Search Results (885)

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Blood-based biomarkers allow monitoring of an individual’s health status and provide insights into metabolic and inflammatory processes in conditions like obesity, cardiovascular, and liver diseases. However, selecting suitable biomarkers and optimizing analytical assays presents challenges, is time-consuming and laborious. Moreover, knowledge of potential sex differences remains incomplete as research is often carried out in men. This study aims at enabling researchers to make informed choices on the type of biomarkers, analytical assays, and dilutions being used. More specifically, we analyzed plasma concentrations of >90 biomarkers using commonly available ELISA or electrochemiluminescence-based multiplex methods, comparing normal weight (BMI < 25; n = 40) with obese (BMI > 30; n = 40) adult blood donors of comparable age. To help choose optimal biomarker sets, we grouped frequently employed biomarkers into biological categories (e.g., adipokines, acute-phase proteins, complement factors, cytokines, myokines, iron metabolism, vascular inflammation), first comparing normal-weight with obese persons, and thereafter exploratively comparing women and men within each BMI group. Many biomarkers linked to chronic inflammation and dysmetabolism were elevated in persons with obesity, including several adipokines, interleukins, chemokines, acute-phase proteins, complement factors, and oxidized LDL. Further exploration suggests sex disparities in biomarker levels within both normal-weight and obese groups. This comprehensive dataset of biomarkers across diverse biological domains constitutes a reference resource that may provide valuable guidance for researchers in selecting appropriate biomarkers and analytical assays for own studies. Moreover, the dataset highlights the importance of taking possible sex differences into account. Full article

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

Reproductive efficiency is largely impacted during heifer development, which generally requires nutrient supplementation for proper maturation. Nutritional status can also influence inflammation within the reproductive tract. Therefore, we hypothesized that cytokine concentrations in uterine luminal fluid (ULF) will be impacted by protein supplementation following exposure to semen via artificial insemination (AI). Commercial heifers (n = 60) were utilized to determine the effects of protein supplementation and AI on cytokine concentrations in ULF. Heifers were randomly assigned to one of three crude protein (CP) treatments (11%, 15%, and 19% overall CP) via supplementation: (1) CON (10% CP), (2) P20 (20% CP), and (3) P40 (40% CP). All heifers underwent estrus synchronization and ULF was collected 14 d after insemination. Cytokine profiles were constructed in MetaboAnalyst 5.0, and R Studio was used for individual cytokine analyses. Control heifers had increased (p = 0.05) MIP-1β concentrations (148.7 ± 123.9 pg) over P20 heifers (42.3 ± 123.9 pg), and P40 heifers (75.5 ± 123.9 pg) had intermediate concentrations. Semen exposure (1877 ± 550 pg) showed a trend (p = 0.06) to increase concentrations of IP-10 compared with heifers who were not inseminated (1556 ± 550 pg). In conclusion, although protein supplementation and semen exposure had minimal effects on overall cytokine profiles, MIP-1β, IP-10, and MIP-1α were identified as potential key regulators of uterine inflammation during early gestation. Full article

Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised with pulmonary TB. We analysed 80 adults with microbiologically confirmed pulmonary TB and 40 respiratory symptom controls; four TB patients (5%) died during hospitalisation, all within 10 days of admission. Methods: A retrospective analytical case–control study was conducted at the Constanța regional TB referral centre (October 2020—October 2023). Patients with smear- or culture-confirmed TB were frequency-matched by sex, 10-year age band, and BMI class to culture-negative respiratory controls at a 2:1 ratio. The patients’ serum interferon-γ (IFN-γ), interleukin-1α (IL-1α), interleukin-1β (IL-1β), and tumour-necrosis-factor-α (TNF-α) were quantified within 24 h of admission; the neutrophil/lymphocyte ratio (NLR) was extracted from full blood counts. Independent predictors of in-hospital mortality were identified by multivariable logistic regression; factors associated with the length of stay (LOS) were modelled with quasi-Poisson regression. Results: The median TNF-α (24.1 pg mL⁻¹ vs. 16.2 pg mL⁻¹; p = 0.009) and IL-1β (5.34 pg mL⁻¹ vs. 3.67 pg mL⁻¹; p = 0.008) were significantly higher in the TB cases than in controls. TNF-α was strongly correlated with IL-1β (ρ = 0.80; p < 0.001), while NLR showed weak concordance with multiplex cytokine patterns. Among the patients with TB, four early deaths (5%) exhibited a tripling of TNF-α (71.4 pg mL⁻¹) and a doubling of NLR (7.8) compared with the survivors. Each 10 pg mL⁻¹ rise in TNF-α independently increased the odds of in-hospital death by 1.8-fold (95% CI 1.1–3.0; p = 0.02). The LOS (median 29 days) was unrelated to the smoking, alcohol, or comorbidity load, but varied across BMI strata: underweight, 27 days; normal weight, 30 days; overweight, 23 days (Kruskal–Wallis p = 0.03). In a multivariable analysis, under-nutrition (BMI < 18.5 kg m⁻²) prolonged the LOS by 19% (IRR 1.19; 95% CI 1.05–1.34; p = 0.004) independently of the disease severity. Conclusions: A hyper-TNF-α/IL-1β systemic signature correlates with early mortality in Romanian pulmonary TB, while under-nutrition is the dominant modifiable determinant of prolonged hospitalisation. Admission algorithms that pair rapid TNF-α testing with systematic nutritional assessment could enable targeted host-directed therapy trials and optimise bed utilisation in high-burden settings. Full article

Uterine leiomyoma (uterine fibroids, UF) are benign myometrium tumors that affect up to 70% of the female population and may lead to severe clinical symptoms. Despite the high prevalence, pathogenesis of UF is not understood and involves cytokines, steroid hormones, and growth factors. Additionally, an increased deposition and remodelling of the extracellular matrix is characteristic for UF. Vitamin D seems to play a new role in UF. Interestingly, hypovitaminosis D correlates with a higher prevalence of myomas and the severity of the myomas. Administration of vitamin D in women with insufficiency (serum level <30 ng/mL) restored the vitamin D status and reduced the mild symptoms of myomas. In addition, inflammatory processes may play a role. In the past years, it has become clear that cessation of inflammation is an active process driven by a class of lipid mediator molecules called specialized pro-resolving mediators (SPM). Inadequate resolution of inflammation is related to several chronic inflammatory diseases and several studies have proven the crucial role of SPMs in improving these diseases. In this review, we will give an overview on processes involved in UF growth and will give an overview on the modern view regarding the concept of inflammation and the role of SPMs in resolution of inflammation, especially in chronic inflammatory diseases. Full article

Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict patient outcomes. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied extensively in cardiovascular disease, but its investigation in PAD remains limited. This study aimed to use explainable statistical and machine learning methods to assess the prognostic value of GDF15 for limb outcomes in patients with PAD. Methods: This prognostic investigation was carried out using a prospectively enrolled cohort comprising 454 patients diagnosed with PAD. At baseline, plasma GDF15 levels were measured using a validated multiplex immunoassay. Participants were monitored over a two-year period to assess the occurrence of major adverse limb events (MALE), a composite outcome encompassing major lower extremity amputation, need for open/endovascular revascularization, or acute limb ischemia. An Extreme Gradient Boosting (XGBoost) model was trained to predict 2-year MALE using 10-fold cross-validation, incorporating GDF15 levels along with baseline variables. Model performance was primarily evaluated using the area under the receiver operating characteristic curve (AUROC). Secondary model evaluation metrics were accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Prediction histogram plots were generated to assess the ability of the model to discriminate between patients who develop vs. do not develop 2-year MALE. For model interpretability, SHapley Additive exPlanations (SHAP) analysis was performed to evaluate the relative contribution of each predictor to model outputs. Results: The mean age of the cohort was 71 (SD 10) years, with 31% (n = 139) being female. Over the two-year follow-up period, 157 patients (34.6%) experienced MALE. The XGBoost model incorporating plasma GDF15 levels and demographic/clinical features achieved excellent performance for predicting 2-year MALE in PAD patients: AUROC 0.84, accuracy 83.5%, sensitivity 83.6%, specificity 83.7%, PPV 87.3%, and NPV 86.2%. The prediction probability histogram for the XGBoost model demonstrated clear separation for patients who developed vs. did not develop 2-year MALE, indicating strong discrimination ability. SHAP analysis showed that GDF15 was the strongest predictive feature for 2-year MALE, followed by age, smoking status, and other cardiovascular comorbidities, highlighting its clinical relevance. Conclusions: Using explainable statistical and machine learning methods, we demonstrated that plasma GDF15 levels have important prognostic value for 2-year MALE in patients with PAD. By integrating clinical variables with GDF15 levels, our machine learning model can support early identification of PAD patients at elevated risk for adverse limb events, facilitating timely referral to vascular specialists and aiding in decisions regarding the aggressiveness of medical/surgical treatment. This precision medicine approach based on a biomarker-guided prognostication algorithm offers a promising strategy for improving limb outcomes in individuals with PAD. Full article

