Search Results (99)

Background: The immunological factors associated with long-term hepatitis C virus (HCV)-specific humoral immunity after cure remain uncharacterized, particularly in people with HIV (PWH). This study investigated T-cell immunophenotypes and plasma biomarkers associated with anti-E2 binding (HCV-E2Abs) and neutralizing antibody (HCV-nAbs) titers 5 years after achieving sustained virologic response (SVR). Methods: This cross-sectional study analyzed 64 PWH with cured HCV and prior advanced fibrosis. We quantified plasma antibody titers against 5 HCV genotypes, T-cell phenotypes (n = 58), and plasma biomarkers (n = 50). Associations were assessed using Generalized Linear Models (gamma distribution, log-link function) adjusted for clinical confounders, reporting adjusted Arithmetic Mean Ratios (aAMRs) and false discovery rate (FDR)-corrected q-values. Results: Higher frequencies of CD4⁺ T-cell activation (CD38⁺; aAMR = 1.58; q = 0.028) and soluble CD27 levels (aAMR = 1.46; q = 0.038) were associated with higher HCV-E2Abs titers. In contrast, memory T-cell activation across CD4⁺ and CD8⁺ compartments (HLA-DR⁺ and CD38+; all q < 0.10) and elevated soluble immune checkpoints (sCD28, sPD-L2, sLAG-3, sCTLA-4; all q < 0.10) were associated with preserved HCV-nAbs titers. Conversely, a higher frequency of naïve CD8⁺ T-cells was associated with lower neutralization capacity (aAMR = 0.41; q = 0.042). Regarding inflammatory markers, soluble TNF-RI was positively associated with neutralizing titers (aAMR = 1.44; q = 0.019), whereas IL-18 was inversely associated (aAMR = 0.53; q = 0.019). Conclusions: Specific activated T-cell subsets, checkpoint shedding, and selective inflammatory signals were associated with higher long-term HCV-nAbs titers in PWH. In contrast, higher frequencies of naïve CD8⁺ T-cells and elevated IL-18 levels were associated with reduced neutralizing capacity. Full article

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. Full article

This study aimed to investigate the anti-allergic potential of the ethyl acetate fraction (EtOAc) from Phyllanthus amarus using an ovalbumin (OVA)-induced allergic mouse model and in vitro RBL-2H3 mast cell assays. The EtOAc fraction was characterized by high total phenolic and flavonoid contents, reaching 261 ± 18 mg GAE/g EtOAc fraction and 86 ± 7 mg QE/g EtOAc fraction, respectively. It was found that EtOAc fraction significantly reduced histamine release up to 43.3% and suppressed reactive oxygen species (ROS) production from FcɛRI-mediated mast cell activation at a concentration treatment of 200 µg/mL. Furthermore, EtOAc fraction decreased interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) release up to 94.2 pg/mL and 195.6 pg/mL, respectively. In the OVA-induced allergic mouse model, EtOAc fraction treatment markedly lowered sneezing frequency and serum IgE and histamine levels by approximately 50% at a dose treatment of 50 mg/kg. In addition, histopathological analysis revealed that the EtOAc fraction significantly alleviated inflammatory cell infiltration, particularly eosinophils, in lung tissue. Accordingly, the results highlight the potential of EtOAc fraction from P. amarus as a natural candidate for managing allergic diseases. Full article

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. Full article

Heat stress-induced systemic metabolic disorder serves as the core pathological basis of organismal damage. Although mung bean polyphenols (MBPs) had been preliminarily validated in cellular heat-stress models for their intestinal tissue-protective potential, whether they can alleviate heat-stress injury in vivo by remodeling the metabolic crosstalk network between the gut and systemic circulation remains mechanistically unclear. In this study, we innovatively employed an integrated multi-omics approach combining physiological phenotype, gut metabolome, and serum metabolome analyses based on a Balb/c heat stress (41 °C) mouse model, systematically constructing the metabolic phenotype regulatory network of MBPs. The results demonstrated that MBPs not only significantly improved oxidative stress (elevating GSH-Px and T-AOC, reducing MDA), immune-inflammation (down-regulating IL-1β and TNF-α), and stress hormone (lowering cortisol) phenotypes, but also specifically reversed the disturbances in intestinal and serum metabolic profiles induced by heat stress, particularly restoring key pro-inflammatory mediators such as Leukotriene E4 and 5-HETE. Arachidonic acid metabolism, tryptophan metabolism, histidine metabolism, and Fc epsilon RI signaling pathway constituted the core network of heat-stress metabolic disorder and MBP regulation. Furthermore, the study revealed that alterations in hub metabolites—Indolelactic Acid, Trans-Cinnamic Acid, Leukotriene E4, 5-HETE, and N(omega)-Hydroxyarginine—were significantly correlated with phenotypic improvements. This confirms that mung bean polyphenols dynamically dismantle the “pro-inflammatory-oxidative stress” pathological coupling by constructing a novel protective axis centered on the indole metabolism–melatonin–endogenous antioxidant system and successfully established a novel protective axis driven by gut-derived beneficial metabolites that promotes systemic antioxidant function, thereby elucidating the systemic mechanism underlying the alleviation of heat-stress injury at the metabolic network level. Full article

