Abstract: 【Abstract】 Objective To investigate the efficacy and safety of infliximab in the treatment of severe plaque psoriasis and its effect on the expression of programmed cell death-1 （PD-1） and programmed cell death ligand-1 （PD-L1） in psoriatic lesions. Methods A total of 17 patients with severe plaque psoriasis were enrolled from Shanghai Skin Disease Hospital from February 2019 to April 2019, and were treated with intravenous drips of infliximab at a dose of 5 mg/kg at weeks 0, 2, 6, 14, 22, 30, 38 and 46. Efficacy was evaluated by using the psoriasis area and severity index （PASI） score at weeks 2, 6, 10, 14, 22, 30, 38, 46 and 52, and adverse events were recorded during the trial. Real-time PCR was performed to determine the expression of PD-1 and PD-L1 in skin tissues of 8 volunteer controls, as well as in skin lesions of 14 patients with plaque psoriasis before treatment and 5 patients with plaque psoriasis after 10-week treatment, and immunofluorescence assay to measure the expression of PD-1 and PD-L1 in skin tissues of 5 volunteers and 5 patients with psoriasis. The independent sample t-test was used to compare the expression of PD-1 and PD-L1 in skin tissues between the patients with plaque psoriasis and controls, and paired t-test to compare the expression of PD-1 and PD-L1 in the skin lesions of patients before and after infliximab treatment. Results After 2, 6, 10, 14, 22, 30, 38, 46 and 52 weeks of infliximab treatment, the proportion of patients with plaque psoriasis achieving PASI75 was 1/17, 6/16, 9/16, 10/16, 15/15, 14/15, 13/14, 11/13 and 10/11, respectively. Antinuclear antibody staining turned positive in 12 patients, which was the most common adverse reaction, and 1 patient experienced an infusion reaction, which was the most severe adverse reaction. Before the treatment, the expression of PD-1 and PD-L1 （1.111 ± 0.391, 0.902 ± 0.169, respectively） was significantly higher in the skin lesions of patients with psoriasis than in the skin tissues of controls （0.620 ± 0.225, t = 3.116, P = 0.007; 0.474 ± 0.360, t = 3.208, P = 0.006, respectively）; after infliximab treatment, the expression of PD-1 and PD-L1 （0.570 ± 0.230, 0.150 ± 0.050, respectively） in the improved skin lesions was significantly lower than that in the corresponding lesions before the treatment （1.238 ± 0.414, t = 3.107, P = 0.036; 0.966 ± 0.184, t = 8.423, P = 0.001, respectively）. Conclusions Infliximab is effective and safe for the treatment of plaque psoriasis, but monitoring is necessary during treatment. The expression of PD-1 and PD-L1 is aberrantly upregulated in plaque psoriasis lesions, and decreased after infliximab treatment, suggesting that PD-1/PD-L1 may be involved in inflammation regulation in psoriasis.

Key words: Psoriasis, Tumor necrosis factor-alpha, Biological agents, Programmed cell death 1 receptor, Antigens, CD274, Treatment outcome, Co-inhibitory receptors, Infliximab