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

Zhou, Guowei; Ren, Xiangmei; Tang, Zhenwei; Li, Wang; Chen, Wenqiong; He, Yi; Wei, Benliang; Zhang, Hailun; Ma, Fangyu; Chen, Xiang; Zhang, Guanxiong; Shen, Minxue; Liu, Hong

doi:10.3389/fimmu.2023.1043380

Cited by 8 publications

(13 citation statements)

References 78 publications

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“…This underscores the necessity for early monitoring of in ammatory markers and proactive in ammation management, a trend gaining traction in the clinical landscape of immune-mediated in ammatory diseases. Current consensus leans towards employing the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in psoriasis assessment, with studies demonstrating their association with the disease, albeit not directly correlating with severity [22][23][24][25]. Notably, biologic therapies have shown e cacy in reducing NLR and PLR levels, highlighting their utility as biomarkers in monitoring disease trajectory and treatment response [35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Association between systemic immune-inflammation index and psoriasis: A cross-sectional study

Bo,

Zhong,

Ren

et al. 2024

Preprint

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Objectives The Systemic Immune-inflammatory Index (SII), an emergent biomarker for inflammation, has recently garnered attention. Psoriasis, characterized by its immune-inflammatory nature, presents an intriguing domain for exploring potential associations with SII. This investigation is poised to unravel the complexities of this relationship. Methods Leveraging data from the National Health and Nutrition Examination Survey (NHANES), spanning five distinct cycles (2003–2004, 2005–2006, 2009–2010, 2011–2012, and 2013–2014), this cross-sectional study meticulously calculated the SII, taking into account lymphocyte, neutrophil, and platelet counts. Questionnaire data from individuals with psoriasis were meticulously analyzed. An array of statistical methodologies was employed to discern the linear and non-linear relationships between SII and psoriasis, including multivariate regression, subgroup analyses, smoothed curve fitting, and threshold effect analyses. Results Encompassing a demographic of 23,825 Americans, this population-based study identified 623 individuals (2.61%) with psoriasis. Following a rigorous adjustment for pivotal covariates such as age, gender, and race, multivariate logistic regression analyses unveiled a significant and positive correlation between SII and psoriasis (OR = 1.14, 95% CI = 1.01–1.29, P = 0.0286), with the interaction test demonstrating robustness in this association. Intriguingly, the relationship between SII and psoriasis was elucidated to be non-linear, as evidenced by a two-stage linear regression model, pinpointing an inflection point at 790.4 (1,000 cells/l). Conclusion The present study establishes an independent association between a self-reported history of psoriasis and SII. Moreover, it delineates SII as an independent risk factor for psoriasis at levels below 790.4 (1,000 cells/l), thereby contributing valuable insights into the immunological landscape of psoriasis.

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Section: Discussionmentioning

confidence: 99%

Association between systemic immune-inflammation index and psoriasis: A cross-sectional study

Bo,

Zhong,

Ren

et al. 2024

Preprint

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“…These findings suggest that MASLD exacerbates skin manifestations and inflammation of psoriatic lesions. Additionally, a Mendelian randomization study suggested that a rise in white blood cell count and neutrophils could be risk factors for the onset of psoriasis ( 49 ). Thus, the increased levels of these cells observed in the MASLD group might indicate an exacerbation of psoriasis when associated with MASLD.…”

Section: Discussionmentioning

confidence: 99%

Metabolic dysfunction associated steatotic liver disease in patients with plaque psoriasis: a case–control study and serological comparison

Lin,

Shi,

et al. 2024

Front. Med.

