Gait analysis of leprosy patients with foot drop using principal component analysis.

BACKGROUND: Peripheral nerve injury caused by leprosy can lead to foot drop, resulting in an altered gait pattern that has not been previously described using 3D gait analysis. METHODS: Gait kinematics and dynamics were analyzed in 12 patients with unilateral foot drop caused by leprosy and in 15 healthy controls. Biomechanical data from patients' affected and unaffected limbs were compared with controls using inferential statistics and a standard distance, based on principal components analysis (PCA). FINDINGS: Patients walked slower than controls (0.8 ± 0.2 vs. 1.1 ± 0.2 m/s, p = 0.003), with a reduced stance and increased swing percentage. The affected limb increased (p < 0.05) plantar flexion at the initial contact (-16.8o ± 8.3), terminal stance (-29.1o ± 11.5), and swing (-12.4o ± 6.2) in the affected limb compared to unaffected (-6.6o ± 10.3; -14.6o ± 11.6; 2.4o ± 7.6) and controls (-5.4o ± 2.5; -18.8o ± 5.8; -1.4o ± 3.9). Increased pelvic tilt and knee adduction/abduction range, with lower hip adduction, were observed. The second peak of ground reaction force (98.6 ± 5.2 %BW), ankle torque (0.99 ± 0.33 Nm/kg), and net ankle work in stance (-0.03 ± 5.4 J/Kg) decreased in the affected limb compared to controls (104.1 ± 5.5 %BW; 1.24 ± 0.4 Nm/kg; -4.58 ± 5.19 J/kg; p < 0.05). There were decreasing multivariate standard distances in the affected limb compared with the unaffected and controls. PCA loading factors highlighted the major differences between groups. INTERPRETATION: Leprosy patients with foot drop presented altered gait patterns in affected and unaffected limbs. There were remarkable differences in ankle kinematics and dynamics. Rehabilitation devices, such as ankle foot orthosis or tendon transfer surgeries to increase ankle dorsiflexion, could benefit these patients and reduce deviations from normal gait.

Investigating Bacterial Volatilome for the Classification and Identification of Mycobacterial Species by HS-SPME-GC-MS and Machine Learning.

Species of Mycobacteriaceae cause disease in animals and humans, including tuberculosis and leprosy. Individuals infected with organisms in the Mycobacterium tuberculosis complex (MTBC) or non-tuberculous mycobacteria (NTM) may present identical symptoms, however the treatment for each can be different. Although the NTM infection is considered less vital due to the chronicity of the disease and the infrequency of occurrence in healthy populations, diagnosis and differentiation among Mycobacterium species currently require culture isolation, which can take several weeks. The use of volatile organic compounds (VOCs) is a promising approach for species identification and in recent years has shown promise for use in the rapid analysis of both in vitro cultures as well as ex vivo diagnosis using breath or sputum. The aim of this contribution is to analyze VOCs in the culture headspace of seven different species of mycobacteria and to define the volatilome profiles that are discriminant for each species. For the pre-concentration of VOCs, solid-phase micro-extraction (SPME) was employed and samples were subsequently analyzed using gas chromatography-quadrupole mass spectrometry (GC-qMS). A machine learning approach was applied for the selection of the 13 discriminatory features, which might represent clinically translatable bacterial biomarkers.

Influence of Debaryomyces hansenii on bacterial lactase gene diversity in intestinal mucosa of mice with antibiotic-associated diarrhea.

