Dataset Information

Association of MBL2 Exon 1 Polymorphisms With Multibacillary Leprosy.

ABSTRACT: Mannose-binding lectin (MBL) is a serum protein of innate immunity, with a central role in the activation of the complement system through the lectin pathway. This protein is encoded by MBL2 gene, and single-nucleotide polymorphisms located at exon 1, such as rs5030737 C>T (D variant), rs1800450 G>A (B variant), and rs1800451 G>A (C variant), may change the MBL structure and the serum concentration. MBL2 polymorphisms have been associated with several infectious diseases, including leprosy. Host immune response has a major impact on the clinical manifestation of leprosy since only a few individuals infected with Mycobacterium leprae will develop the disease. Therefore, the aim of this study was to evaluate the influence of MBL2 exon 1 polymorphisms (rs5030737, rs1800450, and rs1800451) on the MBL levels and leprosy immunopathogenesis. This case-control study included 350 leprosy patients from Southern Brazil, with 279 classified as multibacillary (MB) and 71 as paucibacillary (PB). The control group consisted of 350 non-consanguineous individuals, who were not diagnosed with leprosy or other infectious and autoimmune diseases. Genotyping was performed by PCR-sequence specific primers, and the MBL serum concentrations were evaluated by ELISA. MBL2 exon 1 polymorphisms were analyzed individually and grouped as genotypes, considering "A" as the wild allele and "O" as the presence of at least one polymorphism (D, B, or C variants). Differences were not observed in the distribution of genotypic and allelic frequencies between leprosy per se patients and controls. However, in a haplotypic analysis, the TGG haplotype presented a risk for development of leprosy per se in women when compared to the wild haplotype (CGG) (OR = 2.69). Comparing patients with MB and PB, in a multivariate analysis, the B variant was associated with the susceptibility of developing the MB form of leprosy (OR = 2.55). Besides that, the CAG haplotype showed an increased susceptibility to develop MB leprosy in women compared to men. It was observed that the A/O genotype in women was associated with a susceptibility to leprosy development per se (OR = 1.66) and progression to MB leprosy (OR = 3.13). In addition, the MBL serum concentrations were in accordance with the genotyping analysis. In summary, our data suggest that MBL2 exon 1 polymorphisms are associated with an increased risk to leprosy development and progression.

SUBMITTER: Tiyo BT

PROVIDER: S-EPMC7494844 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of MBL2 Exon 1 Polymorphisms With Multibacillary Leprosy.

Tiyo Bruna Tiaki BT Vendramini Evelyn Castillo Lima ECL de Souza Victor Hugo VH Colli Cristiane Maria CM Alves Hugo Vicentin HV Sell Ana Maria AM Zucoloto Sylmara Bessani Paixão SBP Visentainer Jeane Eliete Laguila JEL

Frontiers in immunology 20200903

Mannose-binding lectin (MBL) is a serum protein of innate immunity, with a central role in the activation of the complement system through the lectin pathway. This protein is encoded by MBL2 gene, and single-nucleotide polymorphisms located at exon 1, such as rs5030737 C>T (D variant), rs1800450 G>A (B variant), and rs1800451 G>A (C variant), may change the MBL structure and the serum concentration. MBL2 polymorphisms have been associated with several infectiou ...[more]

