Serum Mannose-binding Lectin Levels Research Articles

Mannose-Binding Lectin Gene Variants as Disease Susceptibility Biomarkers in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease characterized by progressive destruction of peripheral joints. About 1% of the human population worldwide is suffering from this disease. The pathophysiology of RA is largely being influenced by immune dysregulation. Mannose-binding lectin (MBL), an acute-phase protein, has been reported to play an important role in pathogenesis of RA by the activation of complement pathway. Various studies documented the established the role of MBL in pathogenesis of various autoimmune diseases, including RA. MBL protein is encoded by gene MBL2, mapped on chromosome 10q11.2-q21. Objective: Both MBL serum levels and activity are mainly determined genetically by its variants. So considering the putative clinical role of MBL2, this case-control association study was designed to assess its six functional variants in a northwestern Indian cohort. Methods: Genetic typing of six MBL2 variants was done by amplification refractory mutation system-polymerase chain reaction. Data were analyzed using suitable statistical tools. Results: Significant difference has been observed in genotypic and allelic distribution between cases and controls for rs11003125. Comparison of allelic distribution for rs1800450 showed significantly high prevalence of A allele in cases than controls. Conclusion: These results indicate that MBL2 variants may act as plausible marker for susceptibility toward RA. Keeping this in view, it is pertinent to screen these variants in other population groups of India.

Combined clinical significance of MRI and serum mannose-binding lectin in the prediction of spinal tuberculosis

BackgroundSpinal tuberculosis (STB) is a local manifestation of systemic infection caused by Mycobacterium tuberculosis, accounting for a significant proportion of joint tuberculosis cases. This study aimed to explore the diagnostic value of MRI combined with mannose-binding lectin (MBL) for STB.Methods124 patients suspected of having STB were collected and divided into STB and non-STB groups according to their pathological diagnosis. Serum MBL levels were measured using ELISA and a Pearson analysis was constructed to determine the correlation between MBL and STB. ROC was plotted to analyze their diagnostic value for STB. All the subjects included in the study underwent an MRI.ResultsThe sensitivity of MRI for the diagnosis of STB was 84.38% and specificity was 86.67%. The serum MBL levels of the patients in the STB group were significantly lower than the levels in the non-STB group. ROC analysis results indicated that serum MBL’s area under the curve (AUC) for diagnosis of STB was 0.836, with a sensitivity of 82.3% and a specificity was 77.4%. The sensitivity of MRI combined with MBL diagnosis was 96.61%, and the specificity was 92.31%, indicating that combining the two diagnostic methods was more effective than using either one alone.ConclusionsBoth MRI and MBL had certain diagnostic values for STB, but their combined use resulted in a diagnostic accuracy than either one alone.

Mannose Binding Lectin and C3 Serum Levels in Coronary Artery Disease: A Cross-Sectional Study

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

Patterns of Mannose-Binding Lectin (MBL) responses to <i>Plasmodium falciparum</i> infections in hyperendemic settings

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

Association between mannose binding lectin gene polymorphisms and clinical severity of COVID-19 in children.

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

Mannose-binding lectin gene 2 variant DD (rs 5030737) is associated with susceptibility to COVID-19 infection in the urban population of Patna City (India).

The study aimed to measure plasma levels of Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) and theirpolymorphisms in COVID-19 patients and controls to detect association. As MBL is a protein of immunological importance, it may contribute to the first-line host defence against SARS-CoV-2. MBL initiates the lectin pathway of complement activation with help of MASP-1 and MASP-2. Hence, appropriate serum levels of MBL and MASPs are crucial in getting protection from the disease. The polymorphisms of MBL and MASP genes affect their plasma levels, impacting their protective function and thus may manifest susceptibility, extreme variability in the clinical symptoms and progression of COVID-19 disease. The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively.The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively. Our results indicate that median serum levels of MBL and MASP-2 were significantly low in diseased cases but attained normal levels on recovery. Only genotypeDD was found to be associated with COVID-19 cases in the urban population of Patna city.

