Exploring Pharmacogenetic Variants for Predicting Response to Anti-TNF Therapy in Autoimmune Diseases: a Meta-Analysis

Abstract

Aim: The aim of this study is to explore how SNPs may affect the response to anti-TNF-α therapy in the major autoimmune diseases, such as psoriasis, rheumatoid arthritis, inflammatory bowel diseases and Spondyloarthritis. Methodology: We conducted a systematic overview on the field, by assessing all studies that examined the association between polymorphisms and response to anti-TNF-α therapy in participants of European descent. Results: In total, six independent SNPs located in FCGR2A, FCGR3A, TNF-α and TNFRSF1B genes were significantly associated with response to TNF-α blockers, found mainly in disease-subgroup analyses. Conclusion: No common pharmacogenetic variant was identified for all autoimmune diseases under study, suggesting the requirement of more studies in the field in order to capture such predictive variants that will aid treatment selection.

Influence of the FCGR2A rs1801274 and FCGR3A rs396991 Polymorphisms on Response to Abatacept in Patients with Rheumatoid Arthritis

“…These contradictory results regarding the influence of high- and low-affinity alleles in the FCGR2A rs1801274 and FCGR3A rs396991 SNPs could be determined by the different mechanisms of action of each of the BTs indicated for treatment of RA [ 4 ]. In addition, the differential expression of FCGR2A and FCGR3A in immune system cells could also influence the contradictory response results obtained between the two receptors [ 15 ]. A previous study demonstrated that ABA showed low affinity for the FCGR2 and FCGR3 receptors, and therefore its action through complement-dependent cytotoxicity and ADCC pathways is more limited than may be the case with other BTs that do act through these immunological pathways [ 9 , 59 ].…”

“…Several subtypes of FCGRs have been described, the most extensively studied being FCGR2A and FCGR3A [ 13 , 14 ]. The protein FCGR2A is expressed on monocytes, macrophages, dendritic cells, neutrophils, and platelets, inducing immune reactions such as phagocytosis of opsonized IgGs, ADCC, reactive oxygen species production, and cytokine production [ 15 ]. Similarly, FCGR3A is expressed on monocytes, macrophages, neutrophils, and NK cells, promoting phagocytosis and ADCC mechanisms [ 15 ].…”

“…The protein FCGR2A is expressed on monocytes, macrophages, dendritic cells, neutrophils, and platelets, inducing immune reactions such as phagocytosis of opsonized IgGs, ADCC, reactive oxygen species production, and cytokine production [ 15 ]. Similarly, FCGR3A is expressed on monocytes, macrophages, neutrophils, and NK cells, promoting phagocytosis and ADCC mechanisms [ 15 ]. The affinity of FCGR2A and FCGR3A for the Fc region of IgG of ABA could vary due to structural changes in extracellular domain of the receptors, which could interfere with the therapeutic response to ABA [ 13 , 14 ].…”

“…Similarly, these SNPs are related to the development of autoimmune diseases [ 26 ]. Low-affinity receptors could present less binding and clearance of autoimmune complexes, increasing tissue damage in patients carrying low-affinity variants and producing less response to treatment [ 15 ]. Another recent study, performed by Jiménez Morales et al, identified the high-affinity genotype FCGR2A rs1801274-TT and allele FCGR3A rs396991-G as predictors of greater therapeutic response to rituximab (RTX) and the low-affinity genotype FCGR3A rs396991-TT as a predictor of good response to tocilizumab (TCZ) [ 9 ].…”

Impact of TRAF3IP2, IL10 and HCP5 Genetic Polymorphisms in the Response to TNF-i Treatment in Patients with Psoriatic Arthritis

“…It is known that the variability in treatment response could be affected by multiple factors, including the genetic interindividual variability. Indeed, several studies have investigated the effect of single-nucleotide polymorphisms (SNPs) on response to TNF-i [ 10 , 11 ]. These studies have shown associations between genetic variants and treatment response, suggesting a role of genetic variability in the prediction of the efficacy to this treatment [ 12 ].…”