Lectin Levels Research Articles

SNPs in 3′-UTR region of MBL2 increases susceptibility to recurrent vulvovaginal infections by altering sMBL levels

Recurrent vulvovaginal infections (RVVI), owing to their adverse health consequences, have become a serious dilemma worldwide. Low serum levels of Mannose-Binding Lectin (sMBL), a main component of innate immunity, was found to be associated with RVVI risk, though complete genetic bases are still elusive. To reveal unrecognised regulatory variants, 3′-UTR region of MBL2 with six putative functional SNPs i.e. rs10824792, rs2120132, rs2120131, rs2165813, rs2099903 and rs2099902 was sequenced and genotyped in the present study for 109 RVVI cases and age matched healthy controls. sMBL levels were measured by enzyme-linked immunosorbent assay. The homozygous CC genotype of rs10824792 polymorphism was found to be conferring risk (OR = 2.94) of developing RVVI. Significantly high frequency of corresponding CC genotype was found in Vulvovaginal Candidiasis (VVC) and Mixed Infections (MI) relative to controls. Significantly insufficient sMBL levels were observed in RVVI and its types (Bacterial Vaginosis, VVC and MI) than controls. sMBL levels varied for rs10824792 SNP as expected from the genetic analyses. Six marker haplotype analyses have shown CTTGCT, the haplotype containing only risk allele of rs10824792, conferred risk of RVVI and its types by lowering sMBL levels. In conclusion, a 3′-UTR SNP i.e. rs10824792 was identified as novel associated genetic marker for contributing low sMBL levels and RVVI risk. Our findings contribute to the novel future research directions for the development of emerging MBL substitution as effectual therapy for RVVI.

FEVER AND RESPIRATORY DISTRESS IN AN INFANT: MANNOSE-BINDING LECTIN DEFICIENCY?

Introduction Mannose-binding lectin (MBL) plays an important role in innate immunity by mediating phagocytosis and complement-mediated destruction of pathogens. Decreased MBL levels have been associated with an increased susceptibility to herpes simplex virus, influenza A, Pseudomonas aeruginosa, and Staphylococcus aureus. MBL- deficient individuals typically present with upper respiratory tract infections, acute otitis media, or lupus-like symptoms. We present an infant with multiple infections who was diagnosed with MBL deficiency. Case Description This is a 7-week-old term male with a history of failure to thrive and acute otitis media. He was admitted with fever, respiratory distress, and new onset seizures. A respiratory panel was positive for Influenza B, Enterovirus, and Rhinovirus. Physical exam was significant for hepatomegaly and a desquamating rash on his lips, buttocks, and left hand consistent with possible Staphylococcus scalded skin syndrome, treated with antibiotics. An immunodeficiency was suspected because of multiple infections. Laboratory work-up revealed a positive blood culture to MRSA and low mannose-binding lectin levels (initial 11.9 ng/mL, repeat 3 ng/mL - normal range >50 ng/mL). Lymphocyte subsets (T, B and NK cells), quantitative immunoglobulins (IgA, IgM, and IgG), and CH50 were all normal. He was diagnosed with MBL deficiency. Discussion MBL deficiency is a poorly understood disorder of the innate immune system. There have been limited reports of MBL deficiency despite a high prevalence in certain populations. This case highlights the importance of having innate immune system defects in the differential diagnosis for early diagnosis and management of patients with a history of multiple infections. Mannose-binding lectin (MBL) plays an important role in innate immunity by mediating phagocytosis and complement-mediated destruction of pathogens. Decreased MBL levels have been associated with an increased susceptibility to herpes simplex virus, influenza A, Pseudomonas aeruginosa, and Staphylococcus aureus. MBL- deficient individuals typically present with upper respiratory tract infections, acute otitis media, or lupus-like symptoms. We present an infant with multiple infections who was diagnosed with MBL deficiency. This is a 7-week-old term male with a history of failure to thrive and acute otitis media. He was admitted with fever, respiratory distress, and new onset seizures. A respiratory panel was positive for Influenza B, Enterovirus, and Rhinovirus. Physical exam was significant for hepatomegaly and a desquamating rash on his lips, buttocks, and left hand consistent with possible Staphylococcus scalded skin syndrome, treated with antibiotics. An immunodeficiency was suspected because of multiple infections. Laboratory work-up revealed a positive blood culture to MRSA and low mannose-binding lectin levels (initial 11.9 ng/mL, repeat 3 ng/mL - normal range >50 ng/mL). Lymphocyte subsets (T, B and NK cells), quantitative immunoglobulins (IgA, IgM, and IgG), and CH50 were all normal. He was diagnosed with MBL deficiency. MBL deficiency is a poorly understood disorder of the innate immune system. There have been limited reports of MBL deficiency despite a high prevalence in certain populations. This case highlights the importance of having innate immune system defects in the differential diagnosis for early diagnosis and management of patients with a history of multiple infections.

