Search Results (100)

Background: Pancreas and pancreas–kidney transplantation are well-established therapeutic options for patients with type 1 diabetes mellitus (T1DM) and end-stage kidney disease (ESKD), offering the potential to restore endogenous insulin production and kidney function. It improves metabolic control, quality of life, and long-term survival. While surgical techniques and immunosuppressive strategies have advanced considerably, graft rejection and limited long-term graft survival remain significant clinical challenges. Method: To better understand these risks, the genetic and immunological factors that influence transplant outcomes are examined. Beyond traditional human leukocyte antigen (HLA) matching, non-HLA genetic variants such as gene deletions and single-nucleotide polymorphisms (SNPs) have emerged as contributors to alloimmune activation and graft failure. Result: Polymorphisms in cytokine genes, minor histocompatibility antigens, and immune-regulatory pathways have been implicated in transplant outcomes. However, the integration of such genomic data into clinical practice remains limited due to underexplored gene targets, variability in study results, and the lack of large, diverse, and well-characterized patient cohorts. Initiatives like the International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) are addressing these limitations by aggregating genome-wide data from thousands of transplant donors and recipients across multiple centers. These large-scale collaborative efforts aim to identify clinically actionable genetic markers and support the development of personalized immunosuppressive strategies. Conclusions: Overall, genetic testing and genomics hold great promise in advancing precision medicine in pancreas and pancreas–kidney transplantation. Full article

The mammalian immune system, including key components such as toll-like receptors (TLRs), lymphocytes, and cytokines, plays a vital role in defending against diseases. In dogs, genetic polymorphisms and epigenetic regulation of immune-related genes contribute to breed-specific differences in susceptibility or resistance to infectious, autoimmune, and inflammatory diseases. Cytokines, essential for immune cell differentiation and activation, exhibit variable expression among breeds due to genetic factors like single-nucleotide polymorphisms (SNPs) and miRNA regulation. This variability influences immune responses not only to infections but also to chronic inflammatory conditions and cancer, providing insights for improved diagnosis, treatment, and breeding. Selective breeding has further shaped diverse immune phenotypes across breeds, especially through genetic variations in the major histocompatibility complex (MHC) region, which affect vulnerability to immune-mediated and immunodeficiency disorders. Recent studies emphasize the role of specific miRNAs in modulating immune responses during parasitic and viral infections, opening new avenues for precision veterinary medicine and immunotherapy. This review highlights the genetic and epigenetic regulation of immune genes in dogs and explores their potential applications in advancing veterinary diagnostics, therapeutics, and breeding strategies to enhance canine health. Full article

Background: Ankylosing Spondylitis (AS) is a rare autoinflammatory disorder affecting 0.1–1.4% of the population, with increasing recognition over the past 20 years. Although the specific causes of AS remain unclear, the presence of the HLA-B27 gene is associated with increased risk, though only 1–5% of carriers develop the disease. Despite extensive research, no definitive lab tests exist, and many patients are diagnosed years after symptom onset. Methods: In the present study, in order to investigate the disease’s genetic background in correlation with autoimmune diseases, a metanalysis has been performed following PRISMA guidelines using Scopus and PubMed publications towards extracting single-nucleotide polymorphisms (SNPs) of high importance for the disease. Moreover, the polymorphisms have been annotated and analyzed using information from several databases, including PubMed, LitVar2, ClinVar, and Gene Ontology. Results: From 1940 screened titles and abstracts, 57,909 studies were selected, with 539 meeting the inclusion criteria. The genetic background of AS is described through 794 genetic variants, of which 76 SNPs are directly associated with AS (Classes A and B), predominantly located in intronic regions. ERAP1 and IL23R emerged as key genes implicated in AS, while chromosomes 1, 2, and 5 accumulated the most associated SNPs. Functional enrichment revealed strong associations with immune regulation and interleukin signaling pathways, particularly IL6 and IL10 signaling. IL-6 promotes inflammation in AS, while IL-10 tries to suppress it, acting as an anti-inflammatory cytokine. Of the 78 AS-related SNPs, 16 were unique to AS, while 66 were common to autoimmune diseases, especially rheumatoid arthritis (RA) and psoriasis (PsO), suggesting genetic overlap between these diseases. Conclusions: This study creates a comprehensive genetic map of AS-associated SNPs, highlighting key pathways and genetic overlap with autoimmune diseases. These findings contribute to understanding disease mechanisms and could guide therapeutic interventions, advancing precision medicine in AS management. Full article

