The use of an interferon-gamma release assay as a biomarker of response to anti-TNF-alpha treatment.
Tumor necrosis factor alpha (TNF-α) is a pleiotropic cytokine that plays a central role in the immune system functioning and in the pathogenesis of rheumatoid arthritis (RA). TNF-α inhibition has been demonstrated effective to treat RA; however, response to anti-TNF-α therapies is heterogeneous, with roughly one-third of patients not achieving disease control. Identification of a biological marker to assess the effectiveness of TNF-α inhibition may help to discriminate patients with a reduced response to anti-TNF-α agents. The aim of this study was to assess whether anti-TNF-α treatment was able to modify the cytokine network interfering with interferon gamma (INFγ) release after phytohemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMCs) from RA patients, according to disease activity. We found that RA patients with active disease had low release of INFγ after PHA stimulation, but anti-TNF-α agents were able to modify INFγ production. In anti-TNF-α responders, we observed a higher release of INFγ, achieving levels comparable with those seen in healthy subjects. The ability of PBMCs from RA patients to release INFγ may serve as a biomarker of disease activity and response to anti-TNF-α. Larger studies are needed to validate these data.
Internal Medicine Unit and Outpatient clinic of Rheumatology, "N. Melli" Hospital of San Pietro V.co (BR), Brindisi, 72027, Italy.
Fabio
F
Cacciapaglia
Francesca
F
Buzzulini
Luisa
L
Arcarese
Elisabetta
E
Ferraro
Antonella
A
Afeltra
D000068879:Adalimumab; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism*; D059425:Interferon-gamma Release Tests; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007074:Immunoglobulin G; D010835:Phytohemagglutinins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000068879:Adalimumab; D000068800:Etanercept
anti-tumor necrosis factor (TNF) agent; biomarker; interferon gamma release assay; rheumatoid arthritis