Possible Role of Chitin-Like Proteins in the Etiology of Alzheimer's Disease.

Chitin is a β-linked straight chain carbohydrate matrix monopolymer prominent in invertebrates, from fungi to arthropods. Surprisingly, chitin is now documented in vertebrates, including humans, a component of vertebrate physiology that has been neglected until now. Chitin levels are elevated in Alzheimer's disease (AD) patients, not only in the central nervous system but also in the cerebrospinal fluid and plasma. Elevated levels of chitin lectin have been reported in patients with AD. Chitinase activity varies widely in the human population. Chitin levels can increase in individuals with intrinsically low chitinase activity. Elevated amounts of chitin can reflect accumulation of the small chitin fragments that remain wherever rapid hyaluronan synthesis occurs. Another source of chitin may be from remote fungal infections. Chitin can be toxic for neurons, and its accumulation may lead to the development of AD. We present new suggestions for animal models and treatment modalities that could prove useful in future research endeavors. An unexpected connection with Gaucher's disease patients and their heterozygote relatives is also identified. These chitin-related mechanisms are novel approaches to AD whose etiology until now has defied explication.

Intradialytic Complement Activation Precedes the Development of Cardiovascular Events in Hemodialysis Patients.

Background: Hemodialysis (HD) is a life-saving treatment for patients with end stage renal disease. However, HD patients have markedly increased rates of cardiovascular morbidity and mortality. Previously, a link between the complement system and cardiovascular events (CV-events) has been reported. In HD, systemic complement activation occurs due to blood-to-membrane interaction. We hypothesize that HD-induced complement activation together with inflammation and thrombosis are involved in the development of CV-events in these patients.Methods: HD patients were followed for the occurrence of CV-events during a maximum follow-up of 45 months. Plasma samples were collected from 55 patients at different time points during one HD session prior to follow-up. Plasma levels of mannose-binding lectin, properdin and C3d/C3 ratios were assessed by ELISA. In addition, levels of von Willebrand factor, TNF-α and IL-6/IL-10 ratios were determined. An ex-vivo model of HD was used to assess the effect of complement inhibition.Results: During median follow-up of 32 months, 17 participants developed CV-events. In the CV-event group, the C3d/C3-ratio sharply increased 30 min after the start of the HD session, while in the event-free group the ratio did not increase. In accordance, HD patients that developed a CV-event also had a sustained higher IL-6/IL-10-ratio during the first 60 min of the HD session, followed by a greater rise in TNF-α levels and von Willebrand factor at the end of the session. In the ex-vivo HD model, we found that complement activation contributed to the induction of TNF-α levels, IL-6/IL-10-ratio and levels of von Willebrand factor.Conclusions: In conclusion, these findings suggest that early intradialytic complement activation predominantly occurred in HD patients who develop a CV-event during follow-up. In addition, in these patients complement activation was accompanied by a pro-inflammatory and pro-thrombotic response. Experimental complement inhibition revealed that this reaction is secondary to complement activation. Therefore, our data suggests that HD-induced complement, inflammation and coagulation are involved in the increased CV risk of HD patients.

