Mannose-binding lectin (MBL) role in the carriage of oropharyngeal bacteria is not known. We investigated the association of smoking, MBL2 polymorphisms, and MBL concentrations with oropharyngeal carriage of respiratory bacteria in young men. Oropharyngeal specimens, MBL concentrations, and MBL2 gene polymorphisms were measured in 124 asthmatic and 394 nonasthmatic Finnish military recruits. The carriage rates of S. pneumoniae (p = 0.002), N. meningitidis (p = 0.005), and beta-hemolytic streptococci (p < 0.001) throughout the military service were significantly higher among smokers than in nonsmokers. An MBL level below the median proved to be a significant risk factor for the carriage of N. meningitidis (odds ratio [OR] = 1.9; 95% confidence interval [CI] 1.0-3.6) and beta-hemolytic streptococci (OR = 2.0; 95% CI 1.2-3.2) in the nonsmokers and a borderline significant risk factor for the carriage of S. pneumoniae (OR = 1.5; 95% CI 0.9-2.6), whereas low MBL levels producing MBL2 haplotypes (LXA/LXA, LXA/O, HYA/O, LYA/O, O/O) seemed to be associated with the carriage of N. meningitidis (OR = 1.8; 95% CI 1.0-3.4) and S. pneumoniae (OR = 1.6; 95% CI 0.9-2.7). Thus, MBL deficiency may predispose nonsmokers to oropharyngeal carriage of these bacteria. We hypothesize that the major factor contributing to elevated bacterial carriage in smokers might be increased bacterial adherence to epithelial cells, which obscures the effect of MBL.

The mannose-binding lectin (MBL) 2 gene has an important function in the innate immune response and activation of the third pathway of the complement system. Some studies have assessed the association of the MBL2 gene polymorphisms with cervicovaginal infections (CVI); however, there is no information about this association in Mexican women. This study aimed to determine the association between the MBL2 codons 54 and 57 gene polymorphisms with CVI in a sample of Mexican women. Through a cross-sectional study, blood samples and cervicovaginal cultures were obtain from 354 women. MBL2 genotyping was performed by real-time polymerase chain reaction with Taqman probes. Of the 354 women studied, 128 (36.2%) had CVI and 226 (63.8%) were healthy. The frequencies of the C and T variants in codon 54 in women with CVI were 83% and 17%, respectively; whereas the frequencies of these variants in healthy women were 82% and 18%, respectively. The frequencies of variants C/C, C/T, and T/T in women with CVI were 68%, 31%, and 1%, respectively; whereas the frequencies of these variants in healthy women were 68%, 29%, and 3%, respectively. With respect to codon 57, the frequencies of variants C and T were identical in women with CVI and in healthy women (97% and 3%, respectively). The frequencies of variants C/C, C/T, and T/T were identical in women with CVI and in healthy women (94%, 6%, and 0%, respectively). We conclude that MBL2 codons 54 and 57 gene polymorphisms do not associate with CVI in Mexican women.

BACKGROUND

Mannose-binding lectin gene 2 (MBL2) plays a very important role in the first line of host immune response in Down syndrome (DS). The importance of MBL2 gene polymorphisms in children with DS is unclear, and no research has addressed MBL2 gene polymorphisms in patients with DS. This is the first report describing an important association between MBL2 gene polymorphisms and infections in children with DS.

METHODS

We compared the frequency of single-nucleotide polymorphisms (SNPs) at two codons of the MBL2 gene in a cross sectional cohort of 166 children with DS and 229 controls. Polymorphisms at codons 54 (GGC→GAC) and 57 (GGA→GAA) in exon 1 of the MBL2 gene were typed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique using the restriction enzymes BshN1 (derivated from Bacillus sphaericus) and MboII (derivated from Moraxella bovis), respectively.

RESULTS

MBL2 codon 54 GA genotype frequency was found to be lower in patients with DS (22.9%) than those of healthy controls (35.8%), differences were statistically significant (OR = 0.532, 95% CI = 0.339-0.836, P = 0.008). On the other hand, codon 57 polymorphism in the MBL2 gene was detected in none of the DS patients, but only one person in the control group showed codon 57 GA genotype (OR = 1.004, 95% CI = 0.996-1.013, P = 1.000).

CONCLUSIONS

Our data provides an evidence for the first time that a homozygote or heterozygote for the variant, MBL2 alleles, is not associated with infections in patients with DS, and do not influence the incidence of infections.