Diabetes mellitus disrupts bone homeostasis, inducing bone fragility, through mechanisms involving chronic inflammation and altered cellular signaling. Osteocytes, the primary mechanosensory cells in bone, play a pivotal role in regulating bone remodeling via the secretion of factors that influence both osteoclast and osteoblast activity. We investigated the impact of high glucose on osteocytic parathyroid hormone receptor type 1 (PTH1R) expression and its downstream effects on interleukin-6 (IL-6) secretion, macrophage polarization, and osteoclastogenesis. Using both in vitro and ex vivo bone models, we demonstrate that elevated glucose levels in static conditions without mechanical stimulation induce the overexpression of PTH1R in osteocytes. PTH1R upregulation in turn enhances osteocytic IL-6 secretion associated with the promotion of a pro-inflammatory macrophage M1 phenotype (increased tumor necrosis factor (TNF)-$\alpha$/CD206 and inducible nitric oxide synthase (iNOS)/CD206 ratios) and the upregulation of the pro-osteoclastogenic markers tartrate-resistant acid phosphatase (TRAP) and receptor activator of nuclear factor kappa-Β (RANK). Neutralization of IL-6 in the osteocytic secretome attenuated macrophage inflammatory gene overexpression, underscoring IL-6’s critical role in this regulatory axis. Our findings reveal that a high-glucose environment triggers osteocytic dysregulation of PTH1R-mediated signaling pathways, amplifying inflammatory and osteoclastogenic activity in bone via IL-6. This osteocyte–macrophage crosstalk may contribute to the increased bone resorption and impaired regeneration observed in diabetic bone disease. Targeting PTH1R upregulation and the IL-6 signaling pathway in osteocytes could represent a novel therapeutic approach to mitigating bone complications associated with diabetes. Full article

Background and Objectives: IgG4-related disease is a chronic fibro-inflammatory condition. Despite the development of classification and responder indexes, reliable biomarkers for disease activity and therapeutic monitoring remain limited. We evaluate the performance of a panel of biomarkers, including cytokine profiles, plasmablasts and conventional markers. Materials and Methods: We conducted a cross-sectional, single-center study, involving 35 patients diagnosed with IgG4-RD. Disease activity was evaluated using the IgG4-RD Responder Index (RI), Damage Index (DI) and clinical assessment. Laboratory evaluation included serum IgG4, total IgG, CRP, ESR, eosinophils, IgE, complement levels, and cytokine profiling via multiplex immunoassay. B cell subpopulations were analyzed by flow cytometry. Statistical analyses were performed using STATA/BE 17.0. Results: Patients with active disease (RI > 4 or clinical judgment) exhibited significantly higher levels of total IgG (p = 0.02), IgG4 (p = 0.01), and IL-5 (p = 0.03). PET-positive patients showed a Th1-skewed immune profile, with elevated IFN-γ/IL-4 (p < 0.001), reduced IL-21/IFN-γ (p = 0.03), and increased eosinophils (p = 0.03). Clinician-assessed active disease was associated with higher total IgG levels (p = 0.01). Treatment-specific effects were observed: prednisone was associated with lower IgG4 and C3 levels. Notably, plasmablasts did not consistently correlate with clinical or imaging activity scores, possibly reflecting treatment status or B cell dynamics. Conclusions: This study demonstrates that cytokine ratios, particularly those involving IL-5, IL-13, IL-21, and IFN-γ, offer complementary information to traditional serological markers for IgG4-RD activity. While PET/CT-defined activity was best reflected by biomarkers of an IFN-γ-mediated pathway, the IgG4-RD RI demonstrated a stronger association with conventional humoral markers like serum IgG4 and total IgG. None of these biomarkers correlated with organ damage. Full article

