Dataset Information

Anti-Lipoarabinomannan-Specific Salivary IgA as Prognostic Marker for Leprosy Reactions in Patients and Cellular Immunity in Contacts.

ABSTRACT: Leprosy causes the most common peripheral neuropathy of infectious etiology, posing an important public health problem worldwide. Understanding the molecular and immunological mechanisms of nerve damage induced by M. leprae is mandatory to develop tools for early diagnosis and preventive measures. The phenolic glycolipid 1 (PGL-1) and lipoarabinomannan (LAM) antigens are major components of the bacterial surface and are implicated on leprosy immunopathogenesis and neural damage. Although the anti-PGL-1 serum IgM is highly used for operational classification of patients, the anti-LAM salivary IgA (sIgA) has not been investigated as diagnostic or prognostic marker in leprosy. Our aim was to assess the presence of anti-LAM sIgA in leprosy patients and their contacts in order to demonstrate whether such expression was associated with leprosy reactions. Distinct patterns of anti-LAM slgA were observed among groups, which were stratified into treatment-naïve patients (116), patients who completed multidrug therapy-MDT (39), household contacts (111), and endemic controls (11). Both anti-LAM sIgA and anti-PGL-I serum IgM presented similar prognostic odds toward leprosy reactions [(odds ratio) OR?=?2.33 and 2.78, respectively]. Furthermore, the anti-LAM sIgA was highly correlated with multibacillary (MB) forms (OR?=?4.15). Contrarily, among contacts the positive anti-LAM sIgA was highly correlated with those with positive Mitsuda test, suggesting that the presence of anti-LAM slgA may act as an indicator of cellular immunity conferred to contacts. Our data suggest that anti-LAM slgA may be used as a tool to monitor patients undergoing treatment to predict reactional episodes and may also be used in contacts to evaluate their cellular immunity without the need of Mitsuda tests.

SUBMITTER: Nahas AA

PROVIDER: S-EPMC5990868 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Anti-Lipoarabinomannan-Specific Salivary IgA as Prognostic Marker for Leprosy Reactions in Patients and Cellular Immunity in Contacts.

Nahas André Alan AA Lima Mayara Ingrid de Sousa MIS Goulart Isabela Maria Bernardes IMB Goulart Luiz Ricardo LR

Frontiers in immunology 20180530

Leprosy causes the most common peripheral neuropathy of infectious etiology, posing an important public health problem worldwide. Understanding the molecular and immunological mechanisms of nerve damage induced by <i>M. leprae</i> is mandatory to develop tools for early diagnosis and preventive measures. The phenolic glycolipid 1 (PGL-1) and lipoarabinomannan (LAM) antigens are major components of the bacterial surface and are implicated on leprosy immunopathogenesis and neural damage. Although ...[more]

PMID: 29904387

Similar Datasets

Project description:ImportanceDespite progress toward reducing global incidence, leprosy control remains a challenge in low- and middle-income countries.ObjectiveTo estimate new case detection rates of leprosy among household contacts of patients with previously diagnosed leprosy and to investigate its associated risk factors.Design, setting, and participantsThis population-based cohort study included families registered in the 100 Million Brazilian Cohort linked with nationwide registries of leprosy; data were collected from January 1, 2007, through December 31, 2014. Household contacts of patients with a previous diagnosis of leprosy from each household unit were followed up from the time of detection of the primary case to the time of detection of a subsequent case or until December 31, 2014. Data analysis was performed from May to December 2018.ExposuresClinical characteristics of the primary case and sociodemographic factors of the household contact.Main outcomes and measuresIncidence of leprosy, estimated as the new case detection rate of leprosy per 100 000 household contacts at risk (person-years at risk). The association between occurrence of a subsequent leprosy case and the exposure risk factors was assessed using multilevel mixed-effects logistic regressions allowing for state- and household-specific random effects.ResultsAmong 42 725 household contacts (22 449 [52.5%] female; mean [SD] age, 22.4 [18.5] years) of 17 876 patients detected with leprosy, the new case detection rate of leprosy was 636.3 (95% CI, 594.4-681.1) per 100 000 person-years at risk overall and 521.9 (95% CI, 466.3-584.1) per 100 000 person-years at risk among children younger than 15 years. Household contacts of patients with multibacillary leprosy had higher odds of developing leprosy (adjusted odds ratio [OR], 1.48; 95% CI, 1.17-1.88), and the odds increased among contacts aged 50 years or older (adjusted OR, 3.11; 95% CI, 2.03-4.76). Leprosy detection was negatively associated with illiterate or preschool educational level (adjusted OR, 0.59; 95% CI, 0.38-0.92). For children, the odds were increased among boys (adjusted OR, 1.70; 95% CI, 1.20-2.42).Conclusions and relevanceThe findings in this Brazilian population-based cohort study suggest that the household contacts of patients with leprosy may have increased risk of leprosy, especially in households with existing multibacillary cases and older contacts. Public health interventions, such as contact screening, that specifically target this population appear to be needed.