Complement receptor 1 (CR1, CD35) association with susceptibility to leprosy

BackgroundPathophysiological mechanisms are still incompletely understood for leprosy, an urgent public health issue in Brazil. Complement receptor 1 (CR1) binds complement fragments C3b/C4b deposited on mycobacteria, mediating its entrance in macrophages. We investigated CR1 polymorphisms, gene expression and soluble CR1 levels in a case-control study with Brazilian leprosy patients, aiming to understand the role of this receptor in differential susceptibility to the disease.MethodologyNine polymorphisms were haplotyped by multiplex PCR-SSP in 213 leprosy patients (47% multibacillary) and 297 controls. mRNA levels were measured by qPCR and sCR1 by ELISA, in up to 80 samples.Principal findingsIndividuals with the most common recombinant haplotype harboring rs3849266*T in intron 21 and rs3737002*T in exon 26 (encoding p.1408Met of the York Yka+ antigen), presented twice higher susceptibility to leprosy (OR = 2.43, p = 0.017). Paucibacillary patients with these variants presented lower sCR1 levels, thus reducing the anti-inflammatory response (p = 0.040 and p = 0.046, respectively). Furthermore, the most ancient haplotype increased susceptibility to the multibacillary clinical form (OR = 3.04, p = 0.01) and presented the intronic rs12034383*G allele, which was associated with higher gene expression (p = 0.043), probably increasing internalization of the parasite. Furthermore, there was an inverse correlation between the levels of sCR1 and mannose-binding lectin (initiator molecule of the lectin pathway of complement, recognized by CR1) (R = -0.52, p = 0.007).ConclusionsThe results lead us to suggest a regulatory role for CR1 polymorphisms on mRNA and sCR1 levels, with haplotype-specific effects increasing susceptibility to leprosy, probably by enhancing parasite phagocytosis and inflammation.

A relationship between chronic obstructive pulmonary disease, obesity and melatonin level

This is a review of experimental and clinical studies investigated effects of obesity on clinical course of chronic obstructive pulmonary disease (COPD); pathophysiological mechanisms of this effect, and relationships between melatonin level and the course of COPD have been also discussed. Associations between severity of COPD, rate of exacerbations and blood levels of most important adipokines, such as leptin and adiponectin, and relationships between melatonin levels and those adipokines were published. Conflicting results were obtained in studies of effects of obesity on clinical course of COPD. The "obesity paradox", that is a reduction in mortality and milder bronchial obstruction in obese COPD patients, has been identified in several studies. Despite contradictory results, obesity is likely to improve prognosis of COPD due to decrease in the systemic inflammation. Levels of leptin and adiponectin increase in acute exacerbation of COPD and then decrease to the baseline. Moreover, melatonin is suggested to play a great role for COPD course, mostly due to antiinflammatory and antioxidant activities. According to results of several studies, melatonin could affect blood levels of adiponectin and lectin; this could indirectly influence on the systemic inflammation in COPD. Further studies are needed to elicit these relationships.

Phytogenic feed-additive effects on channel catfish rhamnose-binding lectin levels, and susceptibility to Edwardsiella ictaluri.

