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Longitudinal variation of serum PCSK9 in ulcerative colitis: association with disease activity, T helper 1/2/17 cells, and clinical response of tumor necrosis factor inhibitor

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Abstract

Aims

Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates CD4+ T cell differentiation and inflammatory response, the latter ones mediate ulcerative colitis (UC) initiation. This study intended to explore the correlation of serum PCSK9 with disease activity, T helper (h)1/Th2/Th17 cells, and clinical response of tumor necrosis factor inhibitor (TNFi) in UC patients.

Methods

In 65 UC patients underwent TNFi treatment, serum PCSK9 was evaluated at baseline (W0), week (W)2, W6, and W12 by enzyme-linked immunosorbent assays; meanwhile, Th1/Th2/Th17 cells were determined at W0 by flow cytometry. Besides, serum PCSK9 was detected in 65 healthy controls (HCs).

Results

Serum PCSK9 was increased in UC patients compared to HCs (P<0.001), which also positively correlated with C-reactive protein (P=0.009), total Mayo score (P=0.018), Mayo-defined disease activity (P=0.020), Th1 (P=0.033), and Th17 (P=0.003) cells, but not Th2 cells (P=0.086) in UC patients. Interestingly, serum PCSK9 was steadily declined from W0 to W12 (P<0.001). W2-W0, W6-W0, and W12-W0 serum PCSK9 change (PCSK9 at W2, W6, or W12 minus PCSK9 at W0, respectively) was gradually becoming greater during TNFi treatment (P<0.001). Furthermore, forty-five (69.2%) patients achieved clinical response at W12, whose serum PCSK9 at W6 (P=0.041) and W12 (P=0.001) was lower, and W6-W0 (P=0.043), W12-W0 (P=0.019) serum PCSK9 change was more obvious compared to patients without clinical response at W12.

Conclusions

Serum PCSK9 is positively related to disease activity, Th1, and Th17 cells in UC patients; further, its decline correlates with TNFi response achievement in these patients.

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Data availability

The data utilized in this study are included in the article.

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Authors and Affiliations

  1. Department of Anorectal Surgery, Harbin Traditional Chinese Medicine Hospital, No.2 Xinglin Street, Harbin, 150000, China

    Jialin Deng, Yongqian Jiang, Liyan Luan, Siyang Fu, Mengsi Huang, Zixun Dai, Yunzheng Liao & Yuxiang Fu

  2. Department of Pharmacy, Harbin Traditional Chinese Medicine Hospital, Harbin, 150000, China

    Shupeng Guo

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Deng, J., Jiang, Y., Luan, L. et al. Longitudinal variation of serum PCSK9 in ulcerative colitis: association with disease activity, T helper 1/2/17 cells, and clinical response of tumor necrosis factor inhibitor. Ir J Med Sci 193, 165–172 (2024). https://doi.org/10.1007/s11845-023-03440-4

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