Serum Mannose-binding Lectin Research Articles

Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus aureus Bacteremia

ObjectivesMannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients.MethodsWe conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia (≥7 days) and 46 patients with resolving bacteremia (<3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people.ResultsPatients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (P = 0.019 and P = 0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83–196.37; P = 0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19–29.57; P = 0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12–63.39; P = 0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03–4.26; P = 0.040).ConclusionsThis is the first demonstration of an association of low MBL levels and MBL2 polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB.

Association of levels of mannose-binding lectin and the MBL2 gene with type 2 diabetes and diabetic nephropathy.

ObjectiveTo investigate the association of Mannose-binding lectin (MBL) and the MBL2 gene with type 2 diabetes and diabetic nephropathy and the influence of MBL2 polymorphisms on serum MBL levels.MethodsThe study population included 675 type 2 diabetic patients with or without nephropathy and 855 normoglycemic controls. The single nucleotide polymorphisms (SNPs) of rs1800450, rs1800451, and rs11003125 of the MBL2 gene were determined by the Multiplex Snapshot method. Serum MBL levels were measured by enzyme-linked immune sorbent assay.ResultsRs1800450 and rs11003125 SNPs demonstrated strong linkage disequilibrium in the study population (r2 = 0.97). The haplotypes constructed from the G allele of rs1800450 and the C allele of rs11003125 increased the risk for type 2 diabetes (OR = 1.2, 95% CI = 1.1–1.4, P = 0.01). For rs1800450, GG and GA genotypes were associated with type 2 diabetes (P = 0.02, 0.01, respectively). For rs11003125, the GC genotype frequency was significantly different between patients and controls (18.1% vs. 24.9%, P = 0.001). Analyses of genotypes and allele frequency distributions among patients with normal UAE, microalbuminuria, and macroalbuminuria showed that there was no obvious evidence of association between the MBL2 gene and diabetic nephropathy. Subjects with the GG genotype of rs1800450 and the CC genotype of rs11003125 had much higher serum MBL levels.ConclusionsThe rs1800450 and rs11003125 SNPs of the MBL2 gene have strong linkage disequilibrium and are associated with type 2 diabetes in the North Chinese Han population. No association was observed between the MBL2 gene and diabetic nephropathy. Subjects with the GG genotype of rs1800450 and the CC genotype of rs11003125 had much higher serum MBL levels. An association between elevated serum MBL and diabetic nephropathy was also observed.

The Relationship Between Serum Mannose-Binding Lectin Levels and Acute Ischemic Stroke Risk

Complement activation and inflammation have been suggested in the pathogenesis of stroke, mannose-binding lectin (MBL) were found to have roles during the process. The aim of this study was to investigate the relationship between acute ischemic stroke (AIS) and serum MBL levels in Chinese population. From January 1 to June 30 2013, all patients with first-ever AIS were recruited to participate in the study. Serum MBL levels and routine test were examined. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to MBL levels. During the inclusion period, 148 patients with AIS were registered and completed study. The results indicated that the serum MBL levels were significantly (p<0.0001) higher in acutely ischemic stroke patients as compared to normal controls [1,332; interquartile range (IQR) 996-2,134μg/L and 897; IQR 678-1,100μg/L, respectively]. There was a correlation between serum levels of MBL and NIHSS score [r (spearman)=0.608, p<0.0001). In multivariate analysis, serum MBL as a continuous variable was associated with an increased risk of AIS, after adjustment for above possible confounders (OR 1.002, 95% CI 1.001-1.008; p<0.0001). These results indicated that elevated MBL levels could be considered as an independent stroke risk factor in Chinese population, suggesting a role of MBL and the lectin pathway of complement activation in the pathogenesis of stroke.