We investigated the effects of a phytogenic feed additive on disease susceptibility to Edwardsiella ictaluri in channel catfish Ictalurus punctatus and regulation of 6 rhamnose-binding lectin (RBL) genes. Juvenile catfish (n = 250, 13.4 ± 0.1 g) were allotted to the following treatments: control (floating diet) or EO (floating diet supplemented with essential oils; Digestarom® P.E.P. MGE). The fish were fed their respective diets for 6 wk. Following subjection to different feed treatments, all fish were exposed to pathogenic E. ictaluri by bath immersion. Another group of fish were not challenged (non-challenged controls, fed control feed). Mucosal tissue samples were taken to quantify gene expression levels of RBL on Days 1 and 2 post-challenge. After challenge, survival was higher (64.4 vs. 48.0%) in fish fed EO compared to controls (p < 0.05). Relative to non-challenged controls, gill RBL1a mRNA was higher in fish fed EO (p < 0.05) on Day 1 while gill RBL3b was higher in fish fed EO (p < 0.01) on Days 1 and 2, respectively. RBL5a in the skin and proximate small intestine did not change significantly relative to non-challenged fish on Days 1 and 2 of the disease challenge. Results demonstrate that Digestarom® P.E.P. MGE improved survival of channel catfish challenged with E. ictaluri. One of the mechanisms through which essential oils may improve survival is through upregulation of RBL1a and RBL3b in the gill.

Serum mannose-binding lectin as a biomarker in neonatal sepsis

Objective The aim of thi s study was to evaluate the levels of mannose-binding lectin (MBL) in neonates to determine the relation between MBL deficiency and the development of sepsis. Background The MBL is a member of the collection family that is produced by the liver as an acute-phase protein. MBL activates macrophages, enhances phagocytosis, and contributes toward complement activation. Low serum MBL levels increase the risk of infections, especially if associated with other conditions such as immune deficiencies of various origins. Neonates are considered to be immunocompromised because their adaptive immunity has not yet been developed. Patients and methods This case–control study was carried out on 86 neonates classified into two groups: 45 neonates diagnosed with sepsis and 41 healthy neonates with no clinical signs or laboratory evidence of sepsis who were enrolled as a control group. Assessment of history, clinical examination, and investigations (complete blood count, C-reactive protein, blood culture, MBL levels) were performed for all neonates. Results The mean MBL serum level was found to be lower in the septic group (0.49 ± 0.1) than the control group (1.4 ± 0.3) with high statistical significance. Conclusion Low MBL serum levels are related to the development of sepsis.

The Chinese herbal formula Zhibai Dihuang Granule treat Yin-deficiency-heat syndrome rats by regulating the immune responses

Ethnopharmacological relevanceZhibai Dihuang Granule (ZDG), a traditional Chinese medicine (TCM) made from eight Chinese herbs, has been classically used to treat Yin-deficiency-heat (YDH) syndrome. ZDG is well known with the therapeutic efficacy of nourishing Yin and decreasing internal heat in clinic, but the mechanism of ZDG's therapeutic effect is still not clear. Materials and methodsHigh doses of triiodothyronine (T3) were given intraperitoneally to induce Hyperthyroid YDH syndrome in SD rats. The animals were then treated with ZDG for one week. The iTRAQ-coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) technique was used to screen the differentially expressed serum proteins between ZDG treated rats and YDH syndrome rats. The differentially expressed proteins were analyzed by bioinformatics method and were verified by enzyme-linked immunosorbent assay (ELISA). ResultsA total of 55 differentially expressed proteins were identified, including 23 up-regulated proteins (>1.25 fold, p < 0.05) and 32 down-regulated proteins (<0.80 fold, p < 0.05). Among the differentially expressed proteins, 26 proteins returned to normal after ZDG treatment. Bioinformatics analysis showed that these proteins were mainly involved in immune response, including regulation of immune system process, complement activation, and humoral immune response mediated by circulating immunoglobulin. ELISA revealed significantly increased levels of Zinc-alpha-2-glycoprotein (Azgp1), L-selectin, C-reactive protein (Crp), Plasminogen (Plg), Kininogen 1 (Kng1), and significantly decreased levels of Mannose binding lectin 2 (Mbl2) and Complement C1qb chain (C1qb) in ZDG treated rats compared with YDH syndrome rats. Bioinformatics analyses indicated that Azgp1 participated in antigen processing and presentation, Crp, C1qb, and Mbl2 were involved in complement activation, while L-selectin, Plg, and Kng1 were involved in regulating the inflammatory response. ConclusionsOur study provides experimental evidence to understand the therapeutic mechanism of ZDG in YDH syndrome. The results suggested that ZDG may regulate the complement activation and inflammatory response, and promote the ability to recognize antigens to alleviate YDH syndrome.

