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Gene expression patterns associated with multidrug therapy in multibacillary leprosy.

Helen Ferreira1, Thyago Leal-Calvo1, Mayara Abud Mendes1

  • 1Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.

Frontiers in Cellular and Infection Microbiology
|August 8, 2022
PubMed
Summary
This summary is machine-generated.

Multidrug therapy (MDT) for leprosy shows varied outcomes. Gene expression analysis in multibacillary leprosy patients reveals distinct host immune and lipid metabolism signatures linked to treatment response.

Keywords:
bacillary loadgene signaturelipid metabolismmultibacillary leprosymultidrug therapy

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Area of Science:

  • Immunology
  • Genetics
  • Infectious Diseases

Background:

  • Multidrug therapy (MDT) is standard for leprosy but doesn't prevent reactions, disability, or relapse.
  • Multibacillary (MB) leprosy patients exhibit impaired cellular immunity against Mycobacterium leprae, leading to slow bacillary clearance.
  • Incomplete bacillary index reduction after MDT is common in MB patients.

Purpose of the Study:

  • To investigate host gene expression patterns in MB leprosy patients before and after MDT.
  • To identify gene expression differences between patients with varying responses to MDT.
  • To elucidate gene signatures associated with MDT treatment outcomes.

Main Methods:

  • Recruited MB leprosy patients at baseline and after 12 months of MDT.
  • Stratified patients based on bacillary index (BI) reduction (≥1 log reduction defined responders).
  • Analyzed host gene expression in skin biopsies using RNA sequencing.

Main Results:

  • Responders showed reduced expression of lipid metabolism, inflammatory, and immune response genes post-MDT.
  • Non-responders or low-BI-reduction patients had higher pre-MDT expression of specific genes (e.g., CDH19, TMPRSS4).
  • MDT modulated immune and lipid metabolism pathways, with higher CYP11A1 (cholesterol metabolism) expression in poorer responders.

Conclusions:

  • Gene expression profiles correlate with MDT treatment response in MB leprosy.
  • Identified specific host genes and pathways (immune response, lipid metabolism) linked to MDT outcomes.
  • Findings contribute to understanding gene signatures influencing leprosy treatment efficacy.