5588568 ASSOCIATION OF MANNOSE-BINDING LECTIN SERUM LEVEL AND PROMOTER GENE VARIANTS RS7096206 AND RS10031251 WITH FREQUENCY OF VASO-OCCLUSIVE EVENTS IN SICKLE CELL DISEASE PATIENTS; AN EGYPTIAN CROSS-SECTIONAL STUDY

Background: Sickle cell disease (SCD) is a genetic blood disorder involving hemoglobin alterations, in addition to endothelial adhesion, thrombosis and inflammation. Low serum Mannose-binding lectin (MBL) levels can enhance SCD-related blood vessel inflammation as well as reduction of phagocytic activity, leading to sickled erythrocyte accumulation on vessel walls and impaired ability to combat infections. This may contribute to the vaso-occlusive (VOC) episodes. Aim: This work aimed to investigate serum MBL level and MBL promoter gene variants distribution among a cohort of Egyptian SCD patients and to describe their association with VOC events frequencies in the studied patients. Methods: This cross-sectional study included 88 steady-state Egyptian SCD patients aged 6-18 years diagnosed and followed up at Pediatric Hematology Unit, Cairo University Children Hospital. Informed consent was obtained willingly from all subjects or their guardians before enrolment in the study. MBL promoter (-221) (rs7096206) X/Y and (-550) (rs10031251) H/L gene variants were studied by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Serum MBL level was assayed by ELISA technique with values <500ng/ml considered deficient. Results: The median serum MBL level in SCD patients was 130.9 ng/ml (IQR 71.2-323.9 ng/ml). Patients with serum MBL levels <500ng/ml were significantly older, had longer disease duration and higher rate of VOCs per year, VOCs per lifetime and a higher VOC index (p= 0.039, 0.034, 0.047, 0.040 and 0.008 respectively). Levels <500ng/ml predominated in SS (89.4%) than Sβ groups (70%) (p= 0.023) and in patients with high frequency of VOCs (91.4%) (p=0.008). Serum MBL level correlated negatively with patients’ age, disease duration, hydroxyurea total treatment duration, blood transfusions per lifetime and steady-state HbS level (p= <0.001, <0.001, 0.011, 0.014, 0.031 respectively) but correlated positively with steady-state HbF level (p=0.002). MBL (-221) X/Y both alleles were more associated with (H) allele of MBL (-550) than with L allele (p=0.048), however, with no statistically significant genotype distribution between the studied variants. There was no statistically significant difference in genotype distribution or allele frequencies between MBL (-221) and MBL (-550) in SCD patients regarding serum MBL level, sickle cell type (SS and Sβ), VOCs frequencies or disease severity classes. Conclusion: Serum MBL level rather than studied MBL gene variants is more likely to contribute to the clinical outcomes of SCD; patients with lower MBL levels had a higher rate of VOC per year, per lifetime and a higher VOC index. Meanwhile, the variant genotypes and alleles of the studied MBL promotor gene variants were not associated with MBL deficiency, VOCs, infection events, and disease severity.Further studies to investigate other polymorphisms in MBL gene; MBL exon-1 (codons 52,54 and 57) are recommended. Keywords: MBL, Polymorphism, Sickle cell disease, Vaso-occlusive crises, Egypt

The relationship between COVID-19 and the complement system: mannose-binding lectin.

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

Association between serum levels of pentraxin-3, mannose binding lectin and high sensitivity C-reactive protein with renal transplantation

Introduction: Chronic kidney disease (CKD) may increase morbidity and mortality. Therefore, early detection of inflammation in kidney transplant recipients with a high risk of transplant rejection is important. Objectives: This study was conducted to compare serum levels of pentraxin-3 (PTX-3), mannose binding lectin (MBL) and high sensitivity C-reactive protein (hs-CRP) in patients with chronic renal failure before and after transplantation. Patients and Methods: This cross-sectional study was carried on 18-80 years old patients receiving immunosuppressive therapy who underwent kidney transplantation in Shahid Beheshti hospital of Babol in 2016. Before transplantation, one week later and two months after transplantation, the serum levels of PTX-3, MBL and hs-CRP were determined. Complications including acute transplant rejection and urinary tract infection were recorded since inflammatory markers were evaluated and compared at the time of complication. Results: The mean age of the patients was 42.07±12.47 years. Transplant rejection and urinary tract infection occurred in 3 (10%) and 4 (13.3%) of patients, respectively. Patients over 55 years of age and those with hypertension had significantly more complications (P=0.03 and P=0.02 respectively). Two months after transplantation, PTX-3 and MBL levels were significantly lower (PTX-3; 10.84±15.88 versus18.75±24.31 ng/dL, P=0.001 and MBL; 764.3±771.35 versus 1157.9±1299.75 ng/dL, P=0.006). In patients with complications, PTX-3, MBL and hs-CRP levels were 16.73±27.98 ng/dL, 710.0±613.19 ng/dL and 8.43±12.10 mg/L, respectively. No significant difference was found between inflammatory markers in complicated and uncomplicated patients. Comparison of changes in PTX-3, MBL and hs-CRP levels before and after transplantation showed a significant difference two months following transplantation compared to pre-transplantation and also one week after it for PTX-3 and MBL (PTX-3: P=0.001 and P=0.009, respectively; MBL: P=0.006 and P=0.03, respectively). Conclusion: Based on the results of this study, PTX-3 and MBL levels can be considered for determining the inflammatory status of kidney transplant patients and the prognosis of transplantation.

