Mannose Binding Research Articles

Mast cell activation syndrome, Mannose binding lectin, Ehlers-Danlos syndrome, and Neuropsychiatric symptoms. (P17-1.004)

Mast cell activation syndrome, Mannose binding lectin, Ehlers-Danlos syndrome, and Neuropsychiatric symptoms. (P17-1.004)

LMAN1, a Negative Regulator of the Response to House Dust Mite

Abstract We have utilized an unbiased receptor capture approach (CaptiRec) to screen for receptors on dendritic cells which directly bind HDM. Using this technique, we have identified LMAN1 (Lectin, Mannose Binding 1) as a candidate receptor for HDM. LMAN1 is a mannose binding lectin which is primarily known to act as a cargo transporter between the ER, ERGIC, and Golgi compartments. The role played by LMAN1 in the recognition of and response to HDM, is currently unknown. We verify the ability of LMAN1 to directly bind HDM proteins biochemically and in a cellular context. Furthermore, we present evidence to demonstrate that LMAN1 downregulates NF-κB responses in response to inflammatory cytokines and to HDM. Loss of LMAN1 on DCs used for allergic sensitization leads to exacerbated airway inflammation in a HDM model of allergic asthma. Lastly, peripheral DCs of asthmatics show a significant reduction in expression of LMAN1 compared to healthy controls. These findings have potential implications for the development of novel therapeutic interventions for allergy and allergic asthma. Supported by American Lung Association Innovation Award IA-695632

The myrosinase-glucosinolate system to generate neoglycoproteins: A case study targeting mannose binding lectins

A convenient strategy for a ‘one-pot’ synthesis of neoglycoproteins (NGP) was developed using the myrosinase-glucosinolate couple, a natural enzyme-substrate system. This enzymatic reaction allowed us to generate an isothiocyanate in situ which then reacted with the lysine residues of bovine serum albumin protein (BSA) to produce multivalent neoglycoproteins. Using two models, glucomoringin which is a natural glucosinolate bearing a l-rhamnose unit, and an artificial glucosinolate specifically designed for mannose type lectins, an average of up to 17.8 and 28.7 carbohydrate residues could be respectively grafted onto the BSA protein. This process is comparable to commercial approaches using BSA-ManC without the disadvantage of handling harmful chemical reagents. Lectin binding screening (GLYcoPROFILE®) showed that among all NGPs synthesized, BSA-Man 16 gave similar and in some cases better affinities in comparison with commercial BSA-Manc towards various mannose-specific lectins.

A novel plant lectin, NTL-125, interferes with SARS-CoV-2 interaction with hACE2

COVID-19 caused by SARS-CoV-2 virus has had profound impact on the world in the past two years. Intense research is going on to find effective drugs to combat the disease. Over the past year several vaccines were approved for immunization. But SARS-CoV-2 being an RNA virus is continuously mutating to generate new variants, some of which develop features of immune escape. This raised serious doubts over the long-term efficacy of the vaccines. We have identified a unique mannose binding plant lectin from Narcissus tazetta bulb, NTL-125, which effectively inhibits SARS-CoV-2 replication in Vero-E6 cell line. In silico docking studies revealed that NTL-125 has strong affinity to viral Spike RBD protein, preventing it from attaching to hACE2 receptor, the gateway to cellular entry. Binding analyses revealed that all the mutant variants of Spike protein also have stronger affinity for NTL-125 than hACE2. The unique α-helical tail of NTL-125 plays most important role in binding to RBD of Spike. NTL-125 also interacts effectively with some glycan moieties of S-protein in addition to amino acid residues adding to the binding strength. Thus, NTL-125 is a highly potential antiviral compound of natural origin against SARS-CoV-2 and may serve as an important therapeutic for management of COVID-19.

Serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine in lung transplant recipients

Lung transplant recipients have an increased risk for severe coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A third dose of a SARS-CoV-2 vaccine has been recommended for all solid organ transplant recipients, but data from lung transplant recipients specifically are scarce. In this study, the serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine was measured in 78 lung transplant recipients. Sixty-two percent (n = 48) had a serological response to vaccination, which was significantly higher than after the second vaccine dose (27 patients (35%); p = 0.0013). A positive serologic response was associated with having had COVID-19 (p = 0.01), and higher serum IgG level and complement mannose binding lectin pathway activity prior to vaccination (p = 0.04 and p = 0.03, respectively). Serologic response was not associated with the dose of mycophenolate mofetil or prednisone or other immune status parameters. Eleven patients (14%) developed COVID-19 after the second or third vaccine dose, but this did not associate with serologic response after the second vaccine dose (9% in patients who developed COVID-19 versus 39% in patients who did not develop COVID-19 (p = 0.09)), or with serologic response above cut-off values associated with clinical protection in previous studies. In conclusion, the response to mRNA-based SARS-CoV-2 vaccines in lung transplant recipients improves significantly after a third vaccine dose. Factors associated with a positive serologic response are having had COVID-19 prior to vaccination, and serum IgG and complement mannose binding lectin pathway activity prior to vaccination. Serologic response did not associate with clinical protection against COVID-19 in this study.

Mannose binding lectin defects and autoimmune diseases

Mannose binding lectin defects and autoimmune diseases

GRP75 as a functional element of cholix transcytosis

ABSTRACT Cholix (Chx) is secreted by non-pandemic strains of Vibrio cholerae in the intestinal lumen. For this exotoxin to induce cell death in non-polarized cells in the intestinal lamina propria, it must traverse the epithelium in the fully intact form. We identified host cell elements in polarized enterocytes associated with Chx endocytosis and apical to basal (A→B) vesicular transcytosis. This pathway overcomes endogenous mechanisms of apical vesicle recycling and lysosomal targeting by interacting with several host cell proteins that include the 75 kDa glucose-regulated protein (GRP75). Apical endocytosis of Chx appears to involve the single membrane spanning protein TMEM132A, and interaction with furin before it engages GRP75 in apical vesicular structures. Sorting within these apical vesicles results in Chx being trafficked to the basal region of cells in association with the Lectin, Mannose Binding 1 protein LMAN1. In this location, Chx interacts with the basement membrane-specific heparan sulfate proteoglycan perlecan in recycling endosomes prior to its release from this basal vesicular compartment to enter the underlying lamina propria. While the furin and LMAN1 elements of this Chx transcytosis pathway undergo cellular redistribution that are reflective of the polarity shifts noted for coatamer complexes COPI and COPII, GRP75 and perlecan fail to show these dramatic rearrangements. Together, these data define essential steps in the A→B transcytosis pathway accessed by Chx to reach the intestinal lamina propria where it can engage and intoxicate certain non-polarized cells.

New nanostructures inhibiting human mannose binding lectin identified by a novel surface plasmon resonance assay

Circulating mannose-binding lectin (MBL) plays an important role in the progression of tissue damage caused by ischemic events, an account of its high-affinity, multivalent binding to carbohydrate arrays exposed on damaged endothelium (damage-associated molecular patterns, DAMPS). MBL inhibitors have therefore been proposed as a novel protective therapeutic strategy to prevent secondary injury.We developed a new, convenient, robust surface plasmon resonance (SPR) assay for in vitro screening of compounds interfering with the binding of native human MBL to an appropriate chip surface functionalized with a pattern of sugar moieties mimicking DAMPS. We also characterized the procedure to regenerate the chip surface after each experimental session, accomplished by sequential cleaning with piranha solution followed by UV exposure. The SPR assay detects the specific binding of human recombinant MBL and native MBL present in human serum, and can identify inhibitors of this binding. We observed inhibitory effects of mannose (IC50 ≅ 5 mM), of a nine mannose residues carrying glycan (IC50 ≅ 0.33 mg/mL, corresponding to ~ 175 μM), and mainly mannose-coated gold nanoparticles (IC50 ≅ 1.1 μg /mL). These in vitro results serve as a basis for testing the protective properties of these molecules/nanoparticles later inthe more expensive and time-consuming studies in cells and animal models of MBL mediated-injuries.

FimH confers mannose-targeting ability to Bacillus Calmette-Guerin for improved immunotherapy in bladder cancer

BackgroundBladder cancer is a common disease worldwide with most patients presenting with the non-muscle-invasive form (NMIBC) at initial diagnosis. Postoperational intravesical instillation of BCG is carried out for patients with...

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.

Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response

There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1β and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.

Fasciola hepatica is refractory to complement killing by preventing attachment of mannose binding lectin (MBL) and inhibiting MBL-associated serine proteases (MASPs) with serpins.

The complement system is a first-line innate host immune defence against invading pathogens. It is activated via three pathways, termed Classical, Lectin and Alternative, which are mediated by antibodies, carbohydrate arrays or microbial liposaccharides, respectively. The three complement pathways converge in the formation of C3-convertase followed by the assembly of a lethal pore-like structure, the membrane attack complex (MAC), on the pathogen surface. We found that the infectious stage of the helminth parasite Fasciola hepatica, the newly excysted juvenile (NEJ), is resistant to the damaging effects of complement. Despite being coated with mannosylated proteins, the main initiator of the Lectin pathway, the mannose binding lectin (MBL), does not bind to the surface of live NEJ. In addition, we found that recombinantly expressed serine protease inhibitors secreted by NEJ (rFhSrp1 and rFhSrp2) selectively prevent activation of the complement via the Lectin pathway. Our experiments demonstrate that rFhSrp1 and rFhSrp2 inhibit native and recombinant MBL-associated serine proteases (MASPs), impairing the primary step that mediates C3b and C4b deposition on the NEJ surface. Indeed, immunofluorescence studies show that MBL, C3b, C4b or MAC are not deposited on the surface of NEJ incubated in normal human serum. Taken together, our findings uncover new means by which a helminth parasite prevents the activation of the Lectin complement pathway to become refractory to killing via this host response, in spite of presenting an assortment of glycans on their surface.

Scavenging of bacteria or bacterial products by magnetic particles functionalized with a broad-spectrum pathogen recognition receptor motif offers diagnostic and therapeutic applications

Sepsis is a dysregulated host response of severe bloodstream infections, and given its frequency of occurrence and high mortality rate, therapeutic improvements are imperative. A reliable biomimetic strategy for the targeting and separation of bacterial pathogens in bloodstream infections involves the use of the broad-spectrum binding motif of human GP-340, a pattern-recognition receptor of the scavenger receptor cysteine rich (SRCR) superfamily that is expressed on epithelial surfaces but not found in blood. Here we show that these peptides, when conjugated to superparamagnetic iron oxide nanoparticles (SPIONs), can separate various bacterial endotoxins and intact microbes (E. coli, S. aureus, P. aeruginosa and S. marcescens) with high efficiency, especially at low and thus clinically relevant concentrations. This is accompanied by a subsequent strong depletion in cytokine release (TNF, IL-6, IL-1β, Il-10 and IFN-γ), which could have a direct therapeutic impact since escalating immune responses complicates severe bloodstream infections and sepsis courses. SPIONs are coated with aminoalkylsilane and capture peptides are orthogonally ligated to this surface. The particles behave fully cyto- and hemocompatible and do not interfere with host structures. Thus, this approach additionally aims to dramatically reduce diagnostic times for patients with suspected bloodstream infections and accelerate targeted antibiotic therapy. Statement of significanceSepsis is often associated with excessive release of cytokines. This aspect and slow diagnostic procedures are the major therapeutic obstacles. The use of magnetic particles conjugated with small peptides derived from the binding motif of a broad-spectrum mucosal pathogen recognition protein GP-340 provides a highly efficient scavenging platform. These peptides are not found in blood and therefore are not subject to inhibitory mechanisms like in other concepts (mannose binding lectine, aptamers, antibodies). In this work, data are shown on the broad bacterial binding spectrum, highly efficient toxin depletion, which directly reduces the release of cytokines. Host cells are not affected and antibiotics not adsorbed. The particle bound microbes can be recultured without restriction and thus be used directly for diagnostics.