Identification of dysfunctional CD8+ T-cell subsets rescued by PD-L1 blockade in the tumor microenvironment

Abstract While depletion studies using mice clearly show that CD8+ T cells are of crucial importance in anti-tumor efficacy, gaps in understanding the exact mechanisms that regulate CD8+ T cell responses in the tumor microenvironment (TME) are a major impediment in efforts to improve immunotherapy. We have evaluated phenotypical and functional heterogeneity of tumor-infiltrating lymphocytes (TILs) after adoptive transfer of ex vivo primed Pmel-1 T-cell receptor transgenic CD8+ T cells specific for the gp100 antigen expressed on B16 melanoma. We found that the chemokine receptor, CX3CR1 identifies distinct effector CD8+ T-cell subsets, CX3CR1 negative (−), intermediate (int), and high (hi) in the TME. A CX3CR1hi subset contained terminally-differentiated CD8+ T cells that express higher levels of killer-cell lectin like receptor G1 (KLRG1), TNF-related apoptosis-inducing ligand (TRAIL), perforin, and granzyme A. Significantly more CX3CR1int CD8+ T cells expressed CD25 compared to other subsets, suggesting this is the subset that is rapidly proliferate and generate terminally-differentiated T cells. Unexpectedly, despite their terminally differentiated status, a CX3CR1hi subset expressed significantly lower levels of co-inhibitory receptors, PD-1, LAG3, and TIGIT compared to CX3CR1− and CX3CR1int subsets in the TME. In line with this, proliferation and cytokine production of CX3CR1− and CX3CR1int subsets were significantly decreased in the TME compared to a CX3CR1hi subset. Importantly, functional burst after PD-L1 blockade came almost exclusively from CX3CR1− and CX3CR1int subsets. These findings provide a better understanding of dysfunctional CD8+ TILs and can be exploited to develop more effective cancer immunotherapy.

Changes in levels of phytic acid, lectins and oxalates during soaking and cooking of Canadian pulses

Raw and processed (soaked or cooked) seeds of peas, lentils, chickpeas, fava beans and common beans were studied for their contents of antinutritional factors (lectins, phytic acid, total and soluble oxalates), along with soybean as a control. Analysis of variance indicated that legume type, treatment and their interactive effects were significant on these antinutrients. The raw soybean seed was found to contain the highest levels of lectins (692.8 HU/mg), phytic acid (22.91 mg/g), total oxalate (370.5 mg/100 g) and soluble oxalate (200.7 mg/100 g) among all investigated seeds. Relatively high contents of lectins were detected in beans (87.69–88.59 HU/mg) and other pulses ranging from 2.73–11.07 HU/mg. Phytic acid in Canadian pulses varied slightly from 8.55–22.85 mg/g. Total oxalates were variable, ranging from 244.7–294.0 mg/100 g in peas, 168.6–289.1 mg/100 g in lentils, 241.5–291.4 mg/100 g in fava beans, 92.2–214.0 mg/100 g in chickpeas and 98.86–117.0 mg/100 g in common beans. Approximately 24–72% of total oxalate appeared to be soluble in all investigated pulses. Soaking the seeds in distilled water significantly decreased the contents of lectins (0.11–5.18%), total oxalate (17.40–51.89%) and soluble oxalate (26.66–56.29%), but had no impact on phytic acid. The cooking process was found to be more effective in reducing levels of all the investigated antinutritional factors, except phytic acid in common beans and soybean.

Low Levels of Immunoglobulins and Mannose-Binding Lectin Are Not Associated With Etiology, Severity, or Outcome in Community-Acquired Pneumonia.