Fish are rich sources of amino acids (AAs), particularly human essential amino acids (HEAAs). Exploring the regulatory mechanisms behind the changes in the combined AA content in the fillet and enhancing the content of AAs, especially HEAAs, in fillets of farmed fish is crucial for meeting human nutritional needs. After hot acidic hydrolysis of 304 common carp fillets, we quantified the contents of 17 single AAs and 5 AA groups and observed significant variations among them. Except for Pro, 16 single AAs and all AA groups showed medium-to-high heritabilities over 0.2. Through a genome-wide association study (GWAS), we identified 1974 SNPs and candidate genes associated with at least one AA content. Using transcriptome data from groups with the highest and lowest contents for each AA, 7089 candidate genes were related to the concentrations of at least two AAs. For the total HEAA content, 121 SNPs and their associated genes preferred ATPase-coupled transmembrane transporter activity, and 4727 differentially expressed genes were enriched in cytokine activity, chemokine activity, oxidoreductase activity, and ion binding. With the optimal genomic selection programs and associated SNPs, the correlation between the actual AA contents and estimated breeding values was high and positive, ranging from 0.76 to 0.90. These findings revealed the major-effect processes and regulatory mechanisms modulating the differences in fillet AA contents. The genomic selection programs will guide the future selection of common carp with high AA contents. Full article

Background/Objectives: Tumor necrosis factor alpha (TNF-α) is the key inflammatory cytokine involved in the pathogenesis of inflammatory bowel diseases (IBDs). Anti-TNF-α therapy has been successfully used for IBD treatment, although the therapeutic response differs among patients due to the genetic background. The aim of this study was to investigate whether the presence of single nucleotide polymorphisms (SNPs) on TNFA, TNFRSF1A, and TNFRSF1B genes could affect anti-TNF-α treatment effectiveness in IBD patients. Methods: In this prospective cohort study, 83 European IBD patients treated with infliximab or adalimumab (with or without steroid bridge therapy) as first-line therapy were enrolled. Genomic DNA was extracted from peripheral blood, and TNF-α (rs1800629, rs361525, rs1799724), TNFRSF1A (rs767455), and TNFRSF1B (rs1061622, rs1061624, rs3397, rs976881) SNPs were assessed. Steroid-free remission (SFR) (clinical remission together with steroid interruption) and anti-TNF-α therapy persistence after 12 months of follow-up were evaluated. Patients who stopped anti-TNF-α therapy before the end of follow-up, due to side effects or treatment failure, were defined as discontinuers. Results: A higher frequency of the G/G genotype in rs1800629 and the A/A genotype in rs1061624 was observed in the SFR group compared to non-SFR (97.7% vs. 82.8%; p = 0.025 and 32.6% vs. 10.3%; p = 0.029, respectively). Moreover, carriers of the A/A genotype in rs361525 and the C/C genotype in rs767455 had a lower probability of achieving SFR than wild-type patients (OR = 0.14; 95% CI= 0.03–0.69; p = 0.016 and OR = 0.10; 95% CI = 0.02–0.60; p = 0.012, respectively). Furthermore, an increased frequency of rs1800629 A allele was observed in patients who discontinued treatment compared to completers (27.3% vs. 6.9%; p = 0.033), as well as a high risk of interrupting therapy (HR = 6.47; 95% CI = 1.15–36.38). Conclusions: These results suggest that the evaluation of SNPs in TNF-α, TNFR1A, and TNFR1B genes could improve the management of IBD, leading to more effective, individualized treatment plans and a reduction in healthcare costs associated with ineffective therapies and disease complications. Full article