Conserved FimH mutations in the global Escherichia coli ST131 multi-drug resistant lineage weaken interdomain interactions and alter adhesin function

The binding of the type 1 fimbrial adhesin FimH to mannosylated receptors is allosterically regulated to enhance the fitness of uropathogenic Escherichia coli (UPEC) during urinary tract infection (UTI). Mutations in the two FimH domains (pilin and lectin) located outside the mannose binding pocket have been shown to influence mannose binding affinity, yet the details of the allostery mechanism are not fully elucidated. Here we characterised different FimH conformational states (termed low-affinity tense and high-affinity relaxed conformations) of natural FimH variants using molecular dynamics (MD) simulation techniques and report key structural dynamics differences between them. The clinically dominant FimH30 variant from the pandemic multidrug resistant E. coli ST131 lineage contains an R166H mutation that weakens FimH interdomain interactions and allows enhanced mannose interactions with pre-existing high-affinity relaxed conformations. When expressed in an isogenic ST131 strain background, FimH30 mediated high human cell adhesion and invasion, and enhanced biofilm formation over other variants. Collectively, our computational and experimental findings support a model of FimH protein allostery that is mediated by shifts in the pre-existing conformational equilibrium of FimH, additional to the sequential step-wise process of structural perturbations transmitted from one site to another within the protein. Importantly, it is the first study to shed light into how natural mutations in a clinically dominant FimH variant influence the protein’s conformational landscape optimising its function for ST131 fitness at intestinal and extraintestinal niches.

Targeting cell surface glycans with lectin-coated fluorescent nanodiamonds.

Glycosylation is arguably the most important functional post-translational modification in brain cells and abnormal cell surface glycan expression has been associated with neurological diseases and brain cancers. In this study we developed a novel method for uptake of fluorescent nanodiamonds (FND), carbon-based nanoparticles with low toxicity and easily modifiable surfaces, into brain cell subtypes by targeting their glycan receptors with carbohydrate-binding lectins. Lectins facilitated uptake of 120 nm FND with nitrogen-vacancy centers in three types of brain cells – U87-MG astrocytes, PC12 neurons and BV-2 microglia cells. The nanodiamond/lectin complexes used in this study target glycans that have been described to be altered in brain diseases including sialic acid glycans via wheat (Triticum aestivum) germ agglutinin (WGA), high mannose glycans via tomato (Lycopersicon esculentum) lectin (TL) and core fucosylated glycans via Aleuria aurantia lectin (AAL). The lectin conjugated nanodiamonds were taken up differently by the various brain cell types with fucose binding AAL/FNDs taken up preferentially by glioblastoma phenotype astrocyte cells (U87-MG), sialic acid binding WGA/FNDs by neuronal phenotype cells (PC12) and high mannose binding TL/FNDs by microglial cells (BV-2). With increasing recognition of glycans having a role in many diseases, the lectin bioconjugated nanodiamonds developed here are well suited for further investigation into theranostic applications.

Toll-Like Receptors and Mannose Binding Lectin Gene Polymorphisms Associated with Cryptosporidial Diarrhea in Children in Southern India.