BackgroundDisease severity and outcome in community-acquired pneumonia (CAP) depend on the host and on the challenge of the causal microorganism(s). We measured levels of immunoglobulins (Igs) and complement in 257 hospitalized adults with CAP and examined the association of low levels of Igs or complement to microbial etiology, disease severity, and short-term and long-term outcome.MethodsSerum Igs were analyzed in blood samples obtained at admission and at 6 weeks postdischarge if admission levels were low. Serum complement deficiencies were screened with a total complement activity enzyme-linked immunosorbent assay (ELISA), with further analyzes performed if justified. Disease severity was assessed by the CURB-65 severity score. Short-term outcome was defined as a composite end point of intensive care unit (ICU) admission and 30-day mortality, and long-term outcome as 5-year all-cause mortality.ResultsAt admission, 87 (34%) patients had low levels of at least 1 Ig, with low IgG2 as the most prevalent finding (55/21%). IgG levels were lower in bacterial than viral CAP (8.48 vs 9.97 g/L, P = .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 not substantially affect these results.ConclusionIn hospitalized adults with CAP, low admission levels of Igs or complement were in general not associated with microbial etiology, disease severity, short-term outcome, or long-term outcome.

Functional mannose binding lectin levels in patients with pediatric onset systemic lupus erythematosus in remission.

Complement system plays a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Excessive activation of complement causes tissue injury and SLE occurrence is typically associated with congenital deficiencies of the early components of the classical complement pathway. Mannose-binding lectin (MBL) is recognized as important causative factor in the etio-pathogenesis of SLE and MBL-2 gene has evolved as a candidate gene for SLE susceptibility. This study was done to assess the functional MBL (fMBL) level in SLE patients in remission and its co-relation with disease severity and outcome. Functional MBL levels were compared with age and sex matched healthy controls and were correlated with duration of illness,complement levels and anti-double- stranded DNA antibody levels. Mean fMBL level in patients was found to be 696.19±408.98U/mL and 579.52±393.87U/mL in the control group. Four children had very low fMBL levels (<40U/mL). Functional MBL levels were higher in patients with SLE even when the disease was in remission as compared to healthy controls, although not statistically significant. Large variation exists in fMBL levels in patients with SLE even when in remission. Very low fMBL levels were found in some children with younger age of onset of SLE, multisystem involvement and severe course of the disease. Positive correlation of MBL levels with anti-ds DNA titers suggest that its values vary with activity and could be a potential biomarker of the disease.

Circulating levels of mannose-binding lectin (MBL) in age-related macular degeneration.

To assess whether the serum levels of mannose-binding lectin of the lectin complement pathway are associated with age-related macular degeneration. Patients with age-related macular degeneration and age-matched controls underwent full ophthalmologic examination and optical coherence tomography. Using a time-resolved immunofluorometric assay, blood samples were evaluated to determine the serum mannose-binding lectin levels. A total of 136 individuals were evaluated, including 68 patients with age-related macular degeneration (34 exudative and 34 nonexudative) and 68 age-matched controls. The median mannose-binding lectin level was 608 ng/mL (range, 30-3,415 ng/mL) in patients with age-related macular degeneration and 739 ng/mL (range, 30-6,039 ng/mL) in controls, with no difference between the groups. Additionally, the median mannose-binding lectin level was 476 ng/mL (range, 30-3,415 ng/mL) in exudative cases and 692 ng/mL (range, 30-2,587 ng/mL) in nonexudative cases. Serum mannose-binding lectin levels were not associated with age-related macular degeneration or with the exudative and nonexudative forms of the disease.

Risk assessment of antinutrient consumption of plant foods of south eastern Nigeria.

