Transcriptional profiling of leukocytes from rheumatoid arthritis patients before and after anti-tumor necrosis factor therapy: A comparison of anti-nuclear antibody positive and negative subsets

Laurie S. Davis, Andreas M. Reimold

Research output: Contribution to journalArticle

Abstract

Anti-nuclear antibodies (ANAs) may be induced in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor (TNF) therapy with TNF inhibitors (TNFi), etanercept, infliximab or adalimumab. In the present study, 11 patients who were TNFi drug naive were started on TNFi at a time of high disease activity. Of these, all cases were positive for rheumatoid factor and 9 cases tested were positive for anti-citrullinated peptide (anti-CCP) antibodies prior to TNFi treatment. Peripheral blood mononuclear cells (PBMCs) and serum were collected from all patients before and after TNFi therapy. Serum was assayed for ANAs over time. Total cellular RNA was extracted from PBMCs and assessed using Illumina arrays. Gene expression profiles were examined for alterations in key effector pathways. After 3 or more months on TNFi, 6 patients converted to ANA-positivity. Analysis of transcripts from patients with RA who converted to ANA-positivity after 3 months on TNFi identified complex gene expression profiles that reflected a reduction in cell adhesion, cell stress and lipid metabolism transcripts. In summary, unique transcriptional profiles in PBMCs from patients with RA were observed after TNFi therapy. This pilot study suggests that transcriptional profiling is a precise method of measuring the impact of TNFi therapies and reveals novel pathways that likely influence the immune response.

Original languageEnglish (US)
Pages (from-to)2183-2192
Number of pages10
JournalExperimental and Therapeutic Medicine
Volume13
Issue number5
DOIs
StatePublished - May 1 2017

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Anti-Idiotypic Antibodies
Rheumatoid Arthritis
Leukocytes
Tumor Necrosis Factor-alpha
Blood Cells
Transcriptome
Therapeutics
Rheumatoid Factor
Serum
Lipid Metabolism
Cell Adhesion
RNA
Pharmaceutical Preparations

Keywords

  • Anti-nuclear antibody
  • Anti-tumor necrosis factor therapy
  • Rheumatoid arthritis
  • Transcriptional profiling

ASJC Scopus subject areas

  • Immunology and Microbiology (miscellaneous)
  • Cancer Research

Cite this

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title = "Transcriptional profiling of leukocytes from rheumatoid arthritis patients before and after anti-tumor necrosis factor therapy: A comparison of anti-nuclear antibody positive and negative subsets",
abstract = "Anti-nuclear antibodies (ANAs) may be induced in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor (TNF) therapy with TNF inhibitors (TNFi), etanercept, infliximab or adalimumab. In the present study, 11 patients who were TNFi drug naive were started on TNFi at a time of high disease activity. Of these, all cases were positive for rheumatoid factor and 9 cases tested were positive for anti-citrullinated peptide (anti-CCP) antibodies prior to TNFi treatment. Peripheral blood mononuclear cells (PBMCs) and serum were collected from all patients before and after TNFi therapy. Serum was assayed for ANAs over time. Total cellular RNA was extracted from PBMCs and assessed using Illumina arrays. Gene expression profiles were examined for alterations in key effector pathways. After 3 or more months on TNFi, 6 patients converted to ANA-positivity. Analysis of transcripts from patients with RA who converted to ANA-positivity after 3 months on TNFi identified complex gene expression profiles that reflected a reduction in cell adhesion, cell stress and lipid metabolism transcripts. In summary, unique transcriptional profiles in PBMCs from patients with RA were observed after TNFi therapy. This pilot study suggests that transcriptional profiling is a precise method of measuring the impact of TNFi therapies and reveals novel pathways that likely influence the immune response.",
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