Serum NF-κB p105 and IL-17 in psoriasis: associations with disease status and severity.
TL;DR
Serum NF-κB p105 and IL-17 levels were significantly higher in patients with psoriasis compared to controls, and IL-17 was strongly associated with PASI, whereas NF-κB p105 remained associated with psoriasis status after adjustment for age and BMI.
Abstract
Background
Psoriasis vulgaris is a chronic immune-mediated inflammatory disease recognized as a systemic disorder with cardiometabolic comorbidities. Although the IL-23/Th17 axis is central to pathogenesis, the clinical relevance of circulating inflammatory mediators, particularly nuclear factor kappa B (NF-κB) related proteins, remains incompletely defined.
Objectives
This study aimed to evaluate serum NF-κB p105 and interleukin-17 (IL-17) levels in patients with psoriasis vulgaris, assess their association with disease severity, and explore their discrimination between patients with psoriasis and healthy controls, while accounting for age and BMI.
Methods
In this case-control study, 41 psoriasis vulgaris patients and 47 age- and sex-matched healthy controls were enrolled. Disease severity was assessed using the Psoriasis Area and Severity Index (PASI), and patients were categorized into mild, moderate, or severe disease according to the clinical severity classification by the dermatologist. Serum NF-κB p105 and IL-17 concentrations were measured and compared between groups. Correlations with PASI and body mass index (BMI) were analyzed using Spearman's correlation. Biomarker discrimination within the study cohort was evaluated by receiver operating characteristic (ROC) curve analysis, with bootstrap confidence intervals for the AUC. Because conventional maximum-likelihood logistic regression was unstable in the presence of separation, Firth bias-reduced logistic regression was used to examine factors associated with psoriasis status after adjustment for age and BMI.
Results
Serum NF-κB p105 and IL-17 levels were significantly higher in patients with psoriasis compared to controls (both p < 0.001). IL-17 demonstrated a strong positive correlation with PASI scores (ρ = 0.842, p < 0.001) and increased progressively across mild, moderate, and severe clinical severity categories. NF-κB p105 levels also differed significantly across severity categories but showed only a weak-to-moderate correlation with PASI (ρ = 0.336, p = 0.032), whereas their correlation with IL-17 was moderate (ρ = 0.527, p < 0.001). ROC analysis showed very high apparent discrimination within the present cohort for NF-κB p105 (AUC = 0.994, bootstrap 95% CI: 0.982-1.000), whereas IL-17 showed lower apparent discrimination within the cohort (AUC = 0.868, bootstrap 95% CI: 0.788-0.933). In Firth bias-reduced logistic regression, serum NF-κB p105 remained significantly associated with psoriasis status after adjustment for age and BMI (adjusted OR = 50.60, 95% CI: 2.54-1008.26, p = 0.010), whereas BMI (adjusted OR = 1.67, 95% CI: 0.93-2.99, p = 0.084) and age (adjusted OR = 0.91, 95% CI: 0.80-1.04, p = 0.162) were not statistically significant. However, given the substantial between-group difference in BMI, residual metabolic confounding cannot be excluded despite statistical adjustment.
Conclusions
Serum NF-κB p105 and IL-17 concentrations were higher in patients with psoriasis than in healthy controls. IL-17 was strongly associated with PASI, whereas NF-κB p105 remained associated with psoriasis status after adjustment for age and BMI. However, this adjusted association should not be interpreted as evidence of independence from metabolic confounding, and the wide confidence interval indicates substantial imprecision. Circulating p105 should not be interpreted as a direct measure of NF-κB activation, and the discrimination findings should be considered exploratory and require confirmation in larger, independent cohorts.