The risk assessment of anti-nutrient of consumed plant food of South Eastern Nigeria were estimated from actual quantity of plant food diet and the values compared with known risks levels from existing biological studies. The foods studied were yam, rice, garri, cassava fufu, tapioca and cowpea. Using the proportion of anti-nutrient composition of the plant food by weight, the anti-nutrients consumed were calculated from the weight of consumed food. The antinutrients were measures in mg/kg of food. The results show that the levels of lectin (0.05 mg.kg), cyanide (0.21-5.78 mg/kg) acceptable by existing studies while levels of phytate (23.5-130.65 mg/ kg), oxalate (4.7-95.6 mg/kg) and tannin (108.3 mg/kg) are high enough to be associated with health risk and further studies should be carried out to authenticate Maximum Residual Limits (MRL) of these ante nutrients in human to determine whether the levels on the foods consumed should be reduced or allow them as they are.

Serum mannan-binding lectin in patients with pulmonary tuberculosis: Its lack of a relationship to the disease and response to treatment.

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.

Prospective Observational Study on the Association Between Serum Mannose-Binding Lectin Levels and Severe Outcome in Critically Ill Patients with Pandemic Influenza Type A (H1N1) Infection.

BackgroundMannose-binding lectin (MBL) plays an important role in the innate immune response. In addition to activating the complement, MBL can induce cytokine production and contribute to a deleterious inflammatory response with severe A(H1N1)pdm09 virus infection. Our aim was to determine if serum MBL levels correlate with the risk of mortality in intensive care units (ICU) patients with A(H1N1)pdm09 infection.MethodsProspective observational study was performed in ICU patients with acute respiratory distress syndrome due to influenza A(H1N1)pdm09 virus. Demographic characteristics and severity indices were recorded at ICU admission. MBL was assayed from blood drawn at influenza diagnosis within 24–48 h following the ICU admission. Outcomes were compared according to MBL levels. Results are expressed as median and interquartile range.ResultsSerum MBL levels were studied in 27 patients (age: 56 [IQR 29] years) with severe A(H1N1)pdm09 infection and in 70 healthy controls. Median admission SAPSII and SOFA scores were 49 [IQR 26] and 12 [IQR 5], respectively. Mortality rate after a 30-day was 37%. MBL was significantly higher in non-survivors (3741 [IQR 2336] ng/ml) vs survivors (215 [IQR 1307] ng/ml), p = 0.006, as well as control group (1814 [IQR 2250] ng/ml), p = 0.01. In contrast, MBL levels in survivors group were significantly lower than the controls group (215 [IQR 1307] ng/ml vs. 1814 [IQR 2250] ng/ml, p = 0.005). MBL cut-off > 1870 ng/ml had a sensitivity of 80% and a specificity of 88.2% for mortality [AUC = 0.82 (95% CI 0.63–0.94)]. Kaplan–Meier analysis demonstrated a strong association between MBL levels and mortality (log-rank 7.8, p = 0.005). MBL > 1870 ng/ml was independently associated with mortality (HR = 8.7, 95% CI 1.2–29.1, p = 0.007).ConclusionsThis study shows that baseline MBL > 1870 ng/ml is associated with higher mortality in ICU patients with severe A(H1N1)pdm09 infection.

Pathogen invasion changes the intestinal microbiota composition and induces innate immune responses in the zebrafish intestine

Numerous bacteria are harbored in the animal digestive tract and are impacted by several factors. Intestinal microbiota homeostasis is critical for maintaining the health of an organism. However, how pathogen invasion affects the microbiota composition has not been fully clarified. The mechanisms for preventing invasion by pathogenic microorganisms are yet to be elucidated. Zebrafish is a useful model for developmental biology, and studies in this organism have gradually become focused on intestinal immunity. In this study, we analyzed the microbiota of normal cultivated and infected zebrafish intestines, the aquarium water and feed samples. We found that the predominant bacteria in the zebrafish intestine belonged to Gammaproteobacteria (67%) and that feed and environment merely influenced intestinal microbiota composition only partially. Intestinal microbiota changed after a pathogenic bacterial challenge. At the genus level, the abundance of some pathogenic intestinal bacteria increased, and these genera included Halomonas (50%), Pelagibacterium (3.6%), Aeromonas (2.6%), Nesterenkonia (1%), Chryseobacterium (3.4‰), Mesorhizobium (1.4‰), Vibrio (1‰), Mycoplasma (0.7‰) and Methylobacterium (0.6‰) in IAh group. However, the abundance of some beneficial intestinal bacteria decreased, and these genera included Nitratireductor (0.8‰), Enterococcus (0.8‰), Brevundimonas (0.7‰), Lactococcus (0.7‰) and Lactobacillus (0.4‰). Additionally, we investigated the innate immune responses after infection. ROS levels in intestine increased in the early stages after a challenge and recovered subsequently. The mRNA levels of antimicrobial peptide genes lectin, hepcidin and defensin1, were upregulated in the intestine after pathogen infection. These results suggested that the invasion of pathogen could change the intestinal microbiota composition and induce intestinal innate immune responses in zebrafish.