Tumor tissue is surrounded by mast cells (MCs), which participate in the inflammatory immune response by producing cytokines, proteases, and other molecules. MCs are involved in both innate and acquired immunity and are associated with the IgE response through the FcεRI receptor. MCs mediate inflammation in several immune reactions, including acute hyperreactivity, leukocyte recruitment, acute tissue swelling, anaphylaxis, and pro-inflammatory cytokine production. They not only function as pro-inflammatory effector cells but may also contribute to the regulation of the acquired immune response in tumor tissue. Therefore, MCs may mediate immunity in breast cancer by promoting remodelling and counteracting cancer growth. They also produce anti-inflammatory substances, such as histamine, transforming growth factor-β (TGF-β)1, IL-10, and IL-4, which inhibit the acquired immune response and reduce the inflammatory state. IL-37 and IL-38 are novel natural regulators of inflammation and are anti-inflammatory members of the IL-1 family. IL-1, generated by immune cells such as macrophages and lymphocytes, is released downstream of oncogenes in breast cancer, triggering an inflammatory response by stimulating other pro-inflammatory cytokines such as IL-6, tumor necrosis factor (TNF), and IL-33 (an early warning cytokine). Therefore, blocking IL-1 with IL-37 or IL-38 could represent a novel therapeutic strategy that, when combined with other treatments, could be beneficial in breast cancer. This review focuses on the new discoveries and insights into the role of MCs in breast cancer. We also analyzed molecules that can promote tumor growth and those that can inhibit cancer development and metastasis. This review aims to study the role of MCs accumulated in the stroma of breast adenocarcinoma in relation to secreted anti-inflammatory cytokines, such as IL-37 and IL-38. Full article

Background: Neuromyelitis optica spectrum disorder (NMOSD) involves demyelinating astrocytopathy. Most cases have autoantibodies against aquaporin-4 (AQP4 ab), but AQP4 ab-negative patients may also meet NMOSD criteria. Overlapping clinical phenotypes of CNS inflammatory demyelinating diseases (IDDs) complicate understanding NMOSD mechanisms. Objectives: Investigate molecules related to neuroinflammation and astrocyte function as potential biomarkers of NMOSD and other IDDs by using clinical data and in vitro assays. Methods: Subjects (176) with different IDDs (NMOSD (37), MS (125), MOGAD (3), ADEM (3) and eight radiologic isolated syndromes (RIS)) were studied. Plasma concentrations of TGF-β and other cytokines were measured by single molecule array (SIMOA), Luminex and ELISA assays. Functional assays used in vitro cultured human astrocytes exposed to NMOSD subjects’ serum, followed by immunolabeling. Results: TGF-β levels were higher in NMOSD patients during attacks compared to inactive phases. AQP4+ groups in inactive phases had lower TGF-β levels than AQP4− groups. No significant difference was found for IL-1β, IL-8, IL-10, IL-17A and Thrombospondin plasma concentrations, with a minor difference for VEGF in the AQP4+ group. Astrocytes exposed to NMOSD AQP4+ and AQP4− subjects serum, with or without TGF-β1, showed no changes in C3, NFkB and HMGB1. However, the content of GLT-1 decreased in AQP4+ serum-treated astrocytes, reversed by TGF-β1. Conclusions: TGF-β may be a potential NMOSD activity biomarker, indicating different disease mechanisms based on AQP4 ab presence. Full article