PMID: 33013845

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Project description:BackgroundThe gene MASP2 (mannan-binding lectin (MBL)-associated serine protease 2) encodes two proteins, MASP-2 and MAp19 (MBL-associated protein of 19 kDa), bound in plasma to MBL and ficolins. The binding of MBL/MASP-2 and ficolin/MASP-2 complexes to microorganisms activates the lectin pathway of complement and may increase the ingestion of intracellular pathogens such as Mycobacterium leprae.MethodsWe haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 219 Brazilian leprosy patients (131 lepromatous, 29 borderline, 21 tuberculoid, 14 undetermined, 24 unspecified), 405 healthy Brazilians and 291 Danish blood donors with previously determined MASP-2 and MAp19 levels. We also evaluated MASP-2 levels in further 46 leprosy patients and 69 Brazilian controls.ResultsTwo polymorphisms flanking exon 5 of MASP2 were associated with a dominant effect on high MASP-2 levels and an additive effect on low MAp19 levels. Patients presented lower MASP-2 levels (P?=?0.0012) than controls. The frequency of the p.126L variant, associated with low MASP-2 levels (below 200 ng/mL), was higher in the patients (P?=?0.0002, OR?=?4.92), as was the frequency of genotypes with p.126L (P?=?0.00006, OR?=?5.96). The *1C2-l [AG] haplotype, which harbors p.126L and the deficiency-causing p.439H variant, has a dominant effect on the susceptibility to the disease (P?=?0.007, OR?=?4.15). Genotypes composed of the *2B1-i and/or *2B2A-i haplotypes, both associated with intermediate MASP-2 levels (200-600 ng/mL), were found to be protective against the disease (P?=?0.0014, OR?=?0.6). Low MASP-2 levels (P?=?0.022), as well as corresponding genotypes with *1C2-l and/or *2A2-l but without *1B1-h or *1B2-h, were more frequent in the lepromatous than in other patients (P?=?0.008, OR?=?8.8).ConclusionsIn contrast with MBL, low MASP-2 levels increase the susceptibility to leprosy in general and to lepromatous leprosy in particular. MASP2 genotypes and MASP-2 levels might thus be of prognostic value for leprosy progression.

Project description:BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae, predominantly affecting the peripheral nerves, resulting in sensory and motor deficits in the feet. Foot ulcers and imbalances are frequent manifestations in leprosy, often correlating with diminished sensitivity. While clinical scales and monofilament esthesiometers are conventionally utilized to evaluate foot sensitivity and balance in these patients, their discriminatory power is limited and their effectiveness is greatly dependent on the examiner's proficiency. In contrast, baropodometry and posturography offer a more comprehensive evaluation, aiming to preempt potential damage events. This study aimed was to assess the correlation between baropodometry and force plate measurements in leprosy patients and control participants, to improve the prevention and treatment of foot ulcers and complications associated with leprosy.MethodologyThis cross-sectional study was conducted during 2022 and enrolled 39 participants (22 patients with multibacillary leprosy and 17 non-leprosy controls). Demographic data were collected, and a monofilament esthesiometer was used to assess sensory deficits. In addition, physical examinations and balance and plantar pressure tests were conducted. The Student's t-test was used to compare mean and maximum plantar pressures between groups. For most COP variables, a Mann-Whitney Wilcoxon test was used, except for AP amplitude which was analyzed with the Student's t-test due to its normal distribution. The relationship between foot pressure and balance control was assessed using Spearman's correlation, focusing on areas with significant pressure differences between groups.Principal findingsLeprosy patients showed increased pressure in forefoot areas (T1, M1, T2-T5, and M2) and decreased pressure in hindfoot regions (MH and LH) compared to controls. These patients also displayed higher AP and ML amplitudes, suggesting poorer COP control. Correlation analyses between the two groups revealed that foot plantar pressures significantly impact balance control. Specifically, increased T1 region pressures correlated with greater sway in balance tasks, while decreased MH region pressures were linked to reduced COP control.Conclusions/significanceThe findings suggest a joint disturbance of plantar pressure distribution and static balance control in leprosy patients. These alterations may increase the risk of tissue injuries, including calluses and deformities, as well as falls.

Project description:BackgroundThe ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions.Methodology/principal findingsThree hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads.Conclusions/significanceLeprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.

Dataset Information

Association of MBL2 Exon 1 Polymorphisms With Multibacillary Leprosy.

Publications

Association of <i>MBL2</i> Exon 1 Polymorphisms With Multibacillary Leprosy.

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