The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients. Full article

Endothelial dysfunction contributes to the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD). Pemafibrate has been shown to ameliorate MASLD in basic and clinical studies, but it is unclear whether it is also effective in the status of endothelial dysfunction. An MASLD animal model was induced in male wild-type (WT) and endothelial nitric oxide synthase (eNOS)-deficient (eNOSKO) mice by feeding them a high-fat/cholesterol/cholate diet, and they were administered either a vehicle or pemafibrate at 0.17 mg/kg/day for 10 weeks. Although pemafibrate treatment did not change plasma lipid profiles in either WT or eNOSKO mice, pemafibrate reduced plasma AST levels in both WT and eNOSKO mice compared to the levels in the vehicle-treated mice. Histopathological analysis of the liver showed that MASLD was improved in the pemafibrate-treated groups in both WT and eNOSKO mice. Compared to vehicle treatment, pemafibrate treatment significantly reduced the expression levels of hepatic NADPH oxidase subunit genes, M1 macrophages, inflammatory-cytokine-related genes and profibrotic genes in both WT and eNOSKO mice, along with reduction in hepatic oxidative stress assessed by dihydroethidium staining and 4-hydroxynonenal protein levels. Thus, pemafibrate ameliorated MASLD with reduction in oxidative stress and inflammation even in vascular endothelial dysfunction. Full article

Head and neck cancer (HNC) is a highly aggressive malignancy with limited treatment options and poor prognosis. Inflammation plays a critical role in HNC progression, with elevated levels of pro-inflammatory cytokines such as TNF, IL-6, IL-8, and IL-1β contributing to tumor development. In this study, a novel series of boronic chalcones was designed and synthesized as potential dual-action anticancer and anti-inflammatory agents. The most potent compounds were evaluated for their cytotoxicity against Squamous Cell Carcinoma (SCC-25), and their selectivity index (SI) was determined. Compound 5 emerged as the most promising, displaying cytotoxicity against cancer cells, with IC₅₀ values of 17.9 µM and a favorable SI (>3). Mechanistic studies revealed that its anticancer activity was independent of p53 status, and annexin V/PI staining indicated cell death via necrosis. Interestingly, compound 5 also significantly reduced pro-inflammatory cytokine levels, as TNF and IL-6. Furthermore, drug metabolism and pharmacokinetics (DMPK) studies demonstrated that compound 5 exhibited moderate solubility and high permeability. These findings underscore the crucial role of the boronic acid moiety in enhancing both anticancer and anti-inflammatory properties. Full article