The aim of this study was to determine whether the functional mannose-binding lectin (MBL2) exon 1 codon 54 polymorphism (rs1800450) confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted on the MBL2 codon 54 polymorphism across 21 comparative studies. Meta-analysis showed an association between the MBL2 codon 54 B allele and SLE in all study subjects [odds ratio (OR) = 1.298, 95% confidence interval (CI) = 1.154-1.459, P = 1.4 × 10(-5)]. Analysis after stratification by ethnicity indicated that the MBL2 codon 54 B allele is significantly associated with SLE in Europeans, Asian, and Africans (OR = 1.246, 95% CI = 1.062-1.462, P = 0.007; OR = 1.268, 95% CI = 1.049-1.532, P = 0.014; OR = 1.939, 95% CI = 1.269-2.962, P = 0.002, respectively). However, African Americans had a much lower prevalence of the T allele (5.8%) than any other populations studied, whereas Asians had the highest prevalence (16.2%). This meta-analysis confirms that the MBL2 codon 54 polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.

OBJECTIVE

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.

METHODS

Blood samples were obtained from 132 former BCG osteitis patients, now aged 21-49 years, and analysed for MBL concentration and MBL2 genotype in a controlled setting.

RESULTS

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 21-49 years 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.

CONCLUSIONS

Preliminary evidence was found that variant, low-MBL-producing genotypes may be associated with the increased risk of BCG osteitis in vaccinated newborns.

OBJECTIVE

The MBL2 gene is the major genetic determinant of mannose-binding lectin (MBL)-an acute phase reactant. Low MBL levels have been associated with adverse outcomes in preterm infants. The MBL2Gly54Asp missense variant causes autosomal dominant MBL deficiency. We tested the hypothesis that MBL2Gly54Asp is associated with worse neurodevelopmental outcomes after cardiac surgery in neonates.

METHODS

This is an analysis of a previously described cohort of patients with nonsyndromic congenital heart disease who underwent cardiac surgery with cardiopulmonary bypass before age 6 months (n = 295). Four-year neurodevelopment was assessed in 3 domains: Full-Scale Intellectual Quotient, the Visual Motor Integration development test, and the Child Behavior Checklist to assess behavior problems. The Child Behavior Checklist measured total behavior problems, pervasive developmental problems, and internalizing/externalizing problems. A multivariable linear regression model, adjusting for confounders, was fit.

RESULTS

MBL2Gly54Asp was associated with a significantly increased covariate-adjusted pervasive developmental problem score (β = 3.98; P = .0025). Sensitivity analyses of the interaction between age at first surgery and MBL genotype suggested effect modification for the patients with MBL2Gly54Asp (Pinteraction = .039), with the poorest neurodevelopment outcomes occurring in children who had surgery earlier in life.

CONCLUSIONS

We report the novel finding that carriers of MBL2Gly54Asp causing autosomal dominant MBL deficiency have increased childhood pervasive developmental problems after cardiac surgery, independent of other covariates. Sensitivity analyses suggest that this effect may be larger in children who underwent surgery at earlier ages. These data support the role of nonsyndromic genetic variation in determining postsurgical neurodevelopment-related outcomes in children with congenital heart disease.

OBJECTIVE

Recently we found that the incidence of restenosis after carotid endarterectomy was significantly higher in patients homozygous for the normal genotype of mannose-binding lectin (MBL2) than in with patients with MBL2 variant genotypes. Several growth factors are also known to contribute to restenosis. Therefore, we investigated whether early postoperative changes in serum vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) concentrations and MBL2 genotypes interact in the development of restenosis.

METHODS

Eighty-two patients who underwent carotid eversion endarterectomy and were followed up by carotid duplex scan sonography for 14 months were studied. Growth factors were measured preoperatively and 4 days after surgery.

RESULTS

Pronounced significant increases in both VEGF and PDGF predicted restenosis but only in patients who were homozygous for the normal MBL2 genotype. In this group, the adjusted odds ratios of restenosis at 14 months in patients with high versus low early VEGF and PDGF increases were 27.73 (2.42 to 317.26) and 9.23 (1.45 to 58.70), respectively.

CONCLUSIONS

These findings indicate that the development of restenosis depends on both complement activation regulated by the MBL2 gene and pathologic processes leading to enhanced production of VEGF and PDGF during the very early postoperative period.

