Tan Wenfeng, Wang Fang, Guo Dunming, Ke Yao, Shen Youxuan, Lv Chengyin, Zhang Miaojia
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Int J Rheum Dis. 2016 May;19(5):482-9. doi: 10.1111/1756-185X.12380. Epub 2014 May 26.
We previously found, using microarray, haptoglobin (HP) expression signal was 5.1-fold increased in peripheral blood mononuclear cells (PBMCs) from methotrexate (MTX)-resistant rheumatoid arthritis (RA) patients.
To investigate whether serum levels of HP are associated with the response of 12 weeks MTX therapy in recent-onset RA patients.
Sixty-nine active RA patients with recent onset (< 24 months) were treated with MTX. Clinical variables, levels of HP messenger RNA (mRNA) in PBMCs and HP serum levels were tested at week 0 and week 12.
After 12 weeks of MTX treatment, 34.7% of RA patients were categorized as responders according to European League Against Rheumatism (EULAR) response criteria (Week 12 Disease Activity Score of 28 joints [DAS-28] ≤ 3.2 and decrease > 1.2) and all others (65.2%) were defined as non-responders. The baseline HP mRNA in PBMCs from non-responders is significantly higher than those in responders (P < 0.05). Similar to mRNA expression, non-responders showed significantly elevated serum HP levels at baseline (369.9 ± 159.8 mg/dL) compared to those in responders (255.3 ± 143.9 mg/dL) (P = 0.01). Serum HP levels were decreased significantly from 255.3 ± 143.9 mg/dL at baseline to 186.4 ± 108.5 mg/dL at week 12 (P = 0.04) in responders, but remained at high levels in non-responders.
High serum levels of HP at baseline are associated with inadequate response of 12 weeks MTX treatment in recent-onset RA patients. Further replication studies in larger samples are needed to validate HP as a potential predictive biomarker for response to MTX therapy in RA.
我们之前使用微阵列技术发现，甲氨蝶呤（MTX）耐药的类风湿关节炎（RA）患者外周血单个核细胞（PBMC）中的触珠蛋白（HP）表达信号增加了5.1倍。
探讨血清HP水平是否与近期发病的RA患者接受12周MTX治疗的反应相关。
69例近期发病（<24个月）的活动性RA患者接受MTX治疗。在第0周和第12周检测临床变量、PBMC中HP信使核糖核酸（mRNA）水平和血清HP水平。
MTX治疗12周后，根据欧洲抗风湿病联盟（EULAR）反应标准，34.7%的RA患者被归类为反应者（28个关节的第12周疾病活动评分[DAS-28]≤3.2且降低>1.2），所有其他患者（65.2%）被定义为无反应者。无反应者PBMC中的基线HP mRNA显著高于反应者（P<0.05）。与mRNA表达相似，无反应者在基线时的血清HP水平（369.9±159.8mg/dL）显著高于反应者（255.3±143.9mg/dL）（P=0.01）。反应者的血清HP水平从基线时的255.3±143.9mg/dL显著降至第12周时的186.4±108.5mg/dL（P=0.04），但无反应者仍保持在高水平。
基线时血清HP水平高与近期发病的RA患者接受12周MTX治疗反应不足相关。需要在更大样本中进行进一步的重复研究，以验证HP作为RA患者对MTX治疗反应的潜在预测生物标志物。
