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Observational Study
. 2023 Feb 14:14:1043380.
doi: 10.3389/fimmu.2023.1043380. eCollection 2023.

Exploring the association and causal effect between white blood cells and psoriasis using large-scale population data

Guowei Zhou  1   2   3 , Xiangmei Ren  1   2   3 , Zhenwei Tang  1   2   3 , Wang Li  1   2   3 , Wenqiong Chen  1   2   3 , Yi He  1   2   3 , Benliang Wei  1 , Hailun Zhang  4 , Fangyu Ma  5 , Xiang Chen  1   2   3   6 , Guanxiong Zhang  1   2   3 , Minxue Shen  1   7 , Hong Liu  1   2   3   6
Affiliations
Observational Study

Exploring the association and causal effect between white blood cells and psoriasis using large-scale population data

Guowei Zhou et al. Front Immunol. .

Abstract

Introduction: Psoriasis is a chronic inflammatory disease of the skin. A few studies have shown that psoriasis is an immune-mediated disease in which multiple immune cells play crucial roles. However, the association between circulating immune cells and psoriasis remains elusive.

Methods: To explore the role of circulating immune cells in psoriasis, 361,322 individuals from the UK Biobank (UKB) and 3,971 patients with psoriasis from China were included to investigate the association between white blood cells and psoriasis via an observational study. Genome-wide association studies (GWAS) and Mendelian randomization (MR) were used to evaluate the causal relationship between circulating leukocytes and psoriasis.

Results: The risk of psoriasis increased with high levels of monocytes, neutrophils, and eosinophils (relative risks and 95% confidence intervals, respectively: 1.430 (1.291-1.584) for monocytes, 1.527 (1.379-1.692) for neutrophils, and 1.417 (1.294-1.551) for eosinophils). Upon further MR analysis, eosinophils showed a definite causal relationship with psoriasis (odds ratio of inverse-variance weighted: 1.386, 95% confidence intervals: 1.092-1.759) and a positive correlation with the psoriasis area and severity index (PASI) score (P = 6.6 × 10-5). The roles of the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) in psoriasis were also assessed. More than 20,000 genetic variations associated with NLR, PLR, and LMR were discovered in a GWAS analysis using the UKB data. Following adjustment for covariates in the observational study, NLR and PLR were shown to be risk factors for psoriasis, whereas LMR was a protective factor. MR results indicated that there was no causal relationship between these three indicators and psoriasis; however, NLR, PLR, and LMR correlated with the PASI score (NLR: rho = 0.244, P = 2.1 × 10-21; PLR: rho = 0.113, P = 1.4 × 10-5; LMR: rho = -0.242, P = 3.5×10-21).

Discussion: Our findings revealed an important association between circulating leukocytes and psoriasis, which is instructive for the clinical practice of psoriasis treatment.

Keywords: Mendelian randomization; lymphocyte-monocyte ratio; neutrophil-lymphocyte ratio; platelet-lymphocyte ratio; psoriasis; white blood cells.

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Conflict of interest statement

Author HZ was employed by Beijing GAP Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the study about white blood cells and psoriasis.
Figure 2
Figure 2
Association between circulating white blood cells and psoriasis in UKB. (A) RRs of psoriasis from categories of white blood cells (the first category was viewed as a reference). (B) Association between white blood cells and psoriasis in univariate Cox regression. (C) Association between white blood cells and psoriasis after adjusting for covariates in multivariate Cox regression (sex, age, BMI, smoking status, and alcohol drinking status).
Figure 3
Figure 3
Causal relationship between white blood cells and psoriasis in two-sample MR analysis. (A) Heatmap of two-sample MR results about white blood cells and psoriasis (* represented P < 0.05). (B) Scatter plot of MR analysis related to eosinophil count and psoriasis. (C) Scatter plot of MR analysis related to white blood cell sum count and psoriasis. (D) Result of multivariable MR on different white blood cells and psoriasis. (E) Correlation between eosinophil count and severity of psoriasis (Spearman’s correlation).
Figure 4
Figure 4
Relationship between white blood cell ratios (NLR, PLR, and LMR) and psoriasis. (A) Result of observational study about white blood cell ratios (NLR, PLR, and LMR) and psoriasis in UKB (Covariates included sex, age, BMI, smoking status, and alcohol drinking status and three ratios in multivariate Cox regression). (B) Scatter plot of MR analysis related to NLR and psoriasis. (C) Scatter plot of MR analysis related to PLR and psoriasis. (D) Scatter plot of MR analysis related to LMR and psoriasis. (E) Correlation between the three ratios and severity of psoriasis (Spearman’s correlation).
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