Interferon-gamma (IFN-γ) is a key cytokine in defense against mycobacteria, including Bacillus Calmette-Guérin (BCG). Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are pattern-recognizing molecules of innate immunity. The aim of the present study was to investigate the relationship between polymorphisms in MBL, TLR1, TLR2 and TLR6 encoding genes and stimulated IFN-γ and interleukin-12 (IL-12) ex vivo production in BCG osteitis survivors.

Data on single nucleotide polymorphisms in the MBL2 gene and TLR1, TLR2 and TLR6 genes were available from 132 former BCG osteitis patients, and data on ex vivo IFN-γ and IL-12 production were available from 115 and 118 patients, respectively. The present study is a secondary analysis of these available data. In an earlier study, we were able to characterize low IFN-γ and low IL-12 producers after BCG+IL-12 or BCG+IFN-γ stimulations, respectively.

Three patients had the homozygous variant MBL2 genotype, and one of them was a low IFN-γ producer (both concentration and response <5th percentile). The heterozygous variant MBL2 genotype showed no association with IFN-γ or IL-12 production. The TLR2 variant genotype was present in 14 subjects; 28.6% of them were low IFN-γ producers versus 7.8% of those 103 with the TLR2 wild genotype (P = 0.037). TLR1 or TLR6 polymorphisms had no significant associations with stimulated ex vivo IFN-γ or IL-12 production.

Preliminary evidence was found that variant genotypes of the MBL2 gene (if homozygous) and variant genotypes of the TLR2 gene (only heterozygotes present) are associated with low IFN-γ production.

The mannose-binding lectin MBL2 plays an important role in the innate immune system. It binds carbohydrates surface, acts as an opsonin and activates the complement system. With the aim of studying the evolution of the MBL2 gene in primates, we sequenced its coding region in 12 non-human primate species and compared them with the human sequence. We demonstrated that nucleotide and amino-acidic sequences of the MBL2 among primates are highly homologous, underlining the importance of this molecule in the defense system against pathogen invasions. In particular, in the collagen-like domain that confers the characteristic structure to MBL2 protein, the identity among primates is really high. In the carbohydrate recognition domain, we evidenced some primates' group-specific amino-acidic mutations not resulting in changes of the structure or function of this MBL2 domain. Phylogenetic analysis did not evidence any positive selective pressure in MBL2 gene among non-human primates. Our findings indicate that MBL2 is well conserved in agreement with its important role in the immune system: in non-human primates, we did not observe the same 'plasticity' of the MBL2 human gene, where a frequency of more than 1% of nucleotide variations was described in the coding and promoter regions.

Giardia is an intestinal protozoan parasite that has the ability to infect a wide range of hosts, which can result in the clinical condition 'giardiasis'. Over the years, experimental research has shown the crucial involvement of IL-17A to steer the protective immune response against Giardia. The development of the protective response, as reflected by a significant drop in cyst secretion, typically takes around 3 to 4 weeks. However, early-life infections often have a more chronic character lasting for several weeks or months. Therefore, the aim of the current study was to investigate the dynamics of a Giardia muris infection and the subsequent host immune response in neonatal mice infected 4 days after birth. The outcome of the study showed that a G. muris infection in pre-weaned mice failed to trigger a protective IL-17A response, which could explain the prolonged course of infection in comparison to older mice. Only after weaning, a protective intestinal immune response started to develop, characterized by an upregulation of IL-17A and Mbl2 and the secretion of parasite-specific IgA.

Building on studies showing that ischemia-reperfusion-(I/R)-injury is complement dependent, we tested links among complement activation, transplantation-associated I/R injury, and murine cardiac allograft rejection. We transplanted BALB/c hearts subjected to 8-h cold ischemic storage (CIS) into cytotoxic T-lymphocyte associated protein 4 (CTLA4)Ig-treated wild-type (WT) or c3-/- B6 recipients. Whereas allografts subjected to 8-h CIS rejected in WT recipients with a median survival time (MST) of 37 days, identically treated hearts survived >60 days in c3-/- mice (p < 0.05, n = 4-6/group). Mechanistic studies showed recipient C3 deficiency prevented induction of intragraft and serum chemokines/cytokines and blunted the priming, expansion, and graft infiltration of interferon-γ-producing, donor-reactive T cells. MST of hearts subjected to 8-h CIS was >60 days in mannose binding lectin (mbl1-/- mbl2-/- ) recipients and 42 days in factor B (cfb-/- ) recipients (n = 4-6/group, p < 0.05, mbl1-/- mbl2-/- vs. cfb-/- ), implicating the MBL (not alternative) pathway. To pharmacologically target MBL-initiated complement activation, we transplanted BALB/c hearts subjected to 8-h CIS into CTLA4Ig-treated WT B6 recipients with or without C1 inhibitor (C1-INH). Remarkably, peritransplantation administration of C1-INH prolonged graft survival (MST >60 days, p < 0.05 vs. controls, n = 6) and prevented CI-induced increases in donor-reactive, IFNγ-producing spleen cells (p < 0.05). These new findings link donor I/R injury to T cell-mediated rejection through MBL-initiated, complement activation and support testing C1-INH administration to prevent CTLA4Ig-resistant rejection of deceased donor allografts in human transplant patients.

