Missense variants in the TNFA epitopes and their effects on interaction with therapeutic antibodies—in silico analysis

Author:

Ahsan Tamim,Sajib Abu Ashfaqur

Abstract

Abstract Background Tumor necrosis factor alpha (TNFA) is an important cytokine that influences multiple biological processes. It is one of the key mediators of acute and chronic systemic inflammatory reactions and plays a central role in several autoimmune diseases. A number of approved monoclonal antibodies (mAbs) are widely used to subside these autoimmune diseases. However, there is a high rate of non-responsiveness to treatments with these mAbs. Therefore, it is important to be able to predict responses of the patients in an individualistic manner to these therapeutic antibodies before administration. In the present study, we used in silico tools to explore the effects of missense variants in the respective epitopes of four therapeutic anti-TNFA mAbs—adalimumab (ADA), certolizumab pegol (CZP), golimumab (GLM), and infliximab (IFX)—on their interactions with TNFA. Results The binding affinities of CZP and ADA to corresponding epitopes appear to be reduced by four (TNFAR131Q, TNFAE135G, TNFAR138Q, and TNFAR138W) and two (TNFAG66C and TNFAG66S) variants, respectively. The binding of GLM and IFX appears to be affected by TNFAR141S and TNFAR138W, respectively. TNFAG66C and TNFAG66S may be associated with autoimmune diseases, whereas TNFAE135G, TNFAR138W, and TNFAR141S may be pathogenic per se. Conclusion These variants may contribute to the observed inter-individual variability in response to anti-TNFA mAbs treatments and be used as markers to predict responses, and thus optimize therapeutic benefits to the patients.

Publisher

Springer Science and Business Media LLC

Subject

Genetics,Biotechnology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3