AIM: The current study aimed to investigate the effects of Debaryomyces hansenii on the diversity of bacterial lactase gene in the intestinal mucosa of antibiotic-associated diarrhea (AAD) mice. METHODS: Eighteen mice were randomly divided into three groups (6 mice per group): healthy control group, diarrhea model group and D. hansenii treatment group. The antibiotic-associated diarrhea model was established by intragastric administration with a mixture of cephradine and gentamicin sulfate (23.33 mL·kg-1·d-1) twice a day for 5 days continuously. After establishing the AAD model, the mice in the D. hansenii treatment group were gavaged with D. hansenii for three days, while other groups were gavaged with distilled water. Then, the intestinal mucosa of all three groups was collected and DNA was extracted in an aseptic environment for the following analysis. RESULTS: The difference in the richness and homogeneity of the bacterial lactase gene among all samples were inapparent, as the difference in the Chao1, ACE, Simpson and Shannon indices among the three groups were insignificant (P>0.05). NMDS analysis also showed that the distance of the samples among the three groups was unobvious. Furthermore, the bacterial lactase gene in the mucosa mainly originated from Actinobacteria, Firmicutes and Proteobacteria. Compared with the healthy control group, the abundance of lactase genes originating from Cupriavidus, Lysobacter, Citrobacter, Enterobacter and Pseudomonas was increased in the D. hansenii treatment group, while the lactase gene from Acidovorax and Stenotrophomonas decreased (p < 0.01 or p < 0.05) in the diarrhea model group and the D. hansenii treatment group. CONCLUSION: D. hansenii was capable of improving the growth of some key lactase-producing bacteria like Deinococcus, Cupriavidus and Lysobacter for treating AAD.

Type of starter culture influences on structural and sensorial properties of low protein fermented gels.

Organoleptic properties of skimmed milk fermented gels are progressively demanding to produce optimal quality yogurts. Chr-Hansen trademark registered cultures were used to produce low-protein (3.4%) gels to assess the ability to redesign the sensorial and textural properties with the choice of starter culture. Resulting gels were assessed for sensorial, textural, rheological, and microstructural properties and compared with a commercial control (4.5% protein). Mouth thickness, syneresis, firmness, elasticity, and consistency values were lower for polysaccharides-producing cultures. Such cultures contributed to the higher creaminess and tended to give higher ropiness. Observed differences among microstructures of the gel were minute. Microstructural and rheological data corresponded and reflected the instrumental and sensory interpretations. Strong correlations were observed between sensory and instrumental data. Nonprobiotics cultures resulted in promising overall gel properties compared with probiotic cultures according to the principal component analysis. Yet probiotic cultures resulted in lower syneresis than nonprobiotic cultures. Thus, the choice of bacterial culture modifies the sensorial and textural properties of fermented gel with strong correlations, as a result of altered gel network formation with the production of polysaccharides. Inferior textural and sensorial quality aspects, particularly at low protein levels, have negative impact on consumer demand of low protein yogurts. Thus, we attempted to gain required gel textural and sensorial properties with a choice of starter culture with a low protein level. Resulting gel properties at lowered protein content with different starter cultures are not fully known. The present study compares the effect of probiotic and nonprobiotic starter cultures on gel properties, as gel texture and sensory properties are of great interest and thus not willing to be compromised. In addition, we examined the overall texture profile of studied cultures and correlate with sensory properties. Therefore, reducing protein level in milk and achieving required gel properties with the choice of appropriate starter culture is of great commercial interest as a cost-cutting strategy to produce low-cost optimum quality yogurt.

[Instrument to evaluate the combination of foods to make iron more bioavailable in the diet]. / Instrumento para avaliar a combinação de alimentos para tornar o ferro mais biodisponível na dieta.

The scope of this research was to develop an instrument to evaluate the knowledge which adult women have of food combinations in order to make iron bioavailable in the diet of children. An exploratory factor analysis study (Likert scale) was conducted applying a questionnaire on a sample comprising 151 women and then applying Principal Factor Analysis and Likelihood Ratio Analysis. The Kaiser-Meyer-Olkin (KMO) test, the Doornik-Hansen test, the Kaiser Guttman criterion and the correlation between factors and theoretical assumptions were applied. Reliability was assessed by Cronbach's alpha and composite reliability. Total KMO (0.5942) showed the adequacy of the sample. The Doornik-Hansen test showed multivariate normality of the scores observed. Factorial loads, error variance of items and correlation between factors pointed to the two-dimensional nature of the questionnaire, which decreased from 30 to 15 items. Total Cronbach's alpha was 0.8018 (95% CI = 0.7429 to 0.8606) and composite reliability (Factor 1 = 0.3125 and Factor 2 = 0.3263). Convergent and discriminant factorial validity revealed acceptable results. A decision was taken to reduce the instrument (from 30 to 15 items) with sufficient reliability and validity that enable it to qualify for further confirmatory factor analysis procedures.

