Gastroenterology Department, Santa Lucía General University Hospital (HGUSL), C/ Mezquita sn, 30202 Cartagena, Spain.
Pathology Department, HGUSL, Cartagena, Spain.
Int J Med Sci. 2018 Jan 1;15(1):10-15. doi: 10.7150/ijms.22812. eCollection 2018.
The production of anti-drug antibodies (ADAs) against IgG monoclonal antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG complexes, we hypothesised that a polymorphism in (V158F; rs396991) gene could be involved in anti-TNF ADA generation and treatment resistance.
A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum level of both anti-TNFs (infliximab or adalimumab) and ADA against them were measured.
No significant differences were observed between ADA occurrence or V158F genotype and type of disease or the kind of anti-TNF administrated. Interestingly, VV genotype correlated with patients producing ADA (VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of this event after multivariate analysis. Moreover, VV genotype also correlated with those patients receiving anti-TNF dose intensification (p=0.03).
V158F polymorphism seems to be associated with ADA production against mAbs and it could be taken into account when considering the dose and type of anti-TNF in IBD patients.
针对肿瘤坏死因子 (TNF) 的 IgG 单克隆抗体 (mAb) 产生的抗药物抗体 (ADA) 是导致炎症性肠病 (IBD) 患者（如克罗恩病 (CD) 和溃疡性结肠炎 (UC)）对 TNF mAb 失去应答的一个重要原因。由于 IgG Fc 段的受体 (FCGRs) 参与 IgG 复合物的降解，我们假设基因 (V158F; rs396991) 中的一个多态性可能与抗 TNF ADA 的产生和治疗抵抗有关。
对 103 名 IBD 患者（80 名 CD，23 名 UC）进行了基因分型，并测量了他们的血清中抗 TNF 药物（英夫利昔单抗或阿达木单抗）和 ADA 的水平。
未观察到 ADA 发生或 V158F 基因型与疾病类型或所使用的抗 TNF 药物之间存在显著差异。有趣的是，VV 基因型与产生 ADA 的患者相关（VV：37.5% 比 FV：10.6% 或 FF：5%；p=0.004），并且在多变量分析后是这种事件的独立预测因素。此外，VV 基因型也与那些需要增加抗 TNF 剂量的患者相关（p=0.03）。
V158F 多态性似乎与针对 mAb 的 ADA 产生有关，在考虑 IBD 患者的抗 TNF 药物剂量和类型时可以考虑这一点。
