Related Experiment Videos

Gene profiling predicts rheumatoid arthritis responsiveness to IL-1Ra (anakinra)

Carine Bansard1, Thierry Lequerré, Céline Derambure

  • 1Department of Rheumatology, University of Rouen, 76031 Rouen Cedex, France.

Rheumatology (Oxford, England)
|November 10, 2010
PubMed
Abstract

Insights

Predicting rheumatoid arthritis treatment response is crucial. Gene profiling of peripheral blood mononuclear cells can identify patients likely to respond to anakinra and methotrexate combination therapy.

Area of Science:

  • Rheumatology
  • Molecular Biology
  • Genetics

Background:

  • Rheumatoid arthritis (RA) treatment with biologics has a significant non-response rate (30-40%) in methotrexate-resistant patients.
  • Optimizing biologic selection is essential for improving patient outcomes.

Purpose of the Study:

  • To predict responsiveness to the combination therapy of anakinra and methotrexate (MTX) using peripheral blood mononuclear cell gene profiling.
  • To optimize treatment choices for RA patients who are resistant to MTX.

Main Methods:

  • Thirty-two RA patients receiving anakinra (100 mg/day subcutaneously) and MTX were studied.
  • Responders were defined as those with a decrease in Disease Activity Score-28 (DAS-28) of ≥1.2 at 3 months.
  • Pre-treatment peripheral blood mononuclear cell gene expression profiling was performed using microarrays.

Main Results:

  • A set of 52 differentially expressed mRNAs was identified, capable of separating responders from non-responders via hierarchical clustering.
  • Quantitative RT-PCR validation of seven key transcripts accurately classified 15 of 18 additional patients (87.5% specificity, 77.8% negative-predictive value for responders).
  • A significant portion (56%) of the identified genes were associated with Interleukin-1 beta (IL-1β).

Conclusions:

  • A predictive gene expression profile for anakinra-MTX response was developed using a non-invasive method.
  • This profile, after further validation, could be widely implemented for selecting RA patients likely to benefit from this combination therapy.
  • The study provides a potential tool for personalized medicine in RA treatment.

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...