Adjuvant effects of mannose-binding lectin ligands on the immune response to infectious bronchitis vaccine in chickens with high or low serum mannose-binding lectin concentrations

Mannose-binding lectin (MBL) plays a major role in the immune response as a soluble pattern-recognition receptor. MBL deficiency and susceptibility to different types of infections have been subject to extensive studies over the last decades. In humans and chickens, several studies have shown that MBL participates in the protection of hosts against virus infections. Infectious bronchitis (IB) is a highly contagious disease of economic importance in the poultry industry caused by the coronavirus infectious bronchitis virus (IBV). MBL has earlier been described to play a potential role in the pathogenesis of IBV infection and the production of IBV-specific antibodies, which may be exploited in optimising IBV vaccine strategies. The present study shows that MBL has the capability to bind to IBV in vitro. Chickens from two inbred lines (L10H and L10L) selected for high or low MBL serum concentrations, respectively, were vaccinated against IBV with or without the addition of the MBL ligands mannan, chitosan and fructooligosaccharide (FOS). The addition of MBL ligands to the IBV vaccine, especially FOS, enhanced the production of IBV-specific IgG antibody production in L10H chickens, but not L10L chickens after the second vaccination. The addition of FOS to the vaccine also increased the number of circulating CD4+ cells in L10H chickens compared to L10L chickens. The L10H chickens as well as the L10L chickens also showed an increased number of CD4−CD8α−γδ T-cells when an MBL ligand was added to the vaccine, most pronouncedly after the first vaccination. As MBL ligands co-administered with IBV vaccine induced differences between the two chicken lines, these results indirectly suggest that MBL is involved in the immune response to IBV vaccination. Furthermore, the higher antibody response in L10H chickens receiving vaccine and FOS makes FOS a potential adjuvant candidate in an IBV vaccine.

Innate immunity in renal transplantation: The role of mannose-binding lectin

Innate immune system plays an important role in the modulation of the inflammatory response during infection and tissue injury/repair. Mannose-binding lectin (MBL) is a component of the innate immune system that activates complement via the lectin pathway. Different polymorphisms of the MBL gene are associated with MBL levels and MBL function. The relationship between MBL and disease is rather complex because MBL behaves as a double-edged sword. In the general population, low serum MBL levels are associated with higher risk of infection, type 2 diabetes, autoimmune and cardiovascular disease. However, in patients with diabetes or autoimmune disease, high MBL levels are associated with more severe renal and cardiovascular comorbidities. In renal transplantation, low MBL serum levels constitute a risk factor for infection, low grade inflammation, new onset diabetes after transplantation and subclinical rejection. Despite these associations suggest that low MBL levels should be associated with poorer renal allograft outcome, epidemiological studies evaluating the predictive value of MBL levels on graft survival are controversial. Taken together, these observations suggest that low MBL serum levels modulate chronic inflammatory response that may influence transplant outcome.

Characterization of mannose‐binding lectin (MBL) variants by allele‐specific sequencing of MBL2 and determination of serum MBL protein levels

Mannose-binding lectin (MBL) is a major component of the lectin pathway of complement activation. High and low MBL levels have been associated with susceptibility and severity of a variety of infectious and autoimmune diseases. Several single-nucleotide polymorphisms (SNPs) in the promoter region and exon 1 of the MBL2 gene are responsible for variations in serum MBL levels. We developed a sequence-based typing method for allele-specific MBL2 genotyping and measured serum MBL protein levels in 24 German blood donors. We identified the common MBL2 haplotypes including five promoter polymorphisms in linkage with the Q allele and correlated serum MBL levels with the respective genotypes. The genotyping method presented here could provide a basis for confirmatory studies in larger cohorts.

Glycoepitopes of Staphylococcal Wall Teichoic Acid Govern Complement-mediated Opsonophagocytosis via Human Serum Antibody and Mannose-binding Lectin