O objetivo foi desenvolver um instrumento para avaliar o conhecimento de mulheres adultas sobre a combinação de alimentos de forma a tornar o ferro biodisponível na dieta infantil. Estudo fatorial exploratório de questionário (escala Likert) utilizando-se Análise de Fator Principal e estimador de razão de verossimilhança. Aplicaram-se teste KMO, teste Doornik-Hansen, critério de Kaiser Guttman, correlação entre fatores e pressupostos teóricos. Confiabilidade avaliada pelo Alfa de Cronbach e confiabilidade composta. Participaram do estudo 151 mulheres. KMO total (0,5942) mostrou adequação da amostra. Teste Doornik-Hansen atestou normalidade multivariada dos escores observados. Cargas fatoriais, variância do erro dos itens e correlação entre os fatores apontaram para a bidimensionalidade do questionário, que passou de 30 para 15 itens. Alfa de Cronbach total de 0,8018 (95% IC = 0,7429 a 0,8606) e confiabilidade composta (Fator 1 = 0,3125 e Fator 2 = 0,3263). Validade fatorial convergente e discriminante apresentaram resultados aceitáveis. Concluiu-se por redução de instrumento validado (30 para 15 itens) com confiabilidade e validade que o habilita para posterior procedimento de análise fatorial confirmatória.

Instrumento para avaliar a combinação de alimentos para tornar o ferro mais biodisponível na dieta / Instrument to evaluate the combination of foods to make iron more bioavailable in the diet

Resumo O objetivo foi desenvolver um instrumento para avaliar o conhecimento de mulheres adultas sobre a combinação de alimentos de forma a tornar o ferro biodisponível na dieta infantil. Estudo fatorial exploratório de questionário (escala Likert) utilizando-se Análise de Fator Principal e estimador de razão de verossimilhança. Aplicaram-se teste KMO, teste Doornik-Hansen, critério de Kaiser Guttman, correlação entre fatores e pressupostos teóricos. Confiabilidade avaliada pelo Alfa de Cronbach e confiabilidade composta. Participaram do estudo 151 mulheres. KMO total (0,5942) mostrou adequação da amostra. Teste Doornik-Hansen atestou normalidade multivariada dos escores observados. Cargas fatoriais, variância do erro dos itens e correlação entre os fatores apontaram para a bidimensionalidade do questionário, que passou de 30 para 15 itens. Alfa de Cronbach total de 0,8018 (95% IC = 0,7429 a 0,8606) e confiabilidade composta (Fator 1 = 0,3125 e Fator 2 = 0,3263). Validade fatorial convergente e discriminante apresentaram resultados aceitáveis. Concluiu-se por redução de instrumento validado (30 para 15 itens) com confiabilidade e validade que o habilita para posterior procedimento de análise fatorial confirmatória.

Abstract The scope of this research was to develop an instrument to evaluate the knowledge which adult women have of food combinations in order to make iron bioavailable in the diet of children. An exploratory factor analysis study (Likert scale) was conducted applying a questionnaire on a sample comprising 151 women and then applying Principal Factor Analysis and Likelihood Ratio Analysis. The Kaiser-Meyer-Olkin (KMO) test, the Doornik-Hansen test, the Kaiser Guttman criterion and the correlation between factors and theoretical assumptions were applied. Reliability was assessed by Cronbach's alpha and composite reliability. Total KMO (0.5942) showed the adequacy of the sample. The Doornik-Hansen test showed multivariate normality of the scores observed. Factorial loads, error variance of items and correlation between factors pointed to the two-dimensional nature of the questionnaire, which decreased from 30 to 15 items. Total Cronbach's alpha was 0.8018 (95% CI = 0.7429 to 0.8606) and composite reliability (Factor 1 = 0.3125 and Factor 2 = 0.3263). Convergent and discriminant factorial validity revealed acceptable results. A decision was taken to reduce the instrument (from 30 to 15 items) with sufficient reliability and validity that enable it to qualify for further confirmatory factor analysis procedures.

Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation.

Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong host genetic contribution to leprosy susceptibility is well established. However, the modulation of the transcriptional response to infection and the mechanism(s) of disease control are poorly understood. To address this gap in knowledge of leprosy pathogenicity, we conducted a genome-wide search for expression quantitative trait loci (eQTL) that are associated with transcript variation before and after stimulation with M. leprae sonicate in whole blood cells. We show that M. leprae antigen stimulation mainly triggered the upregulation of immune related genes and that a substantial proportion of the differential gene expression is genetically controlled. Indeed, using stringent criteria, we identified 318 genes displaying cis-eQTL at an FDR of 0.01, including 66 genes displaying response-eQTL (reQTL), i.e. cis-eQTL that showed significant evidence for interaction with the M. leprae stimulus. Such reQTL correspond to regulatory variations that affect the interaction between human whole blood cells and M. leprae sonicate and, thus, likely between the human host and M. leprae bacilli. We found that reQTL were significantly enriched among binding sites of transcription factors that are activated in response to infection, and that they were enriched among single nucleotide polymorphisms (SNPs) associated with susceptibility to leprosy per se and Type-I Reaction, and seven of them have been targeted by recent positive selection. Our study suggested that natural selection shaped our genomic diversity to face pathogen exposure including M. leprae infection.

Σpider diagram: a universal and versatile approach for system comparison and classification: application to solvent properties.

Classification methods based on physico-chemical properties are very useful in analytical chemistry, both for extraction and separation processes. Depending on the number of parameters, several classification approaches can be used: by plotting two- or three-dimensional maps (triangles, cubes, spheres); by calculating comparison values for one system with reference to another one, i.e. the ranking factor F, or the Neue selectivity difference s(2); or with chemometric methods (principal component analysis-PCA or hierarchical cluster analysis-HCA). All these methods display advantages and drawbacks: some of them are limited by the number of studied parameters (e.g. three for triangle or sphere plots); others require a new calculation when changing the reference point (F; s(2)), while for chemometric methods (PCA, HCA), the relationships between the clusters and the physico-chemical properties are not always easily understandable. From previous studies performed in supercritical fluid chromatography for stationary phase classification on the basis of linear solvation energy relationships (LSER) including five parameters, we developed a classification map called the Σpider diagram. This diagram allows plotting in a two-dimensional map the location of varied systems, having as many parameters as the ones required getting a satisfactory classification. It can be three, five, eight, or any number. In the present paper, we apply this diagram, and the calculation mode to obtain this diagram, to different solvent classifications: Snyder triangle, solvatochromic solvent selectivity, Hansen parameters, and also to LSER Abraham descriptors and COSMO-RS parameters. The new figure based on Snyder data does not change the global view of groups, except by the use of corrected data from literature, and allows adding the polarity value onto the map. For the solvatochromic solvent selectivity, it leads to achieve a better view of solvents having no acidic character. For Hansen parameters, the "flattening" of the spherical view down to a single plane could be found easier to use. For COSMO-RS and with Abraham descriptor, a more subtle classification is achieved, mainly due to the use of five parameters instead of three. A strong reversed correlation is established between the Rohrschneider polarity P' and the normalized V (molecular volume) parameter. The study of the location of solvents used for reversed-phase liquid chromatography and the Arizona system for counter-current chromatography is discussed, as well as the replacement of unsafe solvents by greener ones, or the use of these classifications for the study of compound solubility. Besides, this paper also shows the ability to the spider diagram to plot on a single plane three axes from principal component analyses.

Genetic evidence of African slavery at the beginning of the trans-Atlantic slave trade.

An archaeological excavation in Valle da Gafaria (Lagos, Portugal), revealed two contiguous burial places outside the medieval city walls, dating from the 15(th)-17(th) centuries AD: one was interpreted as a Leprosarium cemetery and the second as an urban discard deposit, where signs of violent, unceremonious burials suggested that these remains may belong to slaves captured in Africa by the Portuguese. We obtained random short autosomal sequence reads from seven individuals: two from the latter site and five from the Leprosarium and used these to call SNP identities and estimate ancestral affinities with modern reference data. The Leprosarium site samples were less preserved but gave some probability of both African and European ancestry. The two discard deposit burials each gave African affinity signals, which were further refined toward modern West African or Bantu genotyped samples. These data from distressed burials illustrate an African contribution to a low status stratum of Lagos society at a time when this port became a hub of the European trade in African slaves which formed a precursor to the transatlantic transfer of millions.