The actinobacterial strain Kitasatospora griseola JNUCC 62 was isolated from volcanic wetland soil at Mulyeongari Oreum, Jeju Island, and taxonomically identified through 16S rRNA gene and whole-genome analyses. The complete genome, assembled from PacBio Sequel I reads, spans 8.31 Mb with a GC content of 72.8% and contains 7265 coding sequences. Comparative genomic indices (Average nucleotide identity, ANI 97.46%; digital DNA–DNA hybridization, dDDH 84.4%) confirmed its conspecific relationship with K. griseola JCM 3339^T. Genome mining using antiSMASH 8.0 revealed 30 biosynthetic gene clusters (BGCs), including polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), ribosomally synthesized and post-translationally modified peptide (RiPP), lanthipeptide, and terpene types, accounting for 18.6% of the genome. Several BGCs displayed homology to known formicamycin-, lankacidin-, and lanthipeptide-type clusters, while others were novel or cryptic, reflecting adaptation to the nutrient-poor volcanic environment. Ethyl acetate extraction of the culture broth, especially under tryptophan-supplemented conditions, yielded four metabolites—1-acetyl-β-carboline, perlolyrine, tryptopol, and 1H-pyrrole-2-carboxylic acid—identified by UV and NMR spectroscopy. These compounds correspond to NRPS–PKS hybrid and arylpolyene-type gene clusters predicted in the genome, suggesting precursor-directed biosynthesis of indole and pyrrole alkaloids. The ethyl acetate extract (JNUCC62 EA) exhibited strong antioxidant capacity in the ABTS assay, anti-inflammatory activity via inhibition of nitric oxide (31.09 ± 3.69% of control) and cytokines (IL-6, IL-1β, TNF-α) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and anti-melanogenic effects in α-melanocyte-stimulating hormone (MSH)-stimulated B16F10 melanoma cells, where melanin content and tyrosinase activity decreased to 61.49 ± 1.24% and 24.32 ± 0.31% of the control, respectively, without cytotoxicity. A human primary skin irritation test confirmed no irritation up to 50 µg/mL, establishing excellent dermal safety. Collectively, these findings highlight K. griseola JNUCC 62 from Mulyeongari Oreum as a volcanic wetland-derived actinomycete harboring rich biosynthetic potential for novel indole alkaloids with antioxidant, anti-inflammatory, and whitening properties, supporting its development as a safe and multifunctional cosmeceutical ingredient. Full article

AMP-activated protein kinase (AMPK) acts as a cellular energy sensor and a central regulator of metabolism. Recent studies indicate that pharmacological AMPK activation can simultaneously ameliorate metabolic disorders (e.g., type II diabetes, obesity) and allergic diseases. Zingerone, a primary bioactive compound in ginger, demonstrates protective effects in vascular calcification, non-alcoholic fatty liver disease, and asthma via AMPK activation. This study aimed to evaluate the anti-allergic activity of Zingerone and elucidate its AMPK-dependent mechanisms. In vitro, Zingerone suppressed FcεRI-mediated phosphorylation of PLCγ1, Akt, ERK1/2, JNK, p38, and IKK, while reducing β-hexosaminidase release, eicosanoid (LTC₄/PGD₂) generation, pro-inflammatory cytokine (TNF-α/IL-6) secretion, and Ca²⁺ influx through LKB1/AMPK activation. In vivo, Zingerone (25–50 mg/kg, oral) attenuated passive cutaneous anaphylaxis (reduced Evans blue extravasation) and systemic anaphylaxis (inhibited histamine/LTC₄/PGD₂ release). These findings demonstrate that Zingerone inhibits FcεRI-dependent mast cell activation and anaphylaxis via the LKB1/AMPK pathway, highlighting its therapeutic potential for mast cell-mediated allergic diseases. Full article

Background/Objectives: Individual plasma protein biomarkers have been shown to correlate with cognitive performance in people with HIV (PWH). This study aimed to investigate the association between plasma proteomic signatures and attention/working memory in virologically well-controlled women with HIV (WWH). Methods: Seventy-seven WWH from three Women’s Interagency HIV Study (WIHS) sites completed neuropsychological (NP) testing and a blood draw. Selected protein biomarkers (200 total) were analyzed using a multiplexing method. Results: Random forest analysis was used to identify the top 10 biomarkers that were each positively or negatively associated with attention/working memory. Ingenuity pathway analysis (IPA) was used to facilitate data interpretation. Tumor necrosis factor receptor 1 (TNF RI), TNF RII, interleukin 1 receptor 1 (IL-1RI), and IL-6R were negatively associated with attention/working memory. Conclusions: Based on the IPA, two gene signaling networks were proposed for associating these plasma protein biomarkers with attention/working memory function. This novel methodology demonstrates how gene networks can be identified using blood draws in conjunction with cognitive assessment, and then used in random forest analysis, to derive value that can be put in IPA. Full article