Association of the Mannose-Binding Lectin 2 BB Genotype with COVID-19-Related Mortality

Mannose-binding lectin (MBL) is crucial in first-line immune defenses. There are still many unknown factors regarding the mechanisms causing variability in the clinical course of coronavirus disease 2019 (COVID-19). In Japan, there have been few reports to date regarding the association between MBL and COVID-19. It has been demonstrated that the MBL2 gene B variant at codon 54 (rs1800450) is associated with variabilities in the clinical course of COVID-19. We aimed to investigate how the level of serum MBL and the codon 54 variant of MBL (rs1800450) affect the disease severity of COVID-19. A total of 59 patients from the fourth wave and 49 patients from the fifth wave in Japan were analyzed based on serum MBL levels using ELISA and the genotype of MBL2 codon 54 using PCR reaction. There was no significant association between serum MBL levels and age. MBL2 genotype was independent of age, there was no significant difference in different COVID-19 severities, MBL genotypes, and serum MBL levels. Binary logistic regression analysis to identify predisposing factors for severe COVID-19 symptoms demonstrated that patients with the BB genotype had a higher risk of death from COVID-19. Our results quantitatively demonstrated that the BB genotype might be a factor associated with death from COVID-19.

Erysipelothrix rhusiopathiae-specific T-cell responses after experimental infection of chickens selectively bred for high and low serum levels of mannose-binding lectin

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

Gene polymorphisms and serum levels of mannose-binding lectin in Czech patients with recurrent aphthous stomatitis: A case-control study.

Recurrent aphthous stomatitis is one of the most prevalent oral mucosal immunological diseases. A recent case-control study in the Egyptian population suggested that single nucleotide polymorphism Gly54Asp (rs1800450) of the mannose-binding lectin 2 gene might affect the mannose-binding lectin serum level and recurrent aphthous stomatitis development. The aim of this study was to determine the distribution of six functional mannose-binding lectin 2 gene polymorphisms and analyse their role in recurrent aphthous stomatitis susceptibility in the Czech population. The study included 227 subjects; 137 healthy people and 90 patients with recurrent aphthous stomatitis. Six mannose-binding lectin 2 gene polymorphisms (rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, rs1800451) were analysed by the SNaPshot assay method, mannose-binding lectin serum levels were determined by enzyme-linked immunosorbent assay (ELISA) method in a subgroup of subjects (N=87). No significant differences in mean of mannose-binding lectin serum levels between healthy controls and patients with recurrent aphthous stomatitis were observed (383 ng/ml ± 249 standard deviation (SD) vs. 316 ng/ml ± 177 SD in remission phase vs. 343 ng/ml ± 254 SD in active phase; p > 0.05), also the allele and genotype frequencies of the studied mannose-binding lectin 2 polymorphisms did not differ significantly between the two groups (p > 0.05, odds ratio (OR): 0.75-1.23). Moreover, the distribution of mannose-binding lectin 2 haplotypes and haplogenotypes was similar in the healthy subjects and patients with recurrent aphthous stomatitis (p > 0.05, OR: 0.75-1.23). This study did not confirm the previously reported association of the mannose-binding lectin 2 Gly54Asp gene variant and low mannose-binding lectin serum level as the risk factors for susceptibility to recurrent aphthous stomatitis. In addition, no significant relationships between mannose-binding lectin 2 functional haplotypes or haplogenotypes and recurrent aphthous stomatitis were observed.

High Respiratory Tract Infection Rate in Patients With Familial Mediterranean Fever.

