Genome-wide gene expression profiling reveals unsuspected molecular alterations in pemphigus foliaceus

Authors

  • Danielle Malheiros,

    1. Human Molecular Genetics Laboratory, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil
    Search for more papers by this author
  • Rodrigo A. Panepucci,

    1. Haematology Division and Centre for Cell-Based Therapy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
    Search for more papers by this author
  • Ana M. Roselino,

    1. Division of Dermatology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
    Search for more papers by this author
  • Amélia G. Araújo,

    1. Haematology Division and Centre for Cell-Based Therapy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
    Search for more papers by this author
  • Marco A. Zago,

    1. Haematology Division and Centre for Cell-Based Therapy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
    Search for more papers by this author
  • Maria Luiza Petzl-Erler

    Corresponding author
    1. Human Molecular Genetics Laboratory, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil
    • Correspondence: Maria Luiza Petzl-Erler, Department of Genetics, Federal University of Paraná Caixa Postal 19071, 81531-980 Curitiba, Brazil.

      Email: perler@ufpr.br

      Senior author: Maria Luiza Petzl-Erler

    Search for more papers by this author

Summary

Pemphigus foliaceus (PF) is a complex autoimmune disease characterized by bullous skin lesions and the presence of antibodies against desmoglein 1. In this study we sought to contribute to a better understanding of the molecular processes in endemic PF, as the identification of factors that participate in the pathogenesis is a prerequisite for understanding its biological basis and may lead to novel therapeutic interventions. CD4+ T lymphocytes are central to the development of the disease. Therefore, we compared genome-wide gene expression profiles of peripheral CD4+ T cells of various PF patient subgroups with each other and with that of healthy individuals. The patient sample was subdivided into three groups: untreated patients with the generalized form of the disease, patients submitted to immunosuppressive treatment, and patients with the localized form of the disease. Comparisons between different subgroups resulted in 135, 54 and 64 genes differentially expressed. These genes are mainly related to lymphocyte adhesion and migration, apoptosis, cellular proliferation, cytotoxicity and antigen presentation. Several of these genes were differentially expressed when comparing lesional and uninvolved skin from the same patient. The chromosomal regions 19q13 and 12p13 concentrate differentially expressed genes and are candidate regions for PF susceptibility genes and disease markers. Our results reveal genes involved in disease severity, potential therapeutic targets and previously unsuspected processes involved in the pathogenesis. Besides, this study adds original information that will contribute to the understanding of PF's pathogenesis and of the still poorly defined in vivo functions of most of these genes.

Ancillary