Department of Rheumatology and Clinical Immunology, Charité University Hospital, Humboldt University of Berlin, Berlin, Germany.
Clin Pharmacol Ther. 2010 Mar;87(3):311-21. doi: 10.1038/clpt.2009.244. Epub 2009 Dec 23.
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%; alpha = 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.
我们通过单核细胞进行转录谱分析，以确定类风湿关节炎 (RA) 患者对肿瘤坏死因子 (anti-TNF) 治疗反应的预测标志物。确定了几个潜在的反应预测因子，包括 CD11c。使用逆转录-PCR 在独立队列的样本中进行验证（总共 27 例患者），证实了对阿达木单抗有反应的患者 CD11c 的表达增加（100%敏感性；91.7%特异性，99.6%功率；alpha = 0.01）。治疗前 CD11c 水平与美国风湿病学会 (ACR) 定义的反应标准显著相关（r = 0.656，P < 0.0001）。然而，CD11c 既不能预测单独使用甲氨蝶呤 (MTX)（n = 34）的反应，也不能预测 MTX 联合阿达木单抗的反应（n = 16）。临床反应者表现出常驻/炎症性单核细胞标志物表达模式的重置，而非反应者则没有这种情况。因此，对关键细胞类型的分析确定了潜在的预测生物标志物，这可能有助于将阿达木单抗的使用限制在治疗反应者。现在需要更大的研究，包括其他药物单药治疗的研究，以确认和验证 CD11c 对 TNF 生物制剂的特异性。