Background Familial Mediterranean fever (FMF) is a systemic autoinflammatory disease genetically transmitted with the autosomal recessive trait. Although the pathogenesis is not certain, it is known that there is a deficiency in the regulation of the natural immune system. In this study, we aimed to search whether patients with FMF are predisposed to respiratory tract infections and whether mannose-binding lectin (MBL), as a natural immune system member, contributes to it. Methods Fifty FMF patients and 20 control groups were enrolled in the study. First, the frequencies of upper respiratory tract infection (URTI) within the previous year of both patient and control groups were evaluated retrospectively. Then, both groups were followed up for URTI for one year after starting the study. The patient's immunoglobulin A (IgA), IgM, IgG, C-reactive protein (CRP), hemogram parameters, and mannose-binding lectin were evaluated. Results The median frequency of annual URTI with a retrospective evaluation of patients was higher than that of the control group. Also, the median frequency of URTI with the prospective evaluation of patients with FMF was higher than the control group.The rate of patients with low serum IgG levels was higher in the patient group than in the control group. However, serum IgG levels of FMF patients with frequent URTI were not different from those without. The median MBL levels of both groups were similar (1312 vs. 1534 ng/mlfor the patient and control group, respectively). The rate of patients having low serum MBL levels was also similar between the groups. Conclusions In the present study, we found that patients with FMF had more URTI than healthy controls. However, the underlying cause is not fully explained. There is a need for further studies with a higher number of patients evaluating URTI in patients with FMF.

Highly sensitive C-reactive protein, pentraxin-3 and mannose-binding lectin in patients with hemodialysis and their association with cardiovascular complications and mortality

Introduction: Cardiovascular disorder(CVD) is one of the most important comorbidities in patients with hemodialysis(HD). Several markers for kidney disease and kidney transplantation have been investigated. Objectives: This study aimed to evaluate the association between three inflammatory biomarkers including C-reactive protein (CRP), pentraxin 3 (PTX-3) and mannose-binding lectin (MBL) with CVD events and mortality in HD patients. Patients and Methods: This study was carried on patients with immunosuppressive therapy aged between 18-80 years with chronic renal failure undergoing HD. Patients were visited at baseline and every six month for 12 months. The levels of biomarkers and complications were recorded before, one week later and 2 months after transplantation. Echocardiography and calculation of ejection fraction(EF) were performed to determine the occurrence of CVD events. Results: Ninety patients with the mean age of 54.0±3.24 years were included. All biomarkers had significant area under the curve for accurate diagnosis between the patients with low EF (with a decreasing measure) and normal EF patients (p&lt;0.05); however, none of them had a significant accurate diagnosis between patients with low EF (with a constant measure) and normal EF patients (P&gt;0.05). PTX-3 and MBL showed a significant correlation to detect CVD events (r=0.987; p&lt;0.0001). Also, PTX-3 and MBL had significant correlations with hs-CRP (P&lt;0.05). None of these markers had significant accuracy for prediction of mortality. Conclusion: Serum level of PTX-3 and MBL not only increase reactive protein, but also may be considered as diagnostic biomarkers for early detection of CVD events in patients with end stage renal disorders.

Serum Levels of Ficolin-3 and Mannose-Binding Lectin in Patients with Leprosy and Their Family Contacts in a Hyperendemic Region in Northeastern Brazil.

The present study aimed at analyzing the serum levels of mannose-binding lectin (MBL) and ficolin-3 (FCN3) in leprosy patients and their healthy family contacts in a hyperendemic region in northeastern Brazil. A cross-sectional study was carried out with 90 patients who had been diagnosed with leprosy and 79 healthy family contacts. Serum levels of the MBL and FCN3 proteins were measured using the immunofluorometric assay (ELISA). Clinical information was determined from the patients’ charts. It was observed that the leprosy patients were more likely to be male (OR = 2.17; p = 0.01) and younger than fifteen years of age (OR = 2.01; p = 0.03) when compared to the family contacts. Those under 15 years of age had higher levels of MBL (4455 ng/mL) than those over 15 years of age (2342 ng/mL; p = 0.018). Higher FCN3 levels were identified in patients with indeterminate leprosy (41.9 µg/mL) compared to those with the lepromatous form (34.3 µg/mL; p = 0.033) and in those with no physical disabilities (38.1 µg/mL) compared to those with some disability (p = 0.031). Higher FCN3 levels were also observed in the group of patients without leprosy reactions (37.4 µg/mL) compared to those with type 1 (33.7 µg/mL) and type 2 (36.1 µg/mL) reactions. The MBL levels were higher in children under 15 years of age than they were in adults. It was evidenced that higher FCN3 serum levels were associated with early and transient clinical forms and lower expression in severe forms of leprosy.

