Background: Tumor necrosis factor-alpha (TNF-α), IL-12/23, IL-17A, and IL-17F are key proinflammatory cytokines involved in the pathogenesis of psoriasis. Biologic therapies targeting these interleukins have demonstrated clinical efficacy. However, the exact relationship between their serum levels and clinical response remains unclear. The aims of this study are to assess changes in cytokine levels (TNF-α, IL-12/23, IL-17A, IL-17F) after 12 weeks of biologic treatment in psoriasis to test if there is any correlation between their serum level and PASI (Psoriasis Area Severity Index) and DLQI (Dermatology Life Quality Index) scores before or after treatment and to check the influence of clinical and lifestyle factors on these levels. Methods: In this prospective study, 36 patients with moderate-to-severe plaque psoriasis receiving anti-TNF-α, anti-IL-17, or anti-IL-23 therapy were assessed at baseline and after 12 weeks. The serum levels of these cytokines were measured using the ELISA technique. Clinical response was evaluated using PASI and DLQI scores. Spearman correlation analysis was used to assess the relationship between interleukins’ serum levels and these scores. Results: A significant decrease in TNF-α levels and DLQI and PASI scores was observed after 12 weeks across all treatments. A moderate positive correlation (r = 0.391, p = 0.018) was found between serum TNF-α levels and PASI scores at week 12. Conclusions: The serum levels of TNF-α are significantly correlated with PASI scores following 12 weeks of biologic therapy, supporting their potential role as a biomarker for monitoring treatment efficacy in psoriasis.

Psoriasis is a chronic, inflammatory disease with a complex pathogenesis that is not yet fully understood. Although it is a multifactorial disease, the genetic factor has a major role in the pathogenesis of psoriasis. Genome wide association studies have identified over 50 genetic loci associated with psoriasis risk. Beside TNF-α or IL-23, the IL-17 family is a newer group that has proven implications in the pathogenesis of psoriasis. The most important members of the family, with pro-inflammatory qualities, are IL-17A and IL-17F. These interleukins are produced by a varied number of cells, but by far the most important are Th17 cells. Of the patients 20-30% present moderate-to-severe psoriasis, therefore, systemic medication (phototherapy, methotrexate, cyclosporine, acitretin or biologic agents) is mandatory. The necessity of an individualized treatment plan, for each patient, is imperative in order to establish the best strategy for non-responders to classical treatment or to other biologic treatments. The discovery of Th17 pathway improved the treatment and prognosis of psoriasis. Anti-psoriatic agents against IL-17 or its receptors are a novel group of biologic agents; these include ixekizumab, secukinumab and brodalumab. Polymorphisms of IL-17 family have been correlated with the severity and response to treatment in psoriasis, and also with the risk of inflammatory, infectious, autoimmune or neoplastic pathologies. The significant difference in the presence or absence of susceptibility loci in different population is due to genetic background and environmental factors that have a major impact on disease predisposition. In this study, we reviewed the importance and influence of the IL-17 polymorphisms as predictors of response to treatment and severity of the disease.

Psoriasis is a systemic inflammatory disease that associates with multiple comorbidities. It involves complex interactions between environmental factors and polygenic predisposition. The IL-17 family is one of the main actors in the pathogenesis of psoriasis. Secondary nonresponse is common, especially during the long-term use of TNF-α inhibitors, but it is not uncommon even for newer biologics, such as IL-17 inhibitors. Identification of clinically useful biomarkers of treatment efficacy and safety would enable optimal treatment selection, improve patient quality of life and outcome, and reduce healthcare costs. To our knowledge, this is the first study to evaluate the relationship between genetic polymorphism of IL-17F (rs763780) and IL-17RA (rs4819554) and response to biological treatment and other clinical data in bio-naive and secondary non-responders psoriasis patients in Romania and Southeastern Europe. We performed a prospective, longitudinal, analytical cohort study of 81 patients diagnosed with moderate-to-severe chronic plaque psoriasis who received biological treatments for the first time. Of the 79 patients treated with TNF-α inhibitors, 44 experienced secondary nonresponse. All patients were genotyped for the two SNPs in IL-17F and IL-17RA genes. The rs763780 polymorphism in the IL-17F gene could be an attractive candidate biomarker for predicting which patients will respond to anti-TNF-α therapies. Another emergent association of rs4819554 in IL-17RA with the risk of nail psoriasis and a higher BMI in moderate-to-severe plaque psoriasis patients is described.

