TNFα rs1800629 Polymorphism and Response to Anti-TNFα Treatment in Behçet Syndrome: Data from an Italian Cohort Study

Abstract

Tumor Necrosis Factor-alpha (TNFα) rs1800629 (-308G>A) is a single nucleotide polymorphism (SNP) related to variable responses to anti-TNFα therapy. This therapy is efficient in severe and refractory manifestation of Behçet syndrome (BS), an auto-inflammatory systemic vasculitis. We investigated (1) the association between rs1800629 genotypes and responses to therapy and (2) the correlation between SNP and clinical patterns in a cohort of 74 BS Italian patients receiving anti-TNFα therapy with a follow-up of at least 12 months. The rs1800629 was genotyped through amplification, direct sequencing and bioinformatics analyses. The rs1800629 GG and GA genotypes were assessed as predictors of outcomes dividing the patients between therapy responders and non-responders. The rs1800629 GG and GA genotypes were found, respectively, in 59/74 (79.7%) and 15/74 BS patients (21.3%) (p < 0.05). We identified 16/74 (21.9%) non-responder patients, of which 9/16 (56.3%) showed the GG genotype and 7/16 (43.7%) the GA genotype. A total of 50/58 (86.2%) responder patients showed the GG genotype, and 8/58 (13.8%) the GA genotype (p < 0.05). The percentage of non-responder females (68.8%) was significantly higher than non-responder males (31.2%) (p < 0.05). No correlation between SNP and clinical patterns was observed. To successfully include rs1800629 as a predictive biomarker of TNFα inhibitor response, genome-wide association studies in larger, well-characterised cohorts are required.

A case study: ADEM-like lesions as a first clinical event in highly active multiple sclerosis

“…19 in the 105 days following vaccination(Scola et al, 2023), but reports differ whether it can be associated with disease severity(Gupta et al, 2022;Pecoraro et al, 2023). The rs1800629 variant has also been implicated in higher risk for B-cell leukemia(Abdalhabib et al, 2022), lower response to corticosteroids in myasthenia gravis(Li et al, 2023), ine cacy of anti-TNF therapy(Padula et al, 2023), ischemic stroke susceptibility(Kamdee et al, 2021) and lower white matter integrity in schizophrenia(Kang et al, 2022). Variants of interest found in a neuroin ammation SNP panel.IgG binding capacity of FCGR2A(Omar et al, 2012), which is translated into differences in cytokine response(Stein et al, 2019).…”