In a nutshell
This paper studies the effect of killer cell immunoglobulin-like receptor genes on methotrexate (Trexall) treatment.
Some background
Rheumatoid arthritis is an inflammatory disorder involving the immune system. Natural killer cells are part of the immune system and have been reported to contribute to rheumatoid arthritis. Natural killer cell receptors (proteins on the surface of the cell that cause signalling within the cell to occur in response to outside stimulation) are produced from killer cell immunoglobulin-like receptor (KIR; type of receptor) genes. KIR genes can affect the activity of natural killer cells which can subsequently affects one's susceptibility to rheumatoid arthritis.
Methotrexate (Trexall) treats rheumatoid arthritis by suppressing the immune response. However, it is not suitable for all patients and typically only 50-60% of patients respond to methotrexate treatment. The authors studied whether KIR genes influence the effectiveness of methotrexate.
Methods & findings
312 patients (253 females, 59 males) with rheumatoid arthritis were studied. All patients underwent laboratory tests and screening to identify the presence of the KIR genes. X-rays of chest, hands and feet were obtained. Subjects were also evaluated by physical examination.
All patients underwent standard methotrexate treatment. No patients received disease-modifying antirheumatic drugs. Patients were classified into two groups based on their disease activity score (DAS28 a measure of disease activity in 28 joints): a good methotrexate response group (179 patients) and a poor methotrexate response group (133 patients).
Overall, 57.3% of patients responded to methotrexate treatment. The frequencies of the KIR genes were compared between good response group and poor response group. It was observed that only one KIR gene (full length KIR2DS4 gene) had an effect on the response to methotrexate. Patients possessing this KIR 2DS4 gene had a lower chance of responding to methotrexate treatment.
For patients with both erosive disease and rheumatoid factor positive status (presence of this protein increases risk of rheumatoid arthritis), patients with KIR2DS4 gene had a lower chance of responding to methotrexate treatment than those without KIR2DS4 gene. 36.2% of those with the gene had a good response compared to 43.6% of those without the gene. For patients without both erosive disease and rheumatoid factor positive status, those with KIR2DS4 gene had a lower chance of responding to methotrexate therapy than those without KIR2DS4 gene. 75% of those with the gene had a good response compared to 88% of those without the gene. Age of diagnosis had very little influence on KIR2DS4 gene effect.
The bottom line
The authors concluded that the presence of the full-length KIR2DS4 gene reduces the chance that patients with rheumatoid arthritis will respond to methotrexate treatment.
What’s next?
Discuss with your doctor the potential of evaluating the status of your KIR2DS4 gene if considering or not responding to methotrexate treatment.
Published By :
BMC musculoskeletal disorders
Date :
Jul 28, 2014