In this study, we investigated the expression of TIM-3 and Galectin-9 (Gal-9) in colorectal cancer (CRC) and their associations with oncogenic mutations, MSI status, cytokine profiles, and transcriptional data. TIM-3 and Gal-9 protein levels were significantly increased in CRC tissues compared to matched non-tumor margins (p < 0.05 and p < 0.001, respectively). TIM-3 protein concentration was notably higher in PIK3CA-mutated tumors (p < 0.05), while no associations were found with KRAS, NRAS, BRAF, AKT1, or MSI status. Multiplex cytokine profiling revealed strong correlations between TIM-3 and Gal-9 levels and key immunomodulatory pathways, including IL-10, IL-17, and chemokine signaling. We also observed significant associations with cytokine subsets involved in protumor activity and immune regulation. Gene set enrichment analysis (GSEA) demonstrated that high TIM-3 and Gal-9 expression was associated with upregulation of cell cycle-related pathways, and downregulation of immune signatures, such as interferon responses and TNF-α/NFκB signaling. These findings suggest that increased TIM-3 and Gal-9 expression reflects a shift toward proliferative activity and immune suppression in the CRC tumor microenvironment, highlighting their potential as biomarkers of immunoevasive tumor phenotypes, especially in PIK3CA-mutant CRC tumors. Full article

Endometriosis is the extrauterine engraftment of endometrium-like tissue, causing chronic pain. Complex sensory–vascular–immune interactions, including growth factors, cytokines, and neuropeptides, are implicated in its pathophysiology, but the mechanisms remain unknown. Here, epidermal growth factor (EGF), vascular endothelial growth factor, interleukins (IL-1β, IL-6, IL-8), macrophage migration inhibitory factor (MIF), calcitonin gene-related peptide, and somatostatin were measured in the serum of endometriosis patients with different disease severities, menstruation cycle- and pharmacotherapy-related hormonal status compared with controls. Mediator levels in deep-infiltrating rectosigmoid nodules were also compared with those in non-endometriotic colon tissues. Pain was assessed by the visual analogue scale. Serum EGF was significantly lower in mild endometriosis and in the secretory phase. MIF and IL-6 were higher in stage I–IV endometriosis, with MIF also higher in the secretory phase and in patients not receiving oral contraceptives. Somatostatin was lower in mild endometriosis than that in healthy individuals and the severe endometriosis group. No tissue-level differences were found. A strong positive correlation between serum EGF and somatostatin levels and dysmenorrhea and dysuria was detected in mild cases. It is concluded that certain serum alterations may be related to severity- and hormone status-dependent endometriosis mechanisms, but their diagnostic/prognostic value seems to be limited due to variability and lack of specificity. Full article

Peripheral artery disease (PAD) is associated with an elevated risk of major adverse cardiovascular events (MACE). Despite this, few reliable biomarkers exist to identify patients at heightened risk of MACE. Growth differentiation factor 15 (GDF15), a stress-responsive cytokine implicated in inflammation, atherosclerosis, and thrombosis, has been broadly studied in cardiovascular disease but remains underexplored in PAD. This study aimed to evaluate the prognostic utility of GDF15 for predicting 2-year MACE in PAD patients using explainable statistical and machine learning approaches. We conducted a prospective analysis of 1192 individuals (454 with PAD and 738 without PAD). At study entry, patient plasma GDF15 concentrations were measured using a validated multiplex immunoassay. The cohort was followed for two years to monitor the occurrence of MACE, defined as stroke, myocardial infarction, or death. Baseline GDF15 levels were compared between PAD and non-PAD participants using the Mann–Whitney U test. A machine learning model based on extreme gradient boosting (XGBoost) was trained to predict 2-year MACE using 10-fold cross-validation, incorporating GDF15 and clinical variables including age, sex, comorbidities (hypertension, diabetes, dyslipidemia, congestive heart failure, coronary artery disease, and previous stroke or transient ischemic attack), smoking history, and cardioprotective medication use. The model’s primary evaluation metric was the F1 score, a validated measurement of the harmonic mean of the precision and recall values of the prediction model. Secondary model performance metrics included precision, recall, positive likelihood ratio (LR+), and negative likelihood ratio (LR-). A prediction probability histogram and Shapley additive explanations (SHAP) analysis were used to assess model discrimination and interpretability. The mean participant age was 70 ± SD 11 years, with 32% (n = 386) female representation. Median plasma GDF15 levels were significantly higher in PAD patients compared to the levels in non-PAD patients (1.29 [IQR 0.77–2.22] vs. 0.99 [IQR 0.61–1.63] pg/mL; p < 0.001). During the 2-year follow-up period, 219 individuals (18.4%) experienced MACE. The XGBoost model demonstrated strong predictive performance for 2-year MACE (F1 score = 0.83; precision = 82.0%; recall = 83.7%; LR+ = 1.88; LR− = 0.83). The prediction histogram revealed distinct stratification between those who did vs. did not experience 2-year MACE. SHAP analysis identified GDF15 as the most influential predictive feature, surpassing traditional clinical predictors such as age, cardiovascular history, and smoking status. This study highlights GDF15 as a strong prognostic biomarker for 2-year MACE in patients with PAD. When combined with clinical variables in an interpretable machine learning model, GDF15 supports the early identification of patients at high risk for systemic cardiovascular events, facilitating personalized treatment strategies including multidisciplinary specialist referrals and aggressive cardiovascular risk reduction therapy. This biomarker-guided approach offers a promising pathway for improving cardiovascular outcomes in the PAD population through precision risk stratification. Full article