Project description:BackgroundThis study aimed to evaluate the risk factors associated with developing leprosy among the contacts of newly-diagnosed leprosy patients.Methodology/principal findingsA total of 6,158 contacts and 1,201 leprosy patients of the cohort who were diagnosed and treated at the Leprosy Laboratory of Fiocruz from 1987 to 2007 were included. The contact variables analyzed were sex; age; educational and income levels; blood relationship, if any, to the index case; household or non-household relationship; length of time of close association with the index case; receipt of bacillus Calmette-Guérin (BGG) vaccine and presence of BCG scar. Index cases variables included sex, age, educational level, family size, bacillary load, and disability grade. Multilevel logistic regression with random intercept was applied. Among the co-prevalent cases, the leprosy-related variables that remained associated with leprosy included type of household contact, [odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.02, 1.73] and consanguinity with the index case, (OR = 1.89, 95% CI: 1.42-2.51). With respect to the index case variables, the factors associated with leprosy among contacts included up to 4 years of schooling and 4 to 10 years of schooling (OR = 2.72, 95% CI: 1.54-4.79 and 2.40, 95% CI: 1.30-4.42, respectively) and bacillary load, which increased the chance of leprosy among multibacillary contacts for those with a bacillary index of one to three and greater than three (OR = 1.79, 95% CI: 1.19-2.17 and OR: 4.07-95% CI: 2.73, 6.09), respectively. Among incident cases, household exposure was associated with leprosy (OR = 1.96, 95% CI: 1.29-2.98), compared with non-household exposure. Among the index case risk factors, an elevated bacillary load was the only variable associated with leprosy in the contacts.Conclusions/significanceBiological and social factors appear to be associated with leprosy among co-prevalent cases, whereas the factors related to the infectious load and proximity with the index case were associated with leprosy that appeared in the incident cases during follow-up.

Project description:Background: Reactions in Leprosy are immune exacerbations that cause debilitating consequences like nerve damage and permanent deformities. Prediction of these reactional states using appropriate biomarkers would enable early treatment interventions to prevent nerve function impairment. The current study investigated whole transcriptomic expression profiles of Mycobacterium leprae (M. leprae) that differentiate leprosy cases in type 2 (Erythema Nodosum Leprosum) reactions with those without reactions in host skin tissue derived RNA. Methods: Post clinical examination, excisional skin biopsy specimens were collected from skin lesions of subjects with and without type 2 reaction. Total RNA was extracted following the Trizol protocol and bacterial RNA was enriched in the samples. A 2 x 400K gene expression array (whole genome tiling array) was designed with the probes having 60-mer oligonucleotides tiling every 10bp of the genome sequence of M. leprae (NC_011896.1). The array comprised 420288 features which include probes and Agilent controls. The quality of RNA was estimated using BioAnalyzer (Agilent Technologies) followed by labelling, reverse transcription, amplification and hybridization to the arrays. The hybridized slides were scanned on a G2600D scanner (Agilent Technologies). The data thus acquired is analysed using GeneSpring GX Version 12.1 software. Data was normalized and fold difference in expression was noted from 359,922 probes which include sense and antisense orientations of 179,961 probes. The differentially expressing M. leprae genomic regions between type 2 reactions and non reactional cases were noted. Results: Considering a statistical cut-off value of 0.6 for fold difference in expression between the test and the control samples, a set of 107 genes indicated statistically significant up-regulation with volcano plot p-values less than 0.05. Functional characterization revealed higher-expression of genes encoding transmembrane proteins (12), regulatory proteins (9), fatty acid biosynthesis (6), amino acid metabolism (13), nucleic acid metabolism (7), DNA replication and repair (7), Secretory proteins (2) Krebs Cycle (1), Glycolysis (1), Drug Efflux Protein (1),Stress Response Protein (1), Energy Metabolism (2), Pantothenate biosynthesis (1), Metalloproteins (3), Hydrolases (1) and Hypothetical Proteins (40). Additionally there are 157 genes that are down regulated in cases with reaction. Conclusion: Differential expression of genes in the human skin biopsy specimens among leprosy cases with type 2 reaction in contrast to those without reaction suggests the role of pathogen associated gene expression triggers with the aetiology of these reactions. As most of the transmembrane and cell wall proteins possess epitope and surface exposed domains, higher expression levels of genes encoding these proteins may have a possible role in enhancing host immune responses characteristic of type 2 reactions in leprosy.

Dataset Information

Anti-Lipoarabinomannan-Specific Salivary IgA as Prognostic Marker for Leprosy Reactions in Patients and Cellular Immunity in Contacts.

Publications

Anti-Lipoarabinomannan-Specific Salivary IgA as Prognostic Marker for Leprosy Reactions in Patients and Cellular Immunity in Contacts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets