Tumor Necrosis Factor Alpha -308G/A Gene Polymorphisms Combined with Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio Predicts the Efficacy and Safety of Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis, Rheumatoid Arthritis, and Psoriasis Arthritis

Ziran Wang; Lingjun Kong; Han Zhang; Fengchun Sun; Zijian Guo; Rui Zhang; Yaling Dou

doi:10.3389/fphar.2021.811719

Tumor Necrosis Factor Alpha -308G/A Gene Polymorphisms Combined with Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio Predicts the Efficacy and Safety of Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis, Rheumatoid Arthritis, and Psoriasis Arthritis

Front Pharmacol. 2022 Jan 21:12:811719. doi: 10.3389/fphar.2021.811719. eCollection 2021.

Authors

Ziran Wang¹, Lingjun Kong¹, Han Zhang¹, Fengchun Sun², Zijian Guo¹, Rui Zhang¹, Yaling Dou¹

Affiliations

¹ Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
² Department of Clinical Laboratory, Affiliated Hospital of Jining Medical University, Jining, China.

Abstract

Background: TNF-α has been reported to be closely associated with autoimmune inflammatory diseases. This study aims to investigate the role of TNF-α -308(rs1800629) G/A gene polymorphisms as well as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the efficacy and safety of TNF inhibitors (TNFi) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriasis arthritis (PsA). Methods: A total of 515 subjects (181 AS, 144 RA, 48 PsA, 10 hyperbilirubinemia, 10 hyperlipidemia and 122 healthy control) were recruited in this study. The accuracy of RT-PCR methods for identifying individual TNF-α -308 genotypes was assessed using sequencing as the gold standard. Baseline NLR and PLR of patients with AS, RA and PsA and healthy controls (HC) were calculated and compared. Meanwhile, differences between responders and non-responders to TNFi treatment as well as between individuals with and without adverse effects (AE) among responders were compared. Results: The RT-PCR method is stable and reliable for TNF-α -308G/A gene polymorphism analysis, independent of sample status. The GG genotype was overwhelmingly represented, with relatively few GA genotype, whilst the AA genotype was not detected in this study. There was no observed association between TNF-α-308G/A polymorphism and susceptibility in AS, RA or PsA patients. Patients with AS, RA, and PsA had a higher NLR, compared to the HC group. Apart from PsA patients, AS and RA patients had a higher PLR, compared to the HC group. NLR was positively correlated with PLR. Furthermore, a lack of response was more frequently observed in AS and RA patients that carrying the GA genotype than the GG genotype. AS and RA patients with AE had higher NLR and PLR, compared with the non-AE group. Conclusion: Our study preliminarily shown that combining TNF-α -308G/A polymorphisms with NLR and PLR can predict the responsiveness and safety of anti-TNF therapy in patients with AS or RA.

Keywords: Ankylosing spondylitis; neutrophil-to-lymphocyte ratio; platelet-to-lymphocyte ratio; psoriasis arthritis; rheumatoid arthritis; tumor necrosis factor alpha.