Related Experiment Video

Updated: Apr 15, 2026

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
07:37

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice

Published on: June 6, 2025

1.5K

TNF-α gene polymorphisms and juvenile idiopathic arthritis: Influence on disease outcome and therapeutic response

Alessandra Scardapane1, Rossella Ferrante2, Manuela Nozzi1

  • 1Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy.

Seminars in Arthritis and Rheumatism
|April 4, 2015
PubMed

Insights

Certain tumor necrosis factor-alpha (TNF-α) gene variations are linked to worse outcomes in juvenile idiopathic arthritis (JIA). Patients with specific TNF-α genotypes show reduced response to anti-TNF-α therapies.

Area of Science:

  • Immunogenetics
  • Rheumatology
  • Pediatric Autoimmunity

Background:

  • Juvenile idiopathic arthritis (JIA) is a complex autoimmune disease with significant genetic influences.
  • Tumor necrosis factor-alpha (TNF-α) is a key pro-inflammatory cytokine implicated in JIA pathogenesis.
  • Understanding the genetic contribution of TNF-α polymorphisms may offer insights into disease course and treatment efficacy.

Purpose of the Study:

  • To investigate the association between TNF-α gene promoter polymorphisms and the clinical manifestations and treatment response in Caucasian JIA patients.
  • To identify specific genetic markers that predict disease activity and response to biologic therapies in JIA.

Main Methods:

  • Genotyping of TNF-α promoter polymorphisms (-163, -244, -238, -376, -308) in 74 JIA patients and 77 healthy controls.
  • Analysis of genotype frequencies and their correlation with disease phenotypes, activity scores, and response to anti-TNF-α therapy over 12 months.

Main Results:

  • No significant differences in TNF-α -238 and -308 G/A genotype prevalence between JIA patients and controls.
  • JIA patients with TNF-α -308 GG genotype exhibited significantly lower disease activity at 6 and 12 months compared to GA/AA genotypes.
  • Carriers of -238/-308 GG genotypes showed greater reduction in disease activity. Patients with -308 AA genotype had higher disease activity after 12 months of biologic therapy.

Conclusions:

  • TNF-α gene polymorphisms at positions -308 (GA/AA) and -238 (GA) are associated with a poorer prognosis in JIA.
  • These specific TNF-α genotypes may predict a diminished response to anti-TNF-α biologic therapies in JIA patients.
Abstract

Keywords:
Biological therapyGene polymorphismsJuvenile idiopathic arthritisTumor necrosis factor-α

More Related Videos

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene07:00

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene

Published on: April 1, 2019

10.6K
Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes11:52

Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes

Published on: January 27, 2023

4.9K

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...
3.5K
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...
14.2K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
71
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.8K
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...
804
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

2.6K