The lectin pathway (LP) of complement activation is believed to contribute to brain inflammation. The study aims to identify the key components of the LP contributing to TBI outcome as possible novel pharmacological targets. We compared the long-term neurological deficits and neuropathology of wild-type mice (WT) to that of mice carrying gene deletions of key LP components after experimental TBI. WT or MASP-2 (Masp2^-/-), ficolin-A (Fcna^-/-), CL-11 (Colec11^-/-), MASP-1/3 (Masp1^-/-), MBL-C (Mbl2^-/-), MBL-A (Mbl1^-/-) or MBL^-/- (Mbl1^-/-/Mbl2^-/-) deficient male C57BL/6J mice were used. Mice underwent sham surgery or TBI by controlled cortical impact. The sensorimotor response was evaluated by neuroscore and beam walk tests weekly for 4 weeks. To obtain a comparative analysis of the functional outcome each transgenic line was rated according to a health score calculated on sensorimotor performance. For selected genotypes, brains were harvested 6 weeks after injury for histopathological analysis. MASP-2^-/-, MBL^-/- and FCN-A^-/- mice had better outcome scores compared to WT. Of these, MASP-2^-/- mice had the best recovery after TBI, showing reduced sensorimotor deficits (by 33% at 3 weeks and by 36% at 4 weeks). They also showed higher neuronal density in the lesioned cortex with a 31.5% increase compared to WT. Measurement of LP functional activity in plasma from MASP-2^-/- mice revealed the absence of LP functional activity using a C4b deposition assay. The LP critically contributes to the post-traumatic inflammatory pathology following TBI with the highest degree of protection achieved through the absence of the LP key enzyme MASP-2, underlining a therapeutic utility of MASP-2 targeting in TBI.

Keywords: Complement cascade; Lectin pathway; MBL-associated serine protease; Neuroinflammation; Neurological deficits; Pharmacological target; Traumatic brain injury.

Mannose-binding lectin (MBL) is a pattern recognition receptor of the lectin pathway of complement system. MBL binds to carbohydrates on microorganism's surfaces leading to complement activation, opsonization and phagocytosis. Polymorphisms in the MBL gene (MBL2) are associated with variations on MBL serum levels and with the susceptibility to various infectious and autoimmune diseases. The involvement of the lectin pathway in rheumatoid arthritis (RA) has been demonstrated by several studies and although MBL has been considered to have a dual role in the pathogenesis of the disease, the association between MBL and RA remains inconclusive. In an attempt to clarify this relationship, we developed this short review summarizing accumulated evidences in regard to MBL and RA and a meta-analysis to evaluate the influence of MBL2 polymorphisms on the susceptibility to RA. Among a total of 217 articles that were identified following a predefined search strategy on PubMed, Scopus, Scielo, EMBASE and Cochrane databases, only 13 met all inclusion criteria and were included in the meta-analysis. Data assessment was conducted by three independent investigators and presented in odds ratio (OR) and 95% confidence intervals (CIs) using forest plot charts. Both heterogeneity and publication bias were analyzed. The results of the meta-analysis evidenced that MBL2 low producing OO and XX genotypes do not confer higher risk to RA, even when data were analyzed according to cohort's ethnicity. Further studies are needed in order to clarify the importance of other genes of the lectin pathway in the pathogenesis of RA.

Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded (FFPE) samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. Genotyping of target polymorphisms in the MBL2 gene was performed by real-time PCR. Proinflammatory cytokines such as IL-6 and TNF-alpha presented higher tissue expression in the COVID-19 group compared to H1N1 and control groups. The same results were observed for ICAM-1 tissue expression. Increased expression of the FCN3 was observed in the COVID-19 group and H1N1 group compared to the control group. The MBL tissue expression was higher in the COVID-19 group compared to H1N1 and control groups. The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.