Mannose-binding lectin deficiency and miscarriages in rheumatoid arthritis

Objective: To investigate the association between mannose-binding lectin (MBL) serum level and MBL2 polymorphisms, and the frequency of spontaneous miscarriages in rheumatoid arthritis (RA) patients.Methods: One hundred seventy seven women (mean age 50 years) with RA from Southern Brazil were studied and 4.5% had a history of abortion (8/177). The MBL levels were determined by ELISA. MBL2 polymorphisms in the promoter (−550H/L, −221X/Y), 5′ untranslated region (4 P/Q) and exon 1 (p.Gly54Asp: B allele, p.Arg52Cys: D allele and p.Gly57Glu: C allele; collectively labelled O) were genotyped by sequencing.Results: Mannose-binding lectin levels of RA patients ranged from ≤100 ng/mL to 6640 ng/mL (median 541.5 ng/mL). There was a significant difference in MBL median levels (100 ng/mL vs. 625 ng/mL, respectively, p = .001) and frequency of MBL deficiency (75.0% vs. 24.1%, p = .007, OR = 10.3, 95%CI = 1.9–55.4), in patients with a history of miscarriage vs those without it. Patients with RA and miscarriage had more frequently haplotypes related with low MBL levels (p = .007, OR = 10.5, 95%CI = 1.3–84) than high producers. Moreover, LYPB haplotype and O allele were significantly associated with the occurrence of miscarriage (p = .001, OR = 9.7, 95%CI = 2.4–39.1 and p = .009, OR = 5.9, 95%CI = 1.4–23.4, respectively).Conclusions: The results suggest that MBL deficiency and the presence of MBL2 gene polymorphisms that lead to MBL deficiency are risk factors for the occurrence of miscarriage in patients with RA.

Low circulating mannan-binding lectin levels correlate with increased frequency and severity of febrile episodes in myeloma patients who undergo ASCT and do not receive antibiotic prophylaxis.

Patients with multiple myeloma (MM) who undergo autologous stem cell transplantation (ASCT) are susceptible to severe infections. Low levels of circulating mannan-binding lectin (MBL) are associated with increased risk of infection. In this prospective study, we evaluated 100 patients who underwent ASCT regarding the effect of MBL on the incidence and severity of febrile episodes. Seventeen patients had MBL levels <500 ng/mL (11 received antibiotic prophylaxis and 6 did not). Although there was no statistical difference regarding the development of febrile episodes between patients with low and normal MBL, among 17 patients with low MBL levels, six out of eleven patients who received antibiotic prophylaxis developed a febrile episode compared with six out of six patients who did not receive antibiotic prophylaxis and developed a febrile episode. Patients with low MBL levels who responded less frequently to first line antibiotic therapy required more frequent administration of a second more advanced line of antibiotics, independently of receiving or not prophylaxis, and required prolonged hospitalization. In the univariate analysis low MBL associated with shorter OS. Our results suggest that patient with low MBL levels should receive antibiotic prophylaxis to reduce the number of febrile episodes and raise the issue of MBL replacement for these patients.