Genetic Polymorphisms at TNF-Alpha Receptors Associated some Autoimmune Diseases and Response of Anti-TNF Biologics: Review

Abstract

Some genetic factors are not only involved in some autoimmune diseases but also interfere with their treatment, Such as Crohn's disease (CD), Rheumatoid Arthritis (RA), Psoriasis (PS) and ankylosing spondylitis (AS). Tumor Necrosis Factor (TNF) is a most important pro-inflammatory cytokine, which has been recognized as a main factor that participates in the pathogenesis and development of autoimmune disorders. Therefore, TNF could be a prospective target for treating these disorders, and many anti-TNF were developed to treat these disorders. Although the high efficacy of many anti-TNF biologic medications, the Patients' clinical responses to the autoimmune treatment showed significant heterogeneity. The TNF receptors classified into two TNF receptors, namely TNFR1 and TNFR2. These receptors belong to two distinct superfamilies: the TNF-superfamily of ligands (TNFSF) consisting of 19 ligands and the TNF receptor superfamily (TNFRSF) comprising 29 receptors. This review aims to provide an overview of the impact of genetic polymorphism on TNF alpha receptors on the response of patients with some auto immune diseases to anti-TNF biologics. Several single nucleotide polymorphisms (SNPs) recorded in the TNFRs gene on various immune system cells may affect the lower corresponding TNFRs gene expression. The present review summarized the studies that highlighted the role of heterogeneity in varying the response of the auto immune patients. Many researchers indicated SNPs' have an effect on the response of autoimmune patients to treatment with anti-TNF biologic medications, while other studies did not find a correlation. In conclusion, TNF is involved in several diseases such as CD, RA, PS and AS; there was a link between TNFRs polymorphism and non-responsiveness to anti-TNF-α medications.