ABSTRACT.In low-resource settings, Cryptosporidium spp. is a common cause of diarrheal disease in children under the age of 3 years. In addition to diarrhea, these children also experience subclinical episodes that have been shown to affect growth and cognitive function. In this study, we screened polymorphisms in the promoter and exon1 regions of the mannose binding lectin 2 (MBL2) gene, as well as single nucleotide polymorphisms (SNPs) described in toll-like receptors (TLR) TLR1, TLR2, TLR4, and TLR9 and TIR domain-containing adaptor protein (TIRAP) genes among children with cryptosporidial diarrhea (cases) and children who only experienced asymptomatic (subclinical) cryptosporidiosis (controls). Among the polymorphisms screened, the variant allele B at codon 54 (rs1800450) of the MBL2 gene was associated with susceptibility to cryptosporidial diarrhea (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.1–4.5). When plasma MBL levels were compared, 72% of cases were found to be deficient compared with 32% among controls (OR = 5.09). Among TLR polymorphisms screened, multivariate analysis showed that heterozygous genotypes of TLR4 896A/G (rs4986790, OR = 0.33, 95% CI: 0.11–0.98) and TIRAP 539 C/T (rs8177374, OR = 0.19, 95% CI: 0.06–0.64) SNPs were associated with protection from cryptosporidial diarrhea. Although not statistically significant, these findings suggest that polymorphisms of MBL2 and TLR genes influence susceptibility to symptomatic cryptosporidial diarrhea even in settings with high exposure levels. Further studies to validate these findings in a larger cohort and to understand the role of these polymorphisms in mediating innate and adaptive immune responses to cryptosporidial infection are necessary.

A platform for specific and sensitive detection of target bacteria by selective magnetic enrichment and a broad-spectrum fluorescent probe

The indiscriminate application of antibiotics has led to the spread of antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae carbapenemase 2-expressing Klebsiella pneumoniae (KPC-2 KP), resulting in a global threat to public health. A method for specific, sensitive, and rapid detection of such bacteria is essential for clinical diagnosis and treatment. In this study, target bacteria were selectively captured using aptamer-coated magnetic beads (Apt-MBs), followed by recognition and detection by a broad-spectrum fluorescent probe, fragment crystallizable mannose binding lectin-coated gold nanoclusters (FcMBL@AuNCs). As a proof of concept study, a Gram-positive bacterium (i.e., MRSA) and Gram-negative bacterium (i.e., KPC-2 KP) were selected as models and detected by the proposed strategy. The determination of MRSA and KPC-2 KP was in the range of 20–108 CFU/mL with a detection limit (DL) of ~20 CFU/mL. Furthermore, the method shows great specificity for target bacteria, and detection procedures could be completed in 15 min. With these priorities, this platform has been applied successfully to the detection of MRSA and KPC-2 KP in human urine, saliva, cerebrospinal fluid, and bovine blood. Utilizing different aptamers, this strategy could also be used to monitor other target bacteria with high specificity and sensitivity.

Evaluation of the serum levels of Mannose binding lectin‐2, tenascin‐C, and total antioxidant capacity in patients with coronary artery disease

BackgroundCoronary artery disease (CAD) develops as a result of atherosclerosis. Atherosclerosis is a condition that leads to clogged arteries and can be caused by a variety of factors. Several studies have shown that various factors contribute to the development and progression of CAD. The aim of this study was to investigate the serum levels of MBL‐2, TNC and TAC in patients with CAD and the relationship between these biochemical parameters and the progression of CAD.MethodsIn this study, 60 serum samples were obtained from CAD patients as the case group and 20 healthy serum samples as the control group. Serum levels of MBL‐2 and TNC were measured by the ELISA method. Serum TAC level was determined by calorimetry (spectrophotometry). In addition, MDA serum level was measured by reaction with thiobarbituric acid (TBA).ResultsThe mean age in the case and control groups was 58.4 ± 9.5 years and 85 ± 9.8 years, respectively. There was no significant difference in age, sex and family history in patients with CAD (p > 0.05), but there was a significant difference in blood pressure and smoking history (p > 0.05). Serum cholesterol, triglyceride, and LDL levels were significantly increased in the case group compared to the control group, while serum HDL‐C levels were significantly decreased in the case group. Serum levels of MBL‐2, TNC, and MDA were significantly increased in the case group compared to the control group. The serum level of TAC was significantly lower in the case group than in the control group.ConclusionThis study suggests that it is possible to diagnose patients with coronary artery disease (CAD) in the early stages of their disease and take preventive measures by measuring these parameters in serum. However, more research is needed before these serum parameters can be considered diagnostic biomarkers or therapeutic targets.