Impact of mannose-binding lectin gene polymorphism on lung functions among workers exposed to airborne Aspergillus in a wastewater treatment plant in Egypt

In this study, the risk of Aspergillus (Asp.) positivity and its respiratory health impacts on wastewater treatment plant (WWTP) workers were studied. In addition, it identified the geno-susceptibility role of mannose-binding lectin 2 (MBL2) gene polymorphisms and the mannose-binding lectin (MBL) serum levels on the pulmonary functions of the Asp.-positive workers. Pulmonary function tests (PFTs) were performed for 89 workers from a selected WWTP, after exclusion of the smokers. Molecular identification of Asp. blood positivity was done by 18S rRNA sequencing. Determination of MBL2 gene polymorphism and estimation of MBL serum levels were done. PFTs revealed abnormalities in 49.2% of the workers. Asp. was positive in 42.5% of the workers with different species. Among the Asp.-positive workers, 6.5% of the workers were with obstructive PFTs, 12.9% with restriction, and 22.6% with combined PFT abnormalities. MBL2 genotyping showed that wild genotype AA was common (68.5%) among Asp.-positive workers compared to the other genotypes. This allele, whether homozygous or heterozygous, was significantly associated with decline in PFTs of the exposed workers. MBL serum levels were significantly lower in workers with obstructive, restrictive, and combined PFT abnormalities compared to those with normal PFTs, and in the workers with Asp.-positive species than the Asp.-negative workers. Moreover, it was significantly lower in workers with Asp. fumigatus compared to that in the workers with other Asp. species, and in the Asp.-positive workers with homozygous or heterozygous A allele compared to that in the Asp.-positive workers with homozygous B allele. Working in a WWTP can be associated with impaired PFTs due to exposure to airborne fungi. MBL2 genotyping showed that Asp.-positive workers with homozygous or heterozygous A allele were at risk to develop decline in their PFTs.

Association of serum mannose-binding lectin, anti-phospholipase A2 receptor antibody and renal outcomes in idiopathic membranous nephropathy and atypical membranous nephropathy: a single center retrospective cohort study

Objectives Idiopathic membranous nephropathy (iMN) is a major cause of nephrotic syndrome. Atypical membranous nephropathy (aMN) is a new type of nephropathy in China, characterized by a ‘full-house’ on immunofluorescent examination, that is IgG, IgA, IgM, C3, C1q positive, but without clinical evidence of a secondary cause. Phospholipase A2 receptor (PLA2R) was the major target antigens in iMN patients. Activation of the mannose-binding lectin (MBL) pathway plays a vital role in the development of MN. Our objective was to investigate the role of PLA2R and MBL in the pathogenesis of iMN and aMN. Methods We conducted a retrospective observational study using propensity score matching by age, gender, and eGFR. All clinical, laboratory data, and follow-up data of the patients were collected. Serum levels of anti-PLA2R antibodies and MBL were tested. Results Finally, 30 iMN patients and 30 aMN patients were included, and 20 healthy controls were retrospectively collected in this study. The 24 h proteinuria level was higher and serum albumin was lower in anti-PLA2R (+) patients than in anti-PLA2R (−) patients in both iMN and aMN groups. In aMN patients, MBL levels were significantly higher in anti-PLA2R (+) patients than in anti-PLA2R (−) patients (p = .045). The serum level of anti-PLA2R positively correlated with no-remission in both iMN and aMN groups. Conclusions The complement lectin pathway has an association with the development of MN, especially in patients with positive anti-PLA2R antibodies. Serum MBL cannot differentiate between the two diseases. Serum MBL levels are not associated with clinical manifestations, nor with prognosis.