Utilization of coffee by-products obtained from semi-washed process for production of value-added compounds.

The semi-dry processing of coffee generates significant amounts of coffee pulp and wastewater. This study evaluated the production of bioethanol and volatile compounds of eight yeast strains cultivated in a mixture of these residues. Hanseniaspora uvarum UFLA CAF76 showed the best fermentation performance; hence it was selected to evaluate different culture medium compositions and inoculum size. The best results were obtained with 12% w/v of coffee pulp, 1 g/L of yeast extract and 0.3 g/L of inoculum. Using these conditions, fermentation in 1 L of medium was carried out, achieving higher ethanol yield, productivity and efficiency with values of 0.48 g/g, 0.55 g/L h and 94.11% respectively. Twenty-one volatile compounds corresponding to higher alcohols, acetates, terpenes, aldehydes and volatile acids were identified by GC-FID. Such results indicate that coffee residues show an excellent potential as substrates for production of value-added compounds. H. uvarum demonstrated high fermentative capacity using these residues.

NOD2 triggers an interleukin-32-dependent human dendritic cell program in leprosy.

It is unclear whether the ability of the innate immune system to recognize distinct ligands from a single microbial pathogen via multiple pattern recognition receptors (PRRs) triggers common pathways or differentially triggers specific host responses. In the human mycobacterial infection leprosy, we found that activation of monocytes via nucleotide-binding oligomerization domain-containing protein 2 (NOD2) by its ligand muramyl dipeptide, as compared to activation via heterodimeric Toll-like receptor 2 and Toll-like receptor 1 (TLR2/1) by triacylated lipopeptide, preferentially induced differentiation into dendritic cells (DCs), which was dependent on a previously unknown interleukin-32 (IL-32)-dependent mechanism. Notably, IL-32 was sufficient to induce monocytes to rapidly differentiate into DCs, which were more efficient than granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived DCs in presenting antigen to major histocompatibility complex (MHC) class I-restricted CD8(+) T cells. Expression of NOD2 and IL-32 and the frequency of CD1b(+) DCs at the site of leprosy infection correlated with the clinical presentation; they were greater in patients with limited as compared to progressive disease. The addition of recombinant IL-32 restored NOD2-induced DC differentiation in patients with the progressive form of leprosy. In conclusion, the NOD2 ligand-induced, IL-32-dependent DC differentiation pathway contributes a key and specific mechanism for host defense against microbial infection in humans.

Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy.

We performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance: rs2275606 (combined P = 3.94 × 10(-14), OR = 1.30) on 6q24.3 and rs3762318 (combined P = 3.27 × 10(-11), OR = 0.69) on 1p31.3. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy. Furthermore, we identified evidence of interaction between the NOD2 and RIPK2 loci, which is consistent with the biological association of the proteins encoded by these genes (NOD2-RIPK2 complex) in activating the NF-κB pathway as a part of the host defense response to infection. Our findings have expanded the biological functions of IL23R by uncovering its involvement in infectious disease susceptibility and suggest a potential involvement of autophagocytosis in leprosy pathogenesis. The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.

Identification, replication, and functional fine-mapping of expression quantitative trait loci in primary human liver tissue.

The discovery of expression quantitative trait loci ("eQTLs") can help to unravel genetic contributions to complex traits. We identified genetic determinants of human liver gene expression variation using two independent collections of primary tissue profiled with Agilent (n = 206) and Illumina (n = 60) expression arrays and Illumina SNP genotyping (550K), and we also incorporated data from a published study (n = 266). We found that ∼30% of SNP-expression correlations in one study failed to replicate in either of the others, even at thresholds yielding high reproducibility in simulations, and we quantified numerous factors affecting reproducibility. Our data suggest that drug exposure, clinical descriptors, and unknown factors associated with tissue ascertainment and analysis have substantial effects on gene expression and that controlling for hidden confounding variables significantly increases replication rate. Furthermore, we found that reproducible eQTL SNPs were heavily enriched near gene starts and ends, and subsequently resequenced the promoters and 3'UTRs for 14 genes and tested the identified haplotypes using luciferase assays. For three genes, significant haplotype-specific in vitro functional differences correlated directly with expression levels, suggesting that many bona fide eQTLs result from functional variants that can be mechanistically isolated in a high-throughput fashion. Finally, given our study design, we were able to discover and validate hundreds of liver eQTLs. Many of these relate directly to complex traits for which liver-specific analyses are likely to be relevant, and we identified dozens of potential connections with disease-associated loci. These included previously characterized eQTL contributors to diabetes, drug response, and lipid levels, and they suggest novel candidates such as a role for NOD2 expression in leprosy risk and C2orf43 in prostate cancer. In general, the work presented here will be valuable for future efforts to precisely identify and functionally characterize genetic contributions to a variety of complex traits.