Serum antibodies and mannose-binding lectin (MBL) are important host defense factors for host adaptive and innate immunity, respectively. Antibodies and MBL also initiate the classical and lectin complement pathways, respectively, leading to opsonophagocytosis. We have shown previously that Staphylococcus aureus wall teichoic acid (WTA), a cell wall glycopolymer consisting of ribitol phosphate substituted with α- or β-O-N-acetyl-d-glucosamine (GlcNAc) and d-alanine, is recognized by MBL and serum anti-WTA IgG. However, the exact antigenic determinants to which anti-WTA antibodies or MBL bind have not been determined. To answer this question, several S. aureus mutants, such as α-GlcNAc glycosyltransferase-deficient S. aureus ΔtarM, β-GlcNAc glycosyltransferase-deficient ΔtarS, and ΔtarMS double mutant cells, were prepared from a laboratory and a community-associated methicillin-resistant S. aureus strain. Here, we describe the unexpected finding that β-GlcNAc WTA-deficient ΔtarS mutant cells (which have intact α-GlcNAc) escape from anti-WTA antibody-mediated opsonophagocytosis, whereas α-GlcNAc WTA-deficient ΔtarM mutant cells (which have intact β-GlcNAc) are efficiently engulfed by human leukocytes via anti-WTA IgG. Likewise, MBL binding in S. aureus cells was lost in the ΔtarMS double mutant but not in either single mutant. When we determined the serum concentrations of the anti-α- or anti-β-GlcNAc-specific WTA IgGs, anti-β-GlcNAc WTA-IgG was dominant in pooled human IgG fractions and in the intact sera of healthy adults and infants. These data demonstrate the importance of the WTA sugar conformation for human innate and adaptive immunity against S. aureus infection.

Human SAP Is a Novel Peptidoglycan Recognition Protein That Induces Complement-Independent Phagocytosis of Staphylococcus aureus

The human pathogen Staphylococcus aureus is responsible for many community-acquired and hospital-associated infections and is associated with high mortality. Concern over the emergence of multidrug-resistant strains has renewed interest in the elucidation of host mechanisms that defend against S. aureus infection. We recently demonstrated that human serum mannose-binding lectin binds to S. aureus wall teichoic acid (WTA), a cell wall glycopolymer--a discovery that prompted further screening to identify additional serum proteins that recognize S. aureus cell wall components. In this report, we incubated human serum with 10 different S. aureus mutants and determined that serum amyloid P component (SAP) bound specifically to a WTA-deficient S. aureus ΔtagO mutant, but not to tagO-complemented, WTA-expressing cells. Biochemical characterization revealed that SAP recognizes bacterial peptidoglycan as a ligand and that WTA inhibits this interaction. Although SAP binding to peptidoglycan was not observed to induce complement activation, SAP-bound ΔtagO cells were phagocytosed by human polymorphonuclear leukocytes in an FcγR-dependent manner. These results indicate that SAP functions as a host defense factor, similar to other peptidoglycan recognition proteins and nucleotide-binding oligomerization domain-like receptors.

Unique variation in genetic selection among Black North American women and its potential influence on pregnancy outcome

We hypothesize that variations in the frequency of genetic polymorphisms, reflecting ancestral differences in living conditions and exposure to microorganisms, increase susceptibility to adverse pregnancy outcome among present day Black North American women. Striking differences were observed in the frequency of genetic variants between Black and White or Hispanic women in 5 genes (IL1RN, MBL2, PPARA, ATG16L1, CIAS1) associated with inflammation and anti-microbial immunity. The CIAS1 and IL1RN polymorphisms were associated with altered interleukin-1β serum levels; the MBL2 polymorphism resulted in a decreased serum mannose-binding lectin concentration. Gene polymorphisms associated with an alteration in innate immunity were most frequent in Black women. This may reflect an evolutionary selection in response to an ancient environment containing a high multitude of microorganisms, and may increase susceptibility of Black women to infection-associated preterm birth in the current North American environment.