Effects of dietary short‐chain fatty acid salts on the growth performance, digestive, antioxidant and immune enzyme activities, immune‐related gene expression and resistance to Vibro parahaemolytics infection in juvenile ridgetail white prawn ( Exopalaemon carinicauda )

An 8-week feeding trial was conducted to study the effects of dietary short-chain fatty acid salts, sodium acetate (SA), sodium propionate (SP) and sodium butyrate (SB), on the growth performance, digestive ability, immune parameters and disease resistance of juvenile Exopalaemon carinicauda. Shrimps (14.60 ± 1.48 mg) were fed with 10 experimental diets containing 0.0 (control), 0.25%, 0.5% and 1% of SA, SB and SP in triplicate. The highest survival rate was observed in the SP (0.5%) group (p < 0.05). The final weight, specific growth rate and feed efficiency was highest in the SP (0.25%) group (p < 0.05). Shrimps that were fed SP (0.25%) had greater intestinal digestive enzyme (chymotrypsin) activity. Shrimps in the SA (0.5%) group had the highest activities of glutathione peroxidase, catalase, lysozyme, acid phosphatase and alkaline phosphatase, which was accompanied by the highest relative percent survival after a Vibro parahaemolyticus challenge (p < 0.05). The expression of immune-related genes (prophenoloxidase, C-type lectin and mannose binding lectin) in the hepatopancreas of shrimps fed SA (0.5%) and SP (0.25%) was higher than that of the control group (p < 0.05). These data suggest that SA (0.5%) and SP (0.25%) are beneficial to the growth performance and health of E. carinicauda.

Effect of Clinical, Biochemical, and Genetic Variations on Medical Management in Filarial Chyluria: A Prospective Study at a Tertiary Care Centre in North India.

ObjectiveTo analyze the effect of clinical, biochemical factors, and Mannose Binding Lectin 2 (MBL2) gene variations on medical management in filarial chyluria (FC) patients.Material and methodsWe conducted a study between March 2013 and April 2016. MBL2polymorphisms were genotyped in confirmed 101 medically-treated cases of FC. Demographic, clinical, and biochemical variables were compared between remission and failure groups. Genotyping of MBL2 codon 54 and promoter -221 were undertaken by polymerase chain reaction. Genotype frequencies were compared with clinical and biochemical variables and medical treatment outcomes (remission/failure). The association between genotypes and treatment response was estimated by OR and 95% CI and generated by the chi-square test.ResultsThe mean age was 36.9±10.28-years and the male-female ratio was 3:1.2. Sixty-six patients had remission (Group-A) while 35 had recurrence (Group-B) at a mean follow-up of 21 months. The success rate for medical therapy was 65.35%. There was no statistical difference observed in the demographic profile of the two groups. On multivariate analysis, patients in Group-B had a higher grade of chyluria (p=0.005), had experienced greater number of disease attacks in the past (p=0.022), and had higher urinary triglyceride levels (TG) (p<0.001) as compared to Group-A patients. A significant association of MBL2 codon 54 genotypes was observed with the recurrent presentation of chyluria (p=0.044), grade of chyluria (p=0.028), and urinary TGs (p=0.001). However, genotype distribution at -221 did not show association with clinical and biochemical parameters of FC patients. The distribution of genotypes at codon 54 differed significantly between remission and failure/recurrence group; the variant genotype BB was significantly higher in the recurrence or failure group (OR:6.00; 95%CI, 1.00-35.91; p=0.050). However, frequencies of variant genotype YX and recessive group YX+XX of MBL2 -221 promoter was higher in remission group (OR:2.97;95%CI, 1.23-7.13; p=0.018 and OR:2.76; 95%CI, 1.80-6.50; p=0.020), respectively, showing that genetic variant may be associated with response to medical therapy.ConclusionHigher grade of chyluria, a higher number of disease attacks in the past, and higher urinary TGs levels were clinical predictors of poor response to medical treatment. Our results showed that the variants of MBL2 genes have an impact on treatment outcomes in FC patients. These observations may be limited by sample size.