Functional connectivity metrics during stroke recovery.

We explore functional connectivity in nine subjects measured with 1.5T fMRI-BOLD in a longitudinal study of recovery from unilateral stroke affecting the motor area (Small et al., 2002). We found that several measures of complexity of covariance matrices show strong correlations with behavioral measures of recovery. In Schmah et al. (2010), we applied Linear and Quadratic Discriminants (LD and QD) computed on a principal components (PC) subspace to classify the fMRI volumes into "early" and "late" sessions. We demonstrated excellent classification accuracy with QD but not LD, indicating that potentially important differences in functional connectivity exist between the early and late sessions. Motivated by Mclntosh et al. (2008), who showed that EEG brain-signal variability and behavioral performance both increased with age during development, we investigated complexity of the covariance matrix for this longitudinal stroke recovery data set. We used three complexity measures: the sphericity index described by Abdi (2010); "unsupervised dimensionality", which is the number of PCs that minimizes unsupervised generalization error of a covariance matrix (Hansen et al., 1999); and "QD dimensionality", which is the number of PCs that minimizes the classification accuracy of QD. Although these approaches measure different kinds of complexity, all showed strong correlations with one or more behavioral tests: nine-hole peg test, hand grip test and pinch test. We could not demonstrate that either sphericity or unsupervised dimensionality were significantly different for the "early" and "late" sessions using a paired Wilcoxon test. However, the amount of relative behavioral improvement was correlated with sphericity of the overall covariance matrix (pooled across all sessions), as well as with the divergence of the eigenspectra between the "early" and "late" covariance matrices. Complexity measures that use the number of PCs (which optimize QD classification or unsupervised generalization) were correlated with the behavioral performance of the final session, but not with the relative improvement. These are suggestive, but limited, results given the sample size, restricted behavioral measurements and older 1.5T BOLD data sets. Nevertheless, they indicate one potentially fruitful direction for future data-driven fMRI studies of stroke recovery in larger, better-characterized longitudinal stroke data sets recorded at higher field strength. Finally, we produced sensitivity maps (Kjems et al., 2002) corresponding to both linear and quadratic discriminants for the "early" vs. "late" classification. These maps measure the influence of each voxel on the class assignments for a given classifier. Differences between the scaled sensitivity maps for the linear and quadratic discriminants indicate brain regions involved in changes in functional connectivity. These regions are highly variable across subjects, but include the cerebellum and the motor area contralateral to the lesion.

Selection of solubility parameters for characterization of pharmaceutical excipients.

The solubility parameter (delta(2)), corrected solubility parameter (delta(T)) and its components (delta(d), delta(p), delta(h)) were determined for series of pharmaceutical excipients by using inverse gas chromatography (IGC). Principal component analysis (PCA) was applied for the selection of the solubility parameters which assure the complete characterization of examined materials. Application of PCA suggests that complete description of examined materials is achieved with four solubility parameters, i.e. delta(2) and Hansen solubility parameters (delta(d), delta(p), delta(h)). Selection of the excipients through PCA of their solubility parameters data can be used for prediction of their behavior in a multi-component system, e.g. for selection of the best materials to form stable pharmaceutical liquid mixtures or stable coating formulation.

Use of genetic profiling in leprosy to discriminate clinical forms of the disease.

Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.

Use of genetic profiling in leprosy to discriminate clinical forms of the disease

Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.