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BackgroundThe relationship between plaque psoriasis and both MASLD and lean MASLD has not been sufficiently explored in the current literature.MethodThis retrospective and observational study was carried out from January 2021 to January 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University. Patients diagnosed with plaque psoriasis and a control group consisting of individuals undergoing routine physical examinations were enrolled. The incidence of MASLD and lean MASLD among these groups was compared. Additionally, patients with plaque psoriasis were divided into those with MASLD, those with lean MASLD, and a control group with only psoriasis for a serological comparative analysis.ResultsThe incidence of MASLD in the observation group and the control group was 43.67% (69/158) and 22.15% (35/158), respectively (p < 0.01). Furthermore, the incidence of lean MASLD within the observation group and the control group was 10.76% (17/158) and 4.43% (7/158), respectively (p < 0.01). After controlling for potential confounding variables, plaque psoriasis was identified as an independent risk factor for MASLD with an odds ratio of 1.88 (95% cl: 1.10–3.21). In terms of serological comparison, compared to the simple psoriasis group, we observed a significant elevation in the tumor marker CYFRA21-1 levels in both groups compared to the control group with simple psoriasis (p < 0.01). Moreover, the MASLD group exhibited elevated levels of inflammatory markers and psoriasis score, whereas these effects were mitigated in the lean MASLD group.ConclusionThe prevalence of MASLD and lean MASLD is higher among patients with psoriasis. Those suffering from psoriasis along with MASLD show increased psoriasis scores and inflammatory markers compared to those without metabolic disorders. MASLD likely worsens psoriasis conditions, indicating the necessity of targeted health education for affected individuals to reduce the risk of MASLD, this education should include guidelines on exercise and diet. In serological assessments, elevated levels of cytokeratin 19 fragment (CYFRA21-1) were noted in both MASLD and lean MASLD groups, implying a potential synergistic role between psoriasis and MASLD.

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“…Here, we propose a new intermediate trait category for use in proxying drug targets in IMD: immune cell abundance. There is substantial animal model, observational and MR evidence[21–26] implicating immune cell dysregulation in the pathogenesis of immune-mediated disorders, ranging from roles of T H 2 cells, eosinophils, and neutrophils in allergic conditions like asthma[27,28] and eczema[29,30] to expansion of certain T helper lymphocyte and B lymphocyte lineages in autoimmune diseases such as systemic lupus erythematosus (SLE)[31], multiple sclerosis[32] and rheumatoid arthritis[5]. Furthermore, approved drug targets for IMD are usually classed as immunosuppressants or immunomodulators, which alter the balance of immune blood cells in their course of on-target action.…”

Section: Introductionmentioning

confidence: 99%

Integrative Mendelian Randomization approaches for therapeutic target prioritisation in immune-mediated diseases

Sobczyk,

Gaunt

2024

Preprint

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Background: Immune-mediated diseases (IMD) encompass a wide range of autoimmune and inflammatory disorders with aetiology related to immune system dysfunction, signifying a disease area with great potential for drug repurposing. In this study, we employed the genetically informed Mendelian Randomization (MR) method with two distinct exposure types: immune blood cell abundance and protein quantitative trait loci (pQTL) to validate and repurpose 834 drug targets which have been investigated for IMD treatment. Methods: Utilizing two-sample MR, we first established causal relationships between major peripheral immune cell types and 14 IMD. Robust associations, particularly with eosinophils, were confirmed across diseases such as asthma, eczema, sinusitis, and rheumatoid arthritis, revealing 59 high-confidence relationships. Intragenic variants associated with causal immune cell types were then extracted to create instruments for 371 existing IMD drug targets ("intermediate trait" MR). In parallel, we leveraged four large blood plasma protein QTL datasets to obtain complementary instruments for 361 targets ("pQTL" MR). Results: In the intermediate trait MR analysis, we identified 811 gene-IMD associations (p-value <0.05), 169 of which were supported by strong colocalisation evidence (PPH4 > 0.8). In the pQTL MR analysis, we similarly found 841 protein-IMD associations (p-value <0.05), 83 of which were confirmed with colocalization. Comparison with a list of approved drugs indicated low sensitivities across disease outcomes for both exposure types (intermediate trait MR: 0.49 +/- 0.23 SD, pQTL MR: 0.28 +/- 0.12 SD). Conclusions: Drug targets identified in the pQTL and intermediate trait MR analyses show limited overlap (13%), presenting a comprehensive source of drug repurposing opportunities when the two approaches are combined.

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

Cited by 8 publications

References 78 publications

Association between systemic immune-inflammation index and psoriasis: A cross-sectional study

Association between systemic immune-inflammation index and psoriasis: A cross-sectional study

Metabolic dysfunction associated steatotic liver disease in patients with plaque psoriasis: a case–control study and serological comparison

Integrative Mendelian Randomization approaches for therapeutic target prioritisation in immune-mediated diseases

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