VariantMBL2genotypes producing low mannose-binding lectin may increase risk of Bacillus Calmette-Guerin osteitis in vaccinated newborns

The aim of this study was to evaluate whether mannose-binding lectin (MBL) plays a role in the development of osteitis after Bacillus Calmette-Guerin (BCG) vaccination as a newborn. Blood samples were obtained from 132 former BCG osteitis patients, now aged 21-49years, and analysed for MBL concentration and MBL2 genotype in a controlled setting. Variant genotypes in the MBL2 gene were more common in the former BCG osteitis patients (42.4%) than in the population controls (32.3%, p=0.033). However, MBL concentrations at the age of 21-49years were not lower in these patients than in the controls in the same age group. The variant MBL2 genotypes were associated with low serum MBL concentrations, and moreover, MBL concentration was not measurable in two of those three patients who were homozygous for the variant MBL2 genotype. Low serum MBL concentrations were not associated with any illnesses in the medical history of the BCG patients, their siblings or children. Preliminary evidence was found that variant, low-MBL-producing genotypes may be associated with the increased risk of BCG osteitis in vaccinated newborns.

Mannose-binding lectin 2 gene polymorphisms affect serum mannose-binding lectin levels in adult asthmatics

Asthma is a chronic inflammatory disease of the airway characterized by airway hyperresponsiveness, tissue remodeling, and infiltration of immune cells. Although the pathophysiological mechanisms of airway inflammation are not fully understood, significant roles have been described for the complement activation byproducts C3a and C5a anaphylatoxins. It was suggested that generation of C3/C3a contributes to the development of common allergic pathways that enhance airway hyperresponsiveness, eosinophil infiltration, and Th2 cytokine production. [1] Zhang X. Köhl J. A complex role for complement in allergic asthma. Expert Rev Clin Immunol. 2010; 6: 269-277 Crossref PubMed Scopus (63) Google Scholar Conversely, ablation of the C5a and its receptor signaling results in the loss of dendritic cell modulation, which induces dysregulation of Th2-biased immune responses. [1] Zhang X. Köhl J. A complex role for complement in allergic asthma. Expert Rev Clin Immunol. 2010; 6: 269-277 Crossref PubMed Scopus (63) Google Scholar

Impaired thymic function and CD4 + T lymphopenia, but not mannose-binding lectin deficiency, are risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients

Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in kidney transplant recipients (KTR), but risk factors remain poorly defined. CD4+ T lymphopenia and mannose-binding lectin (MBL) deficiency are common immunodeficiencies in KTR. Here, we investigated whether CD4+ T lymphopenia and/or MBL deficiency would be risk factors for PCP in KTR. Furthermore, the role of thymic function in CD4+ T lymphopenia and outcome was studied by assessing CD45RA+CD31+CD4+ T cell numbers (RTE, recent thymus emigrants).In 321 de novo KTR serial determinations of peripheral T lymphocyte subsets (n=281, mean 4.2 times between days 0–365) and/or MBL levels (n=112, mean 1.8 times between days 30–180) were performed. 22/321 patients developed a PCP episode on average at day 199 (107–398) post-Tx.Age correlated inversely with RTE, CD4+ and CD8+ T-cell counts until day 180 post-Tx. RTE correlated with CD4+ T-cell counts at all time-points pre- and post-Tx. PCP patients had more CMV infections (p=0.045) within the first 3months compared to controls. Importantly, PCP patients were older (p=0.008), and had lower RTE (p=0.046) pretransplant, and lower CD4+ T-cell counts pretransplant (p=0.017), at day 60 (p=0.032) and for the average of all post-Tx values (p=0.027) compared to controls. Though treatment with T-cell depleting antibodies was associated with consecutive CD4+ T lymphopenia in the whole cohort, the number of patients who received T-cell depleting antibodies was comparable between PCP and control patients (p=0.754). A multivariate stepwise logistic regression model identified only pretransplant CD4+ T-cell counts (OR 0.011, p=0.010) and acute rejection (OR 4.66, p=0.023) as predictors of PCP.In contrast, MBL levels and incidence of MBL deficiency (<500ng/ml) at days 30, 90 and 180 post-Tx were not different between PCP patients and controls.In conclusion, PCP risk was associated with higher age and related to both thymic functional impairment and long-lasting CD4+ T-lymphopenia that started already before transplantation. Despite frequent occurrences in KTR, low levels of serum MBL were not associated with increased risk for PCP. CD4+ T-cell counts and function should be addressed in prospective studies for more individualized approaches to PCP prophylaxis.

