimulation, which might be responsible

Increased risk of group B Streptococcus causing meningitis in infants with mannose-binding lectin deficiency. To evaluate the association of mannose-binding lectin (MBL) deficiency with susceptibility and clinical features of group B Streptococcus (GBS) causing meningitis in Chinese infants. During 2014-2017, 33 infants with laboratory-confirmed GBS meningitis were included. Six polymorphisms (H of patients with different genotypes. Our result suggested that infants with MBL deficiency are at higher risk of meningitis caused by GBS. Further studies in different populations with larger number of subjects are needed.

by ischemia is a major pathogenic event leading to brain injury. The molecular mechanisms through which MBL influences outcome after ischemia are not understood yet. Approach and Results- Here we show that MBL-deficient (MBL) mice subjected to cerebral ischemia display better flow recovery and less plasma extravasation in the brain than wild-type mice, as assessed by in vivo 2-photon microscopy . This results in reduced vascular dysfunction as shown by the shift from a pro- to an anti-inflammatory vascular phenotype associated with MBL deficiency. We also show that platelets directly bind MBL and that platelets from MBL mice have reduced inflammatory phenotype as indicated by reduced IL-1α (interleukin-1α) content, as early as 6 hours after ischemia. Cultured human brain endothelial cells subjected

Autosomal dominant mannose-binding lectin deficiency is associated with worse neurodevelopmental outcomes after cardiac surgery in infants. The MBL2 gene is the major genetic determinant of mannose-binding lectin (MBL)-an acute phase reactant. Low MBL levels have been associated with adverse outcomes in preterm infants. The MBL2 missense variant causes autosomal dominant MBL deficiency. We developmental problem score (β = 3.98; P = .0025). Sensitivity analyses of the interaction between age at first surgery and MBL genotype suggested effect modification for the patients with MBL2 (P = .039), with the poorest neurodevelopment outcomes occurring in children who had surgery earlier in life. We report the novel finding that carriers of MBL2 causing autosomal dominant MBL deficiency have increased

CAP (8.48 vs 9.97 g/L, = .023), but low Igs were not associated with microbial etiology. Fifty-five (21%) patients had low lectin pathway activity, of which 33 (13%) were mannose-binding lectin (MBL) deficient. Low admission levels of any Ig or MBL were not associated with disease severity, short-term outcome, or long-term outcome. Excluding patients defined as immunocompromised from analysis did

also 1 and/or 3 months post transplantation. The results were compared with data from 267 healthy controls and analyzed in relation to clinical data to explore possible associations with cancer and with chemotherapy-induced medical complications. We found a higher frequency of MBL deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients compared with controls. It was however of MBL on infections following chemotherapy of myeloma and lymphoma have been reported. Here we found no evidence for an association between MBL deficiency and infection during the short period of neutropenia following conditioning treatment before HSCT. However, we noted a possible protective effect of MBL during follow-up, and suspected that to be fully effective when able to act in combination

whether MBL deficiency was more frequently present in cases group of tubotympanic CSOM patients rather than healthy subjects. This was an analytic observational study. Subjects were enrolled in the Otorhinolaryngology Clinic at Margono Soekarjo Hospital, Purwokerto, Indonesia. An independent -test was used to compare the mean of MBL serum concentration between tubotympanic CSOM subjects and control . From 36 tubotympanic CSOM patients, there were 8 (22.22%) patients with MBL deficiency (MBL level < 100 ng/ml), while no deficiency was found in the control group. The mean of MBL level in cases group was 354.88 ng/ml, with the lowest level being 0.001 ng/ml and the highest level 690.24 ng/ml, while in the control group MBL level mean was 376.27 with the lowest level being 188.71 and the highest

Serial Changes in Mannose-Binding Lectin in Patients with Sepsis Mannose-binding lectin (MBL) deficiency leads to increased susceptibility to infection. We investigated whether serial changes in MBL levels are associated with the prognosis of patients diagnosed with septic shock, and correlated with cytokine levels. We enrolled 131 patients with septic shock in the study. We analyzed the serum

Genetic mannose binding lectin deficiency is associated with airway microbiota diversity and reduced exacerbation frequency in COPD. In cystic fibrosis and bronchiectasis, genetic mannose binding lectin (MBL) deficiency is associated with increased exacerbations and earlier mortality; associations in COPD are less clear. Preclinical data suggest MBL interferes with phagocytosis of , a key COPD pathogen. We investigated whether MBL deficiency impacted on clinical outcomes or microbiota composition in COPD. Patients with COPD (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality. A nested subcohort of 141 patients, followed for up to 6 months, was studied to test if MBL deficiency was associated with altered sputum microbiota

Mannose-binding lectin deficient donors increase the risk of bacterial infection and bacterial infection-related mortality after liver transplantation. Mannose-binding lectin (MBL) is synthesized by the liver and binds to microbes. MBL2 gene polymorphisms produce intermediate/low/null or normal MBL serum levels (MBL-deficient or MBL-sufficient phenotypes, respectively). We aimed to evaluate viral non-CMV-related episodes) and 48 rejection episodes were recorded. The main bacterial infections were urinary (n = 82, 26%) and pneumonia (n = 69, 22%). LT recipients of MBL-deficient livers had a higher risk of bacterial infection (incidence rate ratio [IRR] 1.48 [95% confidence interval 1.04-2.09], p = 0.028), pneumonia (IRR 2.4 [95% confidence interval 1.33-4.33], p = 0.013), and septic shock

and 489 healthy controls. Overall, 5.2% (39 of 749) of patients with IgAN had MBL deficiency (MBL levels <100 ng/ml), among whom LYPB/LYPB and LXPA/LYPB were the predominant haplotypes (82%; 32 of 39). We found a nonlinear association between MBL levels and renal outcome in IgAN. Patients with IgAN and MBL deficiency had a higher incidence of prodromic infections and gross hematuria than those with sufficient MBL levels (100-3540 ng/ml). Moreover, MBL deficiency independently associated with poor renal outcome in IgAN after multiple adjustments (hazard ratio, 5.18; 95% confidence interval, 2.50 to 10.72; <0.001). Patients with high MBL levels (>3540 ng/ml) had more severe proteinuria and a higher proportion of crescents, although the association with IgAN progression did not reach statistical

two (P/Q and A/B) within exon 1. MBL concentrations in the blood were estimated by ELISA. The prevalence of haplotype HYPB, leading to MBL deficiency, was significantly decreased in the AD patients compared to the controls (=0.002), while the prevalence of haplotype HYPA was increased with a clear trend toward significance (=0.056). The frequency of LYPB/LXPA (odds ratio, 0.08; 95% confidence