The pathogenesis of the central nervous system (CNS) pathology in tick-borne encephalitis (TBE) remains unclear. We attempted to identify mediators of the blood–brain barrier (BBB) disruption in human TBE in paired serum and cerebrospinal fluid (CSF) samples from 100 TBE patients. CSF albumin quotient (Q_alb) was calculated as a measure of BBB impairment. Concentrations of cytokines, cytokine antagonists, adhesion molecules, selectins and matrix metalloproteinases (MMP) were measured with a multiplex bead assay. Single nucleotide polymorphisms (SNP) in genes MIF, TNF, TNFRSF1A, TNFRSF1B, IL-10, TLR3 and TLR4 were studied in patient blood DNA extracts and analyzed for associations with Q_alb and/or cytokine concentrations. The multivariate regression models of Q_alb were built with the soluble mediators as independent variables. The best models obtained included L-selectin, P-selectin, sVCAM, MMP7, MMP8 (or MMP9) and IL-28A as positive and IL-12p70, IL-15, IL-6Rα/IL-6 ratio and TNF-RII/TNFα ratio as negative correlates of Q_alb. The genotype did not associate with Q_alb, but polymorphism rs4149570 (in TNFRSF1A) associated with TNFα and rs1800629 (TNF) with MIF concentration. We confirm the association of the TNFα-dependent response, L-selectin and MMP8/MMP9 with BBB disruption and identify its novel correlates (IL-12, IL-15, IL-28A, MMP7). We detect no genotype associations with BBB function in TBE. Full article

Recently a resurgence of Streptococcus pyogenes infections has arisen, with concerns around the highly virulent M1_UK lineage. Our aim was to characterize S. pyogenes, the immune responses it causes, and to determine the presence of the M1_UK lineage in Sofia, Bulgaria. In our study, the infections were confirmed by culture testing or rapid antigen test. Identification was performed by MALDI-TOF and was followed up by antibiotic susceptibility testing (EUCAST). Virulence factors were identified using multiplex PCR and whole genome sequencing (WGS). Immune responses were measured through detection of serum complement levels, lymphocyte subsets, and cytokine profiling. Out of 82 children, 38 had scarlet fever and the rest had streptococcal pharyngitis. Strains were susceptible to penicillin (β-lactams), macrolides, clindamycin, tetracyclines, co-trimoxazole, fluoroquinolones, and linezolid. Superantigen profiles were identified: SpeA + SpeJ (45%), SpeC, and SpeI + SpeH (27.5% each). A novel Multilocus sequence typing (MLST) haplotype in the mutS gene (d90b) was found in four strains. The M1_UK lineage was detected for the first time in Bulgaria. We observed an increase in complement fractions C3 and C4 and a decrease in T lymphocytes. A significant increase in the levels of IFN-γ, IL-6, and IL-10 with corresponding reduction in IL-17A were revealed. In conclusion, the studied S. pyogenes strains were characterized by their susceptibility to antibiotics and the predominance of SpeA superantigen; for the first time in Bulgaria the presence of M1_UK and a novel SNP variation in the mutS gene (d90b) were found. A mixed pattern of pro- and anti-inflammatory immune responses in patients was observed. Full article

Background/Objectives: Unrelated bone marrow transplantation (BMT) is a curative treatment for hematological malignancies. While HLA mismatch is a recognized risk factor in unrelated BMT, the significance of non-HLA single nucleotide polymorphisms (SNPs) remains uncertain. Cytokines play key roles in several aspects of unrelated BMT. Although the relationship between cytokine gene SNPs and BMT outcomes has been examined, the findings obtained have been inconsistent; therefore, further investigations in additional cohorts are warranted. Methods: Four SNPs in the IL2, IL6, IFN-gamma, and TGF-beta1 genes were retrospectively genotyped in 822 malignant patients and their corresponding donors who received unrelated BMT through the Japan Marrow Donor Program with compatibility at minimum HLA-A, -B, and -DRB1. The relationships between these SNP genotypes and BMT outcomes were statistically analyzed. Results: The donor interleukin-6 (IL6) SNP, rs1800796, also known as -572G>C and -634C/G, was associated with the relapse of the original disease in both univariable and multivariable regression analyses (minimum p-value = 0.0013), and the cumulative incidence curve analysis identified CC as a risk genotype (p-value = 0.0012). None of these SNPs correlated with overall survival. Conclusions: The donor IL6 SNP, rs1800796, may serve as a useful predictor of tumor relapses if validated. Full article