Biologics targeting tumor necrosis factor-α (TNFi), interleukin-12/23 (IL-12/23i), and interleukin-17 cytokine or receptor (IL-17i/IL-17Ri) have transformed psoriasis management. However, interindividual variation in response underscores the need for predictive biomarkers in guiding therapy selection. Patients treated with a biologic for psoriasis were genotyped for 67 single-nucleotide polymorphisms (SNPs) previously associated with response to biologics. Odds ratios (OR) with 95% confidence intervals (CI) for associations between SNPs and response to biologics were calculated using logistic regression models with an absolute Psoriasis Area and Severity Index (PASI) ≤2 after 3 months as treatment response. A p-value < 0.05 was considered statistically significant. In total, 373 patients with 574 treatment series were included. Twelve SNPs were associated with treatment response: four uniquely with response to TNF inhibitors (TNFi), two to IL-12/23i, and five to IL-17i/IL-17Ri, while one was associated with response to both TNFi and IL-17i/IL-17Ri. Notably, IRAK3 (rs11541076) and CD84 (rs6427528) were associated with response to TNFi (OR: 2.56 [95% CI: 1.22–5.37], p = 0.012 and OR: 0.53 [95% CI: 0.30–0.91], p = 0.023) and IL-17i/IL-17Ri (OR: 2.55 [95% CI: 0.70–9.22], p = 0.15), and OR: 0.50 [95% CI: 0.25–0.98], p = 0.045), with trends toward opposite associations for IL-12/23i (OR: 0.38 [95%CI: 0.08–1.72], p = 0.21 and OR: 1.64 [95%CI: 0.68–3.93], p = 0.26). This study replicates known genetic associations with biologic response in psoriasis. Variants in IRAK3 and CD84 show potential as stratification biomarkers, although they need confirmation in independent cohorts. Full article

Background and Objectives: SARS-CoV-2 infection initiates at mucosal surfaces, and mucosal immunity may influence the nature and severity of infection. Little is known about the induction of mucosal immunity by vaccination in COVID-19 convalescents. Methods: Sera from 205 healthcare workers were collected one month after the first Covishield vaccination and 1/3/6 months after the second vaccination, while paired sera and stimulated whole-mouth fluid (SWMF) was collected 1/3/6 months after the third vaccination (N = 10) and at 0/30/90 days after a COVID-19 episode (N = 8). Anti-SARS-CoV-2 spike antibody detection by ECLIA/ELISA and cytokine detection by ELISA/CBA were performed. Results: One month post-second vaccination, serum antibodies had increased significantly (6-fold) in the COVID-19-naïve group (CNG) but declined (1.5-fold) in the previously COVID-19-exposed group (CEG), who already had high antibody titres. The serum regulatory cytokine IL-10 levels were higher after three antigen exposures (p = 0.0002). New infections (breakthrough infections—BTIs) or reinfections (RIs) with asymptomatic/mild disease occurred in 44% of the CNG and 27% of the CEG (p < 0.01). The mucosal cytokine IL-17 levels were significantly higher in the CEG. Salivary IgG/IgA and secretory IgA antibodies were detectable both after vaccination and COVID-19. Innate cytokines (MIG, MCP-1, IL-8, IL-1β) were higher and sustained in SWMF in contrast to serum. Conclusions: Two vaccinations in the CNG resulted in an antibody boost, but the second vaccination in the CEG induced antibody anergy. Serum/mucosal antibodies declined by six months after vaccination, but the rapid increase at subsequent exposures were indicative of a good T cell/B cell memory response to SARS-CoV-2. A higher percentage of BTI among the CNG than RI among the CEG may indicate better protection due to higher antibody responses in the latter group. Full article

Background: Preterm birth (PTB) remains the leading cause of neonatal morbidity and mortality worldwide, with approximately two-thirds of cases occurring spontaneously (SPTB), but the etiology is still poorly understood. Chronic inflammatory diseases, such as periodontitis (PD), have been considered SPTB risk factors. However, we hypothesized that SPTB may instead represent a clinical manifestation of a broader genetic predisposition to dysregulated inflammation. Using PD as a model of chronic inflammation, we examined shared genetic susceptibility. Methods: In a case–control study (N = 126 Portuguese postpartum women), we screened 56 SNPs in 36 inflammation-related genes. Four functionally plausible variants (IL1RN rs4251961, TLR1 rs5743618, IL6 rs2069827, and IL6R rs4845617) were selected for detailed regression, adjusting for gestational age, floss usage, and an SPTBxPD interaction term. Results: IL1RN rs4251961 was recessively associated with SPTB risk, consistent with reduced IL-1RA expression linked to this variant. IL6R rs4845617 showed a modest protective effect. TLR1 rs5743618 exhibited the strongest association with the composite “inflammation” phenotype under multiple models, with CC homozygotes showing four-fold increased odds, independent of SPTB/PD co-occurrence. Conclusions: This study provides original evidence that shared genetic variants in inflammatory pathways—particularly TLR1 rs5743618—may underlie susceptibility to SPTB and PD. Our findings suggest a paradigm shift, viewing SPTB as a possible outcome of systemic inflammatory dysregulation rather than merely a consequence of comorbid inflammatory conditions. Future studies should validate this marker in larger cohorts. Full article