Diversity of complement activation in different thyroid diseases

ObjectiveTo investigate complement components expression in both thyroid tissues and serum from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), and papillary thyroid cancer (PTC). MethodsC1q, mannose binding lectin (MBL), Bb, C4d, C3d and membrane attack complex (MAC) (C5b-9) deposition and complement regulate proteins (CD46, CD55 and CD59) expression in thyroid tissues from HT, GD, PTC, and control groups were examined by IHC. C1q, MBL, Bb, C4d, C3a, and soluble C5b-9 (sC5b-9) serum levels in the HT, GD, PTC, and healthy donor (HD) groups were measured by ELISAs. ResultsMAC deposition was detected in thyroid tissues in the HT, GD and PTC groups, but not the control group. MBL, Bb, C4d, C3d and MAC staining intensities in thyroid tissues were significantly higher in the HT and PTC groups than in the control group (all P < 0.05). The C1q level was higher in HT tissues than in control tissues (both P < 0.05). No complement component had a significant difference in staining intensities between the GD and control groups. CD55 and CD59 expression levels in thyroid tissues were higher in the PTC group than in the HT, GD and control groups (all P < 0.05). Similarly, CD46 levels were higher in HT tissues than in control tissues. Bb, C4d, C3a and sC5b-9 serum levels were significantly increased in HT, GD and PTC patients compared with HDs (all P < 0.05). ConclusionComplement is overactivated in HT and PTC, but not in GD. All the three pathways are activated in HT, and the MBL and alternative complement pathways are activated in PTC. These distinct complement activation profiles may participate in HT, GD and PTC pathogenesis.

Mannose-binding lectin activates the nuclear factor-κB and renal inflammation in the progression of diabetic nephropathy.

Increased serum mannose-binding lectin (MBL) level has been proven to correlate with the development of diabetic nephropathy (DN). Here, we aim to find the role and mechanism of MBL involved in the progression of DN. Patients with DN were recruited and divided into two groups according to different rs1800450genotypes of the MBL2gene, and inflammatory profiles in monocytes/macrophages were compared between the two groups. MBL was given to treat macrophages, HK2, and HMC, and a co-culture transwell system was then employed. Renal inflammation and fibrosis parameters were measured after knocking down or overexpressing MBL genes in mice. Proinflammatory profile, manifesting as enhanced IL-1β production and M1 polarization, was found in monocytes/macrophages from DN with a rs1800450 GG genotype of MBL2gene who had higher MBL level, compared with those with a rs1800450 GA genotype. In mechanism, MBL directly induced inflammatory responses in macrophages, which promoted inflammatory and fibrotic markers in HK2 and HMCs during co-culture. Further experiments showed that MBL can promote macrophages transforming to the M1subset mainly by activating the nuclear factor-κB pathway. After downregulation of MBL, the blood glucose, triglyceride, urine protein, injuries of glomerulus and tubules, and the degree of renal inflammation and fibrosis were ameliorated in db/db mice treated with AAV-MBL1/2-shRNA. Overexpression of MBL promoted macrophage infiltration in the kidney. In conclusion, MBL is a crucial mediator in the progression of DN via activating the nuclear factor-κB pathway in macrophages. This will serve as a genetic base for some patients with DN who have poor outcomes and provide a direction for the screening.

Mannose-binding lectin levels and MBL2 gene polymorphisms are associated with dengue infection in Brazilian children at the early ages

BackgroundThe mannose-binding lectin (MBL) plays an important role in innate immunity. Genetically determined variations in serum levels of MBL may influence the susceptibility and clinical outcome of dengue infection in early life. MethodsWe investigated the MBL2 gene polymorphisms and serum levels of MBL (total and functional) in children with asymptomatic (n=17) and symptomatic (n=29) primary dengue infections and age-matched uninfected children (n=84) enrolled in a birth cohort with dengue in Brazil. Polymorphisms of the MBL2 gene were assessed by reverse transcription-polymerase chain reaction (RT-PCR), whereas the enzyme-linked immunosorbent assay (ELISA) was used to quantify serum levels of MBL. ResultsWe found that the X allele and YX genotype in the MBL2 were more frequent in the dengue cases than in the control group. Likewise, the LXPA haplotype was exclusively found in dengue cases, thus probably related to dengue infection in our setting. Moreover, we found a higher frequency of the O allele and AO genotype in the control group. Serum levels of total and functional MBL were higher in dengue naïve infants than in dengue cases. ConclusionsMBL2 variants related to lower production of serum MBL were associated with dengue infection in infants, whereas intermediate to high levels of total and functional serum MBL were associated with protection against dengue infection. These findings highlight the role of MBL2 variants and serum levels of MBL in the susceptibility of children to dengue disease at early ages.