Mannose-Binding Lectin Blunts Macrophage Polarization and Ameliorates Lupus Nephritis

BackgroundDeficiency in clearance of self nuclear antigens, including DNA, is the hallmark of systemic lupus erythematosus (SLE), a chronic autoimmnue disease characterized by the production of various autoantibodies, immune complex deposition and severe organ damage. Our previous studies revealed that administration of syngeneic BALB/c mice with activated lymphocyte-derived DNA (ALD-DNA) could induce SLE disease. Mannose-binding lectin (MBL), a secreted pattern recognition receptor with binding activity to DNA, has been proved to be a modulator of inflammation, but whether MBL takes responsibility for DNA clearance, modulates the DNA-mediated immune responses, and is involved in the development of DNA-induced SLE disease remain poorly understood.Methodology/Principal FindingsThe levels of serum MBL significantly decreased in lupus mice induced by ALD-DNA and were negatively correlated with SLE disease. MBL blunted macrophage M2b polarization by inhibiting the MAPK and NF-κB signaling while enhancing the activation of CREB. Furthermore, MBL suppressed the ability of ALD-DNA–stimulated macrophages to polarize T cells toward Th1 cells and Th17 cells. Importantly, MBL supplement in vivo could ameliorate lupus nephritis.Conclusion/SignificanceThese results suggest MBL supplement could alleviate SLE disease and might imply a potential therapeutic strategy for DNA-induced SLE, which would further our understanding of the protective role of MBL in SLE disease.

Mannose binding lectin (mbl2) haplotype frequencies in solid organ transplant patients and correlation with MBL protein levels — Evaluation of complement-mediated effector pathway deficiency

Mannose-binding lectin (MBL) is a protein critical in activating complement. Patients with wild-type and variant mbl2 genotypes have high or low concentrations of MBL protein, which is known to increase susceptibility to transplant rejection or infection, respectively. Our objective was to determine mbl2 genotype frequencies in future solid organ transplant recipients in order to optimize their induction and maintenance immunosuppressive therapies, and to provide MBL reference data for this unique population. We genotyped 1687 patients, and concurrently measured protein in 807 of them, during 2010–2011. Frequencies of the structural allele SNPs in our population were similar to those of other studied populations; however, Black patients with the same intermediate and deficient mbl2 genotypes as Caucasians produced significantly lower levels of MBL protein; therefore, within this population more genotypes should be considered MBL-deficient. Overall, the most critical parameter in determining serum MBL protein concentration was genotype, which was independent of other factors including ethnicity, gender, or diseased native organ type.

Potential Role of Mannose-Binding Lectin in Intrauterine Transmission of Hepatitis B Virus

Intrauterine transmission of hepatitis B virus (HBV) is the main cause of the high prevalence of HBV in endemic areas; however, the mechanisms underlying intrauterine transmission of HBV remain unknown. To explore the role of mannose-binding lectin (MBL), a pattern recognition molecule of the innate immune system, in intrauterine transmission of HBV, we determined MBL levels using an enzyme-linked immunosorbent assay (ELISA) in cord serum of 7 intrauterine-infected neonates and 30 non-infected neonates born to HBV-positive mothers, and 30 control neonates born to HBV-negative mothers. We observed significant differences in cord serum MBL levels among the three groups (P < 0.001). Non-infected neonates had significantly higher MBL levels than controls (P < 0.001), and intrauterine-infected neonates had significantly lower serum MBL levels than non-infected neonates (P < 0.001). However, serum MBL levels were not significantly different between intrauterine-infected neonates and controls (P = 0.800). Our results indicate that maternal HBV infection induces an increase in fetal MBL levels and the absence of this increase is possibly associated with intrauterine transmission of HBV, suggesting that MBL plays a role in intrauterine transmission of HBV.

