Assessing the Role of DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio in Rheumatoid Arthritis.
Assessing the Role of DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio in Rheumatoid Arthritis.
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DOI：
10.1155/2018/2624981
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发表时间：
2018
影响因子：
4.1
通讯作者：
Relton CL
中科院分区：
文献类型：
--
作者：
Ambatipudi S;Sharp GC;Clarke SLN;Plant D;Tobias JH;Evans DM;Barton A;Relton CL
类风湿关节炎（RA）是一种慢性全身性炎症（SI）疾病。在本研究中，我们使用了四个数据集来探讨甲基化衍生的中性粒细胞与淋巴细胞比值（mdNLR）是否可能是新发、未治疗以及已治疗的常见类风湿关节炎病例中全身性炎症的标志物，和/或肿瘤坏死因子抑制剂（TNFi）依那西普治疗反应的标志物。mdNLR与成为新发类风湿关节炎病例的几率增加相关（比值比 = 2.32，95%置信区间 = 1.95 - 2.80，P < 2×10⁻¹⁶），并且在区分新发类风湿关节炎病例和对照方面，与协变量（年龄、性别和吸烟状况）相比表现更好。在未治疗的临床前期类风湿关节炎病例和对照中，调整批次后，基线时的mdNLR与后期类风湿关节炎的诊断相关（比值比 = 4.30，95%置信区间 = 1.52 - 21.71，P = 0.029），尽管在批次校正前未观察到相关性。当常见类风湿关节炎病例接受治疗时，批次校正前后的样本中mdNLR均无相关性（比值比 = 0.34，95%置信区间 = 0.05 - 1.82，P = 0.23），并且mdNLR与依那西普的治疗反应无关（比值比 = 1.10，95%置信区间 = 0.75 - 1.68，P = 0.64）。我们的结果表明，通过DNA甲基化数据测量的全身性炎症可指示类风湿关节炎的近期发病。尽管临床前期类风湿关节炎与mdNLR相关，但临床前期类风湿关节炎病例和对照之间的平均mdNLR无差异。如果类风湿关节炎已开始治疗，mdNLR与类风湿关节炎病例状态无关，且与治疗反应无关。未来，在没有新鲜采集的血液样本的情况下，mdNLR估计值可能作为一种有价值的研究工具来可靠地估计全身性炎症。
Rheumatoid arthritis (RA) is a disease of chronic systemic inflammation (SI). In the present study, we used four datasets to explore whether methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) might be a marker of SI in new onset, untreated, and treated prevalent RA cases and/or a marker of treatment response to the tumour necrosis factor inhibitor (TNFi) etanercept. mdNLR was associated with increased odds of being a new onset RA case (OR = 2.32, 95% CI = 1.95–2.80, P < 2 × 10−16) and performed better in distinguishing new onset RA cases from controls compared to covariates: age, gender, and smoking status. In untreated preclinical RA cases and controls, mdNLR at baseline was associated with diagnosis of RA in later life after adjusting for batch (OR = 4.30, 95% CI = 1.52–21.71, P = 0.029) although no association was observed before batch correction. When prevalent RA cases were treated, there was no association with mdNLR in samples before and after batch correction (OR = 0.34, 95% CI = 0.05–1.82, P = 0.23), and mdNLR was not associated with treatment response to etanercept (OR = 1.10, 95% CI = 0.75–1.68, P = 0.64). Our results indicate that SI measured by DNA methylation data is indicative of the recent onset of RA. Although preclinical RA was associated with mdNLR, there was no difference in the mean mdNLR between preclinical RA cases and controls. mdNLR was not associated with RA case status if treatment for RA has commenced, and it is not associated with treatment response. In the future, mdNLR estimates may be used as a valuable research tool to reliably estimate SI in the absence of freshly collected blood samples.
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