Background: Psoriasis is a chronic immune-mediated inflammatory disease with a strong genetic basis, driven in part by the dysregulation of the IL-23/Th17 signaling axis. Variants in the IL23R and IL12B genes have been associated with psoriasis susceptibility; however, data from Eastern European populations remains scarce. Objective: We aimed to evaluate the link between IL23R rs11209026 and IL12B rs3213094 polymorphisms and psoriasis susceptibility in a multi-center, Romanian cohort. Methods: We performed a multi-center case–control study including adult patients with clinically and histopathologically confirmed moderate-to-severe psoriasis undergoing biological therapy and controls without autoimmune or chronic inflammatory diseases. Genotyping was performed using TaqMan SNP assays. Associations were analyzed under a dominant genetic model. Results: A significant association was observed between IL23R rs11209026 polymorphism and psoriasis susceptibility. Carriers of the A allele (AA+GA) showed reduced odds of psoriasis compared with the GG homozygotes, emphasizing the protective effect of this specific variant. No significant association was identified for IL12B rs3213094 polymorphism. Conclusions: Our findings support the protective association of IL23R rs11209026 A allele with psoriasis in a Romanian Eastern European population and emphasize the importance of the IL-23 pathway in disease pathogenesis. Alcohol consumption was independently associated with increased risk of psoriasis. Further studies are justified to explore potential pharmacogenetic implications.

Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease characterized by heterogeneous clinical presentation and variable response to biologic therapy. Genetic variation within the IL-23/Th17 inflammatory pathway may influence treatment outcomes. This study evaluated the association between IL12B rs3213094 and IL23R rs11209026 single-nucleotide polymorphisms (SNPs) and response to biologic therapy in patients with moderate-to-severe psoriasis. Materials and Methods: We conducted a multicenter observational study including 92 Romanian patients with moderate-to-severe psoriasis vulgaris receiving their first biologic therapy (anti-TNF, anti-IL-17, or anti-IL-23 monoclonal antibodies). Clinical response was assessed using the Psoriasis Area and Severity Index (PASI) at baseline and weeks 12, 24, 36, and 48. Early response was defined as achieving PASI75 at week 12. Patient-reported disease impact was assessed using the Dermatology Life Quality Index (DLQI) at the same time points. Genotyping of IL12B rs3213094 and IL23R rs11209026 was performed using TaqMan assays. Longitudinal PASI dynamics were analyzed using repeated-measures ANOVA, while multivariable logistic regression was used to identify independent predictors of PASI75 at week 12. Results: A significant reduction in PASI scores over time was observed (p < 0.001). The IL12B rs3213094 genotype was associated with differences in early response kinetics, with T-allele carriers showing significantly greater PASI improvement at week 12 compared with CC homozygotes (90.0% vs. 65.7%, p = 0.003). This effect was limited to early treatment and attenuated at later time points. In multivariable analysis, the IL12B rs3213094 CT + TT genotype was independently associated with PASI75 achievement at week 12 (OR = 4.285, 95% CI 1.500–12.239, p = 0.007). Treatment with anti-IL-17 agents was also an independent predictor of early response (OR = 3.946, 95% CI 1.416–10.998, p = 0.009). No significant association was observed between IL23R rs11209026 and treatment response. DLQI scores improved significantly over time (p < 0.001), without genotype-dependent differences. Conclusions: IL12B rs3213094 SNP is significantly associated with early biologic treatment response in psoriasis, supporting its potential role as a pharmacogenetic biomarker of treatment responsiveness. These findings may inform the integration of genetic markers into personalized therapeutic strategies, particularly in underrepresented populations such as those from Eastern Europe. Further studies in larger cohorts are warranted to validate these results.