Specific Serum Ig Recognizing Staphylococcal Wall Teichoic Acid Induces Complement-Mediated Opsonophagocytosis against Staphylococcus aureus

Wall teichoic acid (WTA) of Staphylococcus aureus is a major cell envelope-associated glycopolymer that is a key molecule in promoting colonization during S. aureus infection. The complement system plays a key role in the opsonization and clearance of pathogens. We recently reported that S. aureus WTA functions as a ligand of human serum mannose-binding lectin (MBL), a recognition molecule of the lectin complement pathway. Intriguingly, serum MBL in adults does not bind to WTA because of an inhibitory effect of serum anti-WTA-IgG. In this study, serum anti-WTA-IgG was purified to homogeneity using a purified S. aureus WTA-coupled affinity column to examine the biological function of human anti-WTA-IgG. The purified anti-WTA-IgG contained the IgG2 subclass as a major component and specifically induced C4 and C3 deposition on the S. aureus surface in the anti-WTA-IgG-depleted serum, but not in C1q-deficient serum. Furthermore, the anti-WTA-IgG-dependent C3 deposition induced phagocytosis of S. aureus cells by human polymorphonuclear leukocytes. These results demonstrate that serum anti-WTA-IgG is a real trigger for the induction of classical complement-dependent opsonophagocytosis against S. aureus. Our results also support the fact that a lack of the lectin complement pathway in MBL-deficient adults is compensated by Ag-specific, Ab-mediated adaptive immunity.

Association between serum levels of MASP-2 and neutropenic febrile attacks in children with leukemia.

Infectious complications are a major etiology of morbidity and mortality in febrile neutropenic patients. Low serum mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) concentration may represent a risk factor for infection in leukemia patients receiving chemotherapy. This study evaluates the relationship between serum levels of MASP-2 with neutropenic febrile attacks in children with leukemia. This prospective cohort study conducted between 2009-2010, we measured baseline serum MASP-2 levels by enzyme-linked immunosorbent assay (ELISA) prior to chemotherapy in leukemia patients less than 14 years of age. The relationship of febrile neutropenia (FN) episodes and duration of hospitalization with MASP-2 concentration was analyzed. We evaluated 75 children [38 girls (51%), 37 boys (49%); mean age, 61.6 ± 43.7 months]. There were 8 (10.7%) children with MASP-2 deficiency (< 200 ng/mL). Mean MASP-2 was 673.2 ± 288.7 ng/mL (range: 116-1112). Eight patients had no FN episodes. Of the 129 FN episodes recorded, 19 (average 2.4 times) were from the MASP-2deficient group and 110 (average 1.6 times) were in the normal group. There was a significant difference between the mean MASP-2 concentration and FN episodes (P = 0.043). There was an inverse relationship between FN episodes (r = -0.332, P = 0.004) and the duration of hospitalization (r = -0.334, P = 0.005) with MASP-2 concentration. MASP-2 deficient patients were hospitalized longer than the normal group, which was strongly significant (P < 0.001). Our study confirmed the results of several previous studies. MASP-2 deficiency in leukemic children treated with chemotherapy was associated with an increased risk of FN episodes, prolonged cumulative duration of hospitalization, and intravenous antimicrobial therapy.

Association between mannose-binding lectin and the sensitivities of common infections in children

Objective To investigate the association between genetic polymorphisms and protein levels of mannose-binding lectin (MBL) and the sensitivities of common infections in a pediatric Han population lived in Zhejiang Province.Methods MBL genetic polymorphisms of patients and controls were detected by PCR-based sequencing.MBL protein levels were measured using MBL ELISA Kit.Results No mutations at positions +223 and +239 of the exon 1 were detected in either patients or controls.No mutation at position +4 of the promoter was detected in controls.The frequencies of the three genotypes HH,HL,and LL at position-550 of the promoter were different between patients and controls(P＜0.05).The frequencies of genotypes YA and XB relevant to MBL protein levels were also different between patients and controls(P＜0.05).Comparing the frequencies of genotypes YA and XB in separate infectious disease with controls,significant differences were found in the group of RRI and CMV infection.The distributions of serum MBL level frequencies in patients and controls were both characterized by skewed distributions.MBL levels of patients with CMV infection were lower than those of controls(P＜0.05).Inversely,MBL levels of patients with acute respiratory infection and localized abscess were higher than those of controls (P＜O.05).Conclusion Genetic polymorphism of MBL gene is seemed to be relative to the sensitivity of common infections in children. Key words: Mannose/mannan-binding lectin ; Genetic polymorphism ; Children ; Infection