Background/Objectives: This study aimed to evaluate adipose tissue dysfunction, assessed through adipocytokines and proinflammatory cytokines, in relation to hepatic steatosis (HS) in patients with newly diagnosed type 2 diabetes (T2D). Methods: An observational study evaluated 155 consecutive patients with new-onset T2D; 118 (76.1%) were found to have HS, while the remaining 37 served as the control group without steatosis. Anthropometric status and body mass index (BMI) were evaluated. The biochemical assessment encompassed the measurements of fasting serum lipids, fasting plasma glucose (FPG), liver function tests, adiponectin, leptin, resistin, tumor necrosis factor (TNF-α), and interleukin 6 (IL-6). Insulin resistance (IR) was determined using the homeostasis model assessment (HOMA). HS was evaluated using ultrasonographic criteria. Quantitative evaluation of HS was performed by calculating the hepatic steatosis index (HSI). Results: There were statistically significant differences between the groups for age, BMI, weight, waist circumference (WC) and hip circumference, HSI, glucose profile (fasting plasma glucose (FPG), HOMA-IR), liver function tests, adiponectin, leptin, resistin, TNF-α, and IL-6. In multivariate logistic regression analysis, age, smoking, BMI, WC, HOMA-IR, and hypoadiponectinemia were the only independent factors associated with HS. Conclusions: The adipose tissue dysfunction assessed through adipocytokines and proinflammatory cytokines is part of the associated disorders in HS and new-onset T2D. In patients with newly diagnosed T2D, age, smoking, and hypoadiponectinemia consistently emerged as independent predictors of hepatic steatosis. More prospective trials are needed to clarify the “the temporal onset” of adipose tissue dysfunction. Full article

Identifying immunologic predictors of clinical responses remains an unmet need in the era of biologic therapy for psoriasis. Super responders (SRs), defined as patients achieving complete skin clearance within weeks of treatment initiation, represent an emerging clinical endotype; however, their immunological profiles remain insufficiently characterized. We conducted a prospective observational study to characterize serum cytokine profiles associated with SR status in biologic-naïve patients with moderate-to-severe plaque psoriasis treated with secukinumab, an IL-17A inhibitor. Twenty-eight patients were enrolled and stratified at week 12 into SR (PASI = 0; n = 9) and non-super responder (NSR; PASI > 0; n = 19) groups. Serum concentrations of 19 cytokines were analyzed at baseline and after 12 weeks of treatment. SRs displayed a distinct immunological signature characterized by significantly higher IL-13 and lower IL-18 baseline levels compared to NSRs (p = 0.002 and p = 0.007, respectively), alongside reduced baseline monocyte counts. L1-regularized logistic regression confirmed IL-13 and IL-18 as strong independent predictors of SR status (AUC = 0.91). Moreover, the IL-18/IL-13 ratio emerged as a highly discriminative biomarker (p = 0.00001, AUC = 0.86). Notably, SRs exhibited a more pronounced decline in IL-18 and IL-23 during treatment. Our findings provide novel insights into the immunopathogenesis of super response and suggest that an immunological milieu favoring Th2 polarization may promote superior outcomes with IL-17A blockade. Incorporating IL-13, IL-18, and their ratio into clinical algorithms may facilitate precision-guided biologic therapy in psoriasis. Full article