德国研究人员最新研发出一种新的基因检测方法,能够提前判断“抗肿瘤坏死因子疗法”对患者的疗效,从而避免不适用这种疗法的类风湿性关节炎患者受到该疗法副作用的影响。
德国沙里泰大学医院27日发表公报说,一种名叫肿瘤坏死因子的蛋白质会导致类风湿性关节炎等疾病,“抗肿瘤坏死因子疗法”通过阻断这种蛋白质来消除炎症,但这种疗法却不适用于所有患者,而且有一定副作用。
该院研究人员利用逆转录聚合酶链反应(RT-PCR)技术研究了27名类风湿性关节炎患者的血液,发现患者体内一种名为CD11c的基因表达强度与“抗肿瘤坏死因子疗法”的疗效有显着关系。
研究显示,这种疗法只在CD11c基因表达较强的患者身上有效,而这类患者约占所有病例的60%。
研究人员说,利用新的基因检测法,医生可以提前确定“抗肿瘤坏死因子疗法”是否适合某一患者,避免了不适合此疗法的患者受其副作用影响。研究人员下一步希望将这种检测方法与其他疗法结合,开发出更有效的新疗法。
这一成果发表在最新一期美国《临床药理学与治疗学》双月刊上。(生物谷Bioon.com)
生物谷推荐原文出处:
Clinical Pharmacology & Therapeutics doi:10.1038/clpt.2009.244
CD11c as a Transcriptional Biomarker to Predict Response to Anti-TNF Monotherapy With Adalimumab in Patients With Rheumatoid Arthritis
B Stuhlmüller, T H?upl, M M Hernandez, A Grützkau, R-J Kuban, N Tandon, J W Voss, J Salfeld, R W Kinne and G R Burmester
We performed transcription profiling using monocytes to identify predictive markers of response to anti–tumor necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). Several potential predictors of response were identified, including CD11c. Validation in samples from independent cohorts (total of n = 27 patients) using reverse transcription–PCR confirmed increased expression of CD11c in responders to adalimumab (100% sensitivity; 91.7% specificity, power 99.6%; α = 0.01). Pretherapy CD11c levels significantly correlated with the response criteria as defined by the American College of Rheumatology (ACR) (r = 0.656, P < 0.0001). However, CD11c was neither predictive of response to methotrexate (MTX) alone (n = 34) nor to MTX in combination with adalimumab (n = 16). Clinical responders revealed a reset to a normal expression pattern of resident/inflammatory monocyte markers, which was absent in nonresponders. Therefore, an analysis of key cell types identifies potentially predictive biomarkers that may help to restrict the use of adalimumab to therapy responders. Larger studies, including studies of monotherapy with other drugs, are now needed to confirm and validate the specificity of CD11c for anti-TNF biologics.