PD-1 gene rs2227981 (PD-1.5) polymorphism analysis in patients with systemic sclerosis

Recently, some cases of scleroderma-like reactions have been reported in oncological patients treated with immune checkpoint inhibitors (ICIs) and in particular PD-1 inhibitors (nivolumab and pembrolizumab). PD-1 is a checkpoint protein found in T lymphocytes. Its binding with PD-ligand 1 (PD-L1) prevents autoimmunity and promotes self-tolerance by downmodulating T-cell activity. The literature suggests that deficiency in co-inhibitory receptor including PD-1 can be associated with the development of autoimmune diseases. The gene coding for PD-1 (PDCD1) presents several polymorphisms and PD-1 rs2227981 (PD-1.5) polymorphism is one of the most studied as it has been reported in association with other human autoimmune diseases. This study aimed to analyze PD-1 C>T rs2227981 single nuclear polymorphism and its possible association with the development of systemic sclerosis. The study comprehended 144 subjects (69 cases diagnosed with scleroderma with the ACR-EULAR criteria of 2013 and 75 healthy controls). No significant difference emerged between systemic sclerosis patients and healthy controls as regard genotype (p = 0.2775) and allele analysis (p = 0.1568). Our results do not suggest an association between PD-1 C/T rs2227981 polymorphism and a predisposition to develop systemic sclerosis. Despite this, our study does not exclude the association with other PD-1 polymorphisms with systemic sclerosis. Moreover, this study reported a single-center experience, thus the generalization of the findings is limited to similar settings.