OBJECTIVE

The human mannose-binding lectin (MBL) and ficolins (FCN) are involved in pathogen recognition in the first line of defence. They support activation of the complement lectin cascade in the presence of MBL-associated serine protease 2 (MASP-2), a protein that cleaves the C4 and C2 complement components. Recent studies found that distinct MBL2 and FCN2 promoter variants and their corresponding serum levels are associated with relative protection from urogenital schistosomiasis.

METHODS

We investigated the contribution of MASP-2 levels and MASP2 polymorphisms in a Nigerian study group, of 163 individuals infected with Schistosoma haematobium and 183 healthy subjects.

RESULTS

MASP-2 serum levels varied between younger children (≤12 years) and older children (>12 years) and adults (P = 0.0001). Younger children with a patent infection had significantly lower MASP-2 serum levels than uninfected children (P = 0.0074). Older children and adults (>12 years) with a current infection had higher serum MASP-2 levels than controls (P = 0.032). MBL serum levels correlated positively with MASP-2 serum levels (P = 0.01). MASP2 secretor haplotypes were associated with MASP-2 serum levels in healthy subjects. The heterozygous MASP2 p.P126L variant was associated with reduced serum MASP-2 levels (P = 0.01).

CONCLUSIONS

The findings indicate that higher MASP-2 serum levels are associated with relative protection from urogenital schistosomiasis in Nigerian children.

UNASSIGNED

Evidence suggests that genetic variations of exon 1 of mannose-binding lectin 2 (MBL2) may contribute to tuberculosis (TB) risk. Many studies have investigated the association between MBL2 exon 1 polymorphisms (rs1800450, rs1800451, and rs5030737) and TB risk, but yielded inconclusive results.

UNASSIGNED

We conducted this meta-analysis of 26 eligible case-control studies that included 7952 cases and 9328 controls to identify the strength of association. Odds ratio (OR) and 95% CI were used to evaluate the strength of association. Statistical analyses were performed by using STATA 12.1.

UNASSIGNED

We found a statistically significant correlation between MBL2 exon 1 polymorphisms and increased TB risk among three models: allele model (O vs A: OR =1.18, 95% CI: 1.01-1.38, Pheterogeneity<0.0001, I2=85.8%), homozygote comparison (OO vs AA: OR =1.49, 95%CI: 1.02-2.18, Pheterogeneity<0.0001, I2=79.1%), dominant model (AO/OO vs AA: OR =1.20, 95% CI: 1.01-1.43, Pheterogeneity<0.0001, I2=83.5%), especially in studies based on Asian populations among five models: allele model (O vs A: OR =1.29, 95% CI: 1.11-1.51, Pheterogeneity<0.0001, I2=66.0%), homozygote comparison (OO vs AA: OR =1.67, 95% CI: 1.09-2.55, Pheterogeneity=0.008, I2=54.2%), heterozygote comparison (AO vs AA: OR =1.26, 95% CI: 1.05-1.50, Pheterogeneity=0.001, I2=62.9%), dominant model (AO/OO vs. AA: OR =1.31, 95% CI: 1.10-1.56, Pheterogeneity=0.001, I2=64.2%), and recessive model (OO vs AO/AA: OR =1.50, 95% CI: 1.01-2.22, Pheterogeneity=0.023, I2=48.0%). Meta-regression results revealed that source of controls (p=0.009), but not ethnicity (p=0.687), genotyping method (p=0.231), and sample size (p=0.451) contributed to the source of heterogeneity.

UNASSIGNED

This meta-analysis suggests that MBL2 exon 1 polymorphisms may contribute to TB risk, especially in Asian populations.

We conducted a prospective study of 453 Polish patients suffering from pulmonary tuberculosis and 267 healthy controls. Selected polymorphisms of the genes encoding for collectins, ficolins and MBL-associated serine protease 2 were investigated as were serum concentrations of mannose-binding lectin, surfactant protein D, ficolin-1 and ficolin-3. The number of MBL2 gene exon 1 variant allele carriers was significantly higher in patients, compared with controls. The homozygosity for SFTPA2 +26 C > A SNP variant allele occurred less commonly within TB, while homozygosity for the FCN1 -542 G > A major allele was less frequent within the control group. Two patients were found MASP-2-deficient. Serum concentrations of MBL, SP-D and ficolin-1 were higher amongst patients while the converse was found for ficolin-3. Ficolin-1 had high specificity to differentiate between individuals with tuberculosis and healthy persons and therefore may be considered potential disease marker.