MBL2 gene variation affecting serum MBL is associated with prosthetic joint infection in Czech patients after total joint arthroplasty

Prosthetic joint infection (PJI) is a serious complication of the total joint arthroplasty (TJA). Serum mannose-binding lectin (MBL), a pattern recognition receptor, is involved in antibacterial immune response. This study investigated whether functional variants of the MBL2 gene may be associated with the risk of PJI. MBL2 -550 (H/L, rs11003125), MBL2 -221 (Y/X, rs7096206) and MBL2 +54 (G/A, rs1800450) single nucleotide polymorphisms (SNP) were genotyped in 112 PJI patients and two control groups: 245 patients with aseptic TJA and 196 Czech population controls without TJA. Serum MBL concentration was assessed in PJI patients (n = 92) and aseptic TJA controls (n = 56). The distribution of MBL2 genotypes complied with the Hardy-Weinberg equilibrium in all investigated groups. Importantly, MBL2 -550 L allele (allelic frequency, 0.72) and LL genotype (genotype frequency, 0.51) were more frequent among PJI patients compared to aseptic TJA controls (L allele: 0.63, P = 0.016, P(c) = 0.048; LL genotype: 0.39, P = 0.037, P(c) > 0.05) and to Czech population controls (L allele: 0.61, P = 0.010, P(c) = 0.030; LL genotype: 0.35, P = 0.006, P(c) = 0.018), respectively. Regarding MBL protein, the MBL2 -550 L carriers presented with lower serum MBL concentrations than non-carriers (median; 593 vs 1876 ng/ml; P < 0.01). Similarly, the carriage of MBL2 -221 X and 54 A alleles was associated with lower serum MBL concentrations (P < 0.01). In conclusion, MBL2 -550 genetic variant(s) associated with low serum concentration of MBL protein can increase the risk of PJI.

A study on anti-mannose binding lectin (anti-MBL) antibodies and serum MBL levels in Indian systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by systemic inflammation and autoantibody production. Anti-mannose binding lectin (anti-MBL) autoantibodies have been studied in SLE for their possible effect on mannose binding lectin (MBL) levels and functional activity. This study aimed at the detection of anti-MBL autoantibodies in Indian SLE patients and evaluates their relationship with related immunological parameters. Two hundred diagnosed SLE patients from Western India were included in the study where 87 patients were lupus nephritis (LN) (43.5 %) and remaining (56.5 %) were non-LN. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Anti-MBL autoantibodies to IgG and IgM isotypes, anti-C1q autoantibodies, MBL levels and circulating immune complex levels were detected by ELISA. C3, C4 and CRP levels were detected by nephelometer. Anti-MBL autoantibodies were detected in 52 % SLE patients, where 55 % had IgG-anti-MBL, 33.8 % had IgM-anti-MBL and 11.3 % had both subclasses. Low MBL levels were present in 64.4 % anti-MBL positives as compared to 61.5 % in anti-MBL negatives. Among anti-MBL positives, 74 % had anti-C1q antibodies, whereas 41.7 % of anti-MBL negatives had anti-C1q autoantibodies (p = 3.45E06). An inverse correlation was observed between serum MBL and CIC levels. A statistically significant difference was noted between anti-MBL positives and anti-MBL negative patients with hsCRP levels (p = 0.002). Occurrence of infections was higher among anti-MBL positives (65 %) as compared to anti-MBL negatives (35 %). The difference between SLEDAI scores among anti-MBL-positive and anti-MBL-negative groups was statistically insignificant. Anti-MBL autoantibodies in SLE patients can influence functional activity of MBL and have a significant role in SLE disease pathogenesis.