Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.

Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD‐1, TIGIT, and TIM‐3 in Lymphocytes From Patients With Systemic Sclerosis

“…However, the co-IR expression patterns on various lymphocyte subsets show considerable disease-dependent variation. For example, PD-1 is increased in CD4 + and CD8 + T and NK cells from lupus patients (36,37), and in CD3 + T cells from psoriatic arthritis patients (38), while in SSc it is only significantly enhanced in Tregs and γδ T cells (Fig. 1C).…”

Percentages of PD-1+CD4+T cells and PD-L1+DCs are increased and sPD-1 level is elevated in patients with immune thrombocytopenia

“…It is reported that PD-1/PD-L1 signaling pathway plays negative regulation roles in autoimmune diseases such as glomerular nephritis, autoimmune encephalomyelitis, psoriatic arthritis, and Sjogren's syndrome. [11][12][13][14][15] In addition, activation of PD-1/PD-L1 signaling pathway in rheumatoid arthritis patients effectively inhibits the proliferation of Th1 and Th17 cells and the secretion of IFN-g and IL-17 cytokines. 16 sPD-1 is the soluble form of PD-1 that is obtained by phosphoric acid hydrolysis of membrane type PD-1.…”

PDCD1single nucleotide genes polymorphisms confer susceptibility to juvenile-onset systemic lupus erythematosus

“…Previous studies have indicated the frequentness of PD1.1 G/A (rs36084323) in the Chinese Han population (49%), but its' scarcity in Europeans (1%), which may be associated with the Chinese Han population more susceptibility to SLE [4]. Nonetheless, Jiao et al observed no correlation between SNP PD1.1 G/A (rs36084323) and enhanced expression of PD1 in PBMCs from SLE patients [7]. As the PD1.1 is located within PD1 promoter region and the SNP at this location could exert no function, further study is required to shed the light on the precise role of this SNP in the pathogenesis of JSLE.…”

“…In addition, the development of lupus-like syndrome has been identified in PD-1 deficient mice [4]. Several association studies have been conducted to assess the potential correlations of various single nucleotide polymorphisms (SNPs) in PDCD1 gene, known to affect the level of PD-1 expression, with adult-onset SLE proneness so far [4][5][6][7][8][9]. However, there is a paucity of data regarding the associations of PDCD1 SNPs with individuals' susceptibility to JSLE.…”