A 7.3-kDa antifungal peptide with an N-terminal sequence exhibiting remarkable homology to defensins from other leguminous plants was isolated from Phaseolus vulgaris cv. 'Spotted Bean'. The isolation procedure involved ion exchange chromatography on O-diethylaminoethyl (DEAE) cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The peptide was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel and SP-Sepharose. It exerted an antifungal action on Fusarium oxysporum and Mycosphaerella arachidicola. It inhibited mycelial growth in F. oxysporum with an IC(50) value of 1.8 microM. It suppressed [methyl-(3)H]-thymidine incorporation by leukemia L1210 cells and MBL2 cells with an IC(50) value of 4.0 and 9.0 microM, respectively. There was no effect on HIV-1 reverse transcriptase activity when the peptide was tested up to 0.1 mM.

UNASSIGNED

Patients with end-stage renal disease (ESRD) have high morbidity and mortality rates, with cardiovascular diseases and infections being the major causes of death. Mannose-binding lectin (MBL) has been suggested to play a protective role in this regard. The aim of this study was to investigate a possible clinical association of MBL genotypes (MBL2) with outcome among patients on dialysis or with a functioning graft.

UNASSIGNED

A total of 98 patients with ESRD accepted for living-donor renal transplantation or on the waiting list for transplantation were included and prospectively followed for an average of 9 years (range 7.5-9.9). Medical records were evaluated regarding transplantation status, diabetes mellitus, vascular parameters and infections for all the patients. Cox regression models and logistic regression analysis were used for statistical analyses. The cohort was divided into two groups according to the MBL2 genotype (normal A/A versus variant A/O or O/O).

UNASSIGNED

We found no evidence for an association between the MBL2 genotype and all-cause mortality, cardiovascular events or bacterial infections (pneumonia, urinary tract infection, fistula infection or other infections).

UNASSIGNED

In this cohort, the MBL2 genotype did not seem to be associated with any long-term clinical effects in ESRD patients on dialysis or with a functioning graft.

Since antiretroviral drugs have been introduced to prevent mother-to-child transmission, the risk of HIV-1 infection in infants has decreased considerably worldwide. Nevertheless, many factors are involved in viral transmission and host susceptibility to infection. The immune system and its components, including mannose binding protein C (encoding by MBL2 gene), are already known to play an important role in this scenario. In the present study, 313 children and 98 of their mothers from Zambia were genotyped for the MBL2 promoter HL (rs11003125) and XY (rs7096206) polymorphisms and exon 1 D (rs5030737, at codon 52) B (rs1800450, at codon 54) and C (rs1800451, at codon 57) polymorphisms in order to investigate the potential role of these genetic variants in HIV-1 mother-to-child transmission. No statistical significant association was observed comparing transmitter and non-transmitter mothers and also confronting HIV-positive and HIV-negative children. The findings of the current study obtained on mother and children from Zambia evidence lack of association between MBL2 functional polymorphisms and HIV-1 mother-to-child transmission.

Background: New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients.

Methods: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.

Results: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.

Conclusion: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.

Keywords: Cyclosporine; Immunosuppression; New-onset diabetes; Polymorphism; Post-renal transplant; Risk factors.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Genetic factors associated with immune response contribute to infection development and disease. M. leprae has the capacity to invade Schwann cells in the peripheral nervous system and cause neuropathy. However, while the responsible molecular mechanisms remain to be fully unveiled, they have begun being elucidated. We studied genetic variants Myelin Protein Zero (MPZ), a major structural component of the myelin sheath, and Mannose Binding Lectin 2 (MBL2), a protein involved in immune response, in 112 family groups of 114 leprosy patients using PCR-RFLP, aiming to calculate the association and allelic transmission of variants associated in first, second and third-degree relatives. Polymorphisms found in MPZ and MBL2 showed association with leprosy. Different probabilities for allelic transmission were found for first and second-degree relatives, a fact that is important to take into account when evaluating risk in contacts of leprosy patients. Structural analysis allows the study of putative amino acids and their possible effect on protein structure and function, as well as on the assembly of a protein homotetramer. Our results suggest that the identified MPZ and MBL2 gene mutations are associated with leprosy in a Colombian population, which correlates with MPZ and MBL2 protein function, and increase the risk of M. leprae infection in leprosy-patients' family members. Additionally, structural analyses were carried out specifically for MPZ protein using information available in databases, and analyzing the substitutions in wildtype and mutant protein. The results show significant structural changes, which may be associated to infection and pathogenicity.