Coronary artery disease (CAD) is the most prevalent form of cardiovascular disease. A growing body of research shows that interleukins (ILs), such as IL-8, IL-18 and IL-16, elicit pro-inflammatory responses and may play critical roles in the pathologic process of CAD. Single nucleotide polymorphisms (SNPs), capable of generating functional modifications in IL genes, appear to be associated with CAD risk. This study aims to evaluate the associations of ten previously identified SNPs of the three cytokines with susceptibility to or protection of CAD. A systematic review and meta-analysis were conducted using Pubmed, EMBASE, WOS, CENTRAL, CNKI, CBM, Weipu, WANFANG Data and Google Scholar databases for relevant literature published up to September 2024. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the four genetic models of the investigated SNPs in overall and subgroups analyses. Thirty-eight articles from 16 countries involving 14574 cases and 13001 controls were included. The present meta-analysis revealed no significant association between CAD and IL-8-rs2227306 or five IL-16 SNPs (rs8034928, rs3848180, rs1131445, rs4778889 and rs11556218). However, IL-8-rs4073 was significantly associated with an increased risk of CAD across all genetic models. In contrast, three IL-18 (rs187238, rs1946518 and rs1946519) variants containing minor alleles were associated with decreased risks of CAD under all models. Subgroups analyses by ethnicity indicated that IL-8-rs4073 conferred a significantly higher risk of CAD among Asians, including East, South and West Asians (allelic OR = 1.46, homozygous OR = 1.96, heterozygous OR = 1.47, dominant OR = 1.65), while it showed an inversely significant association with CAD risk in Caucasians (homozygous OR = 0.82, dominant OR = 0.85). Additionally, IL-18-rs187238 and IL-18-rs1946518 were significantly associated with reduced CAD risks in East Asians (for rs187238: allelic OR = 0.72, homozygous OR = 0.33, heterozygous OR = 0.73, dominant OR = 0.71; for rs1946518: allelic OR = 0.62, homozygous OR = 0.38, heterozygous OR = 0.49, dominant OR = 0.45). IL-18-rs187238 also demonstrated protective effects in Middle Eastern populations (allelic OR = 0.76, homozygous OR = 0.63, heterozygous OR = 0.72, dominant OR = 0.71). No significant associations were observed in South Asians or Caucasians for these IL-18 SNPs. Consistent with the overall analysis results, subgroups analyses further highlighted a significant association between IL-8-rs4073 and increased risk of acute coronary syndrome (heterozygous OR = 0.72). IL-18-rs187238 was significantly associated with decreased risks of myocardial infarction (MI) (allelic OR = 0.81, homozygous OR = 0.55, dominant OR = 0.80) and multiple vessel stenosis (allelic OR = 0.54, heterozygous OR = 0.45, dominant OR = 0.45). Similarly, IL-18-rs1946518 was significantly associated with reduced MI risk (allelic OR = 0.75, heterozygous OR = 0.68). These findings support the role of cytokine gene IL-8 and IL-18 variants as predisposing factors for the development and progression of CAD. Full article

Growth differentiation factor 15 (GDF15) is a stress-response cytokine related to a wide variety of metabolic diseases. However, the impact of GDF15-specific genetic variants on the abovementioned conditions is poorly known. The aim of this study was to assess the impact of selected GDF15 single-nucleotide polymorphisms (SNPs) on metabolic disturbances and subclinical atherosclerosis. A cross-sectional study involving 153 participants of a metabolic patient-based cohort was performed. Three selected SNPs (rs888663, rs1054564 and rs1059369) in a locus on chromosome 19 including the