Investigation of the prognostic value of TNF-α gene polymorphism among patients treated with infliximab, and the effects of infliximab therapy on TNF-α production and apoptosis

Attila Balog, Gergely Klausz, János Gál, T. Molnár, F. Nagy, Imre Ocsovszky, Zsófia Gyulai, Y. Mándi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objectives: Infliximab, a chimeric anti-tumor necrosis factor (TNF) antibody, is highly effective for the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA). Our experiments focused on RA and CD patients receiving infliximab. Since cytokine production is largely determined by genetic factors, the promoter polymorphisms of TNF-α were examined among these patients. Additionally, the changes caused by infliximab in the TNF-α-producing ability and apoptosis of peripheral blood mononuclear cells (PBMCs) were investigated. Methods: The TNF-α genotypes were analyzed by PCR-RFLP. The in vitro TNF-α production of the PBMCs was detected by flow cytometric analysis. The TNF-α concentration in the supernatant was measured by bioassay. Apoptosis was detected by annexin V-fluorescein isothiocyanate labeling. Results and Conclusions: 8 of the 12 nonresponder patients carried the TNF A allele associated with high TNF-α production. We suggest that the determination of TNF polymorphism may help identify more suitable candidates for infliximab treatment. Although in vitro infliximab treatment for 48 h resulted in significant (44.2 ± 1.17%) apoptosis in PBMCs, in ex vivo samples from RA patients who received infliximab, apoptosis was only 13.3 ± 1.6%. Furthermore, infliximab did not result in irreversible inhibition of the TNF-α-producing ability or in the significant apoptosis of PBMCs.

Original languageEnglish
Pages (from-to)274-280
Number of pages7
JournalPathobiology
Volume71
Issue number5
DOIs
Publication statusPublished - 2004

Fingerprint

Polymorphism
Tumor Necrosis Factor-alpha
Genes
Apoptosis
Blood Cells
Blood
Therapeutics
Rheumatoid Arthritis
Crohn Disease
Infliximab
Bioassay
Annexin A5
Fluorescein
Genetic Promoter Regions
Restriction Fragment Length Polymorphisms
Biological Assay
Labeling
Alleles
Genotype
Cytokines

Keywords

  • Apoptosis
  • Crohn's disease
  • Gene polymorphism
  • Infliximab
  • Intracellular cytokine
  • Rheumatoid arthritis
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Biochemistry
  • Immunology and Allergy
  • Cell Biology

Cite this

Investigation of the prognostic value of TNF-α gene polymorphism among patients treated with infliximab, and the effects of infliximab therapy on TNF-α production and apoptosis. / Balog, Attila; Klausz, Gergely; Gál, János; Molnár, T.; Nagy, F.; Ocsovszky, Imre; Gyulai, Zsófia; Mándi, Y.

In: Pathobiology, Vol. 71, No. 5, 2004, p. 274-280.

Research output: Contribution to journalArticle

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AU - Balog, Attila

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AU - Gál, János

AU - Molnár, T.

AU - Nagy, F.

AU - Ocsovszky, Imre

AU - Gyulai, Zsófia

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