Association of P2X7R Functional Expression and Gene Polymorphisms with Systemic Lupus Erythematosus

Abstract

Objective: To investigate P2X purinoceptor 7 (P2X7R) expression changes on peripheral blood mononuclear cell (PBMC) surfaces of systemic lupus erythematosus (SLE) patients as well as their association with serum cytokine levels and patients' clinical features. In addition, the effects of different P2X7R single nucleotide polymorphisms (SNPs) on P2X7R expression and cytokine production were investigated.Method: Twenty-nine new-onset SLE patients and twenty-eight healthy controls were enrolled, while P2X7R expression levels of lymphocytes, CD4 + cells and CD19 + cells were analyzed by flow cytometry. Serum IL-1β, IL-6 and TNF-α levels were analyzed by ELISA and three P2X7R SNPs (1068G>A, 1096C>G and 1513A>C) were PCR genotyped in 14 SLE patients and 14 healthy controls.Results: P2X7R surface expression levels of lymphocytes, CD4+ and CD19 + cells from new-onset SLE patients were significantly higher than that of controls and significantly elevated on lymphocytes from patients with concurrent arthritis or leukopenia as well as on CD19 + cells of NP-SLE patients. Moreover, P2X7R expression levels on lymphocytes and CD19 + cells of SLE patients were positively correlated with serum TNF-α/IL-6 and TNF-α level, respectively. SLE patients with the P2X7R 1068GG genotype had significantly higher expression level ratios of TNF-α, IL-6 and IL-1β to P2X7R on lymphocytes compared to patients harboring the 1068GA genotype. Conclusion: P2X7R, as an important cell surface regulator of several key cytokines, is involved in the pathogenesis of SLE and also associated with organ injuries like arthritis, leukopenia and neuropsychiatric damage. P2X7R 1068GG maybe a SLE susceptibility genotype since it enhances cytokine secretion in SLE patients.