Dataset Information

Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.

ABSTRACT: Leprosy reactions are responsible for incapacities in leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of multibacillary leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of TLR2 and MLST8. The autophagy impairment in T1R group was associated with increased expression of NLRP3, caspase-1 (p10) and IL-1? production. In addition, analysis of IL-1? production in serum from multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1? at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. In vitro analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in Mycobacterium leprae-stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1? and IL-6 production. Together, our data suggest an important role for autophagy in multibacillary leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.

SUBMITTER: de Mattos Barbosa MG

PROVIDER: S-EPMC5994478 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.

de Mattos Barbosa Mayara Garcia MG de Andrade Silva Bruno Jorge BJ Assis Tayná Quintella TQ da Silva Prata Rhana Berto RB Ferreira Helen H Andrade Priscila Ribeiro PR da Paixão de Oliveira Jéssica Araújo JA Sperandio da Silva Gilberto Marcelo GM da Costa Nery José Augusto JA Sarno Euzenir Nunes EN Pinheiro Roberta Olmo RO

Frontiers in immunology 20180604

Leprosy reactions are responsible for incapacities in leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, multibacillary patients were recr ...[more]

PMID: 29915584

Similar Datasets

Project description:BackgroundLeprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy.Methodology/findingsWe followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL.ConclusionsDifferential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions.

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.

Dataset Information

Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.

Publications

Autophagy Impairment Is Associated With Increased Inflammasome Activation and Reversal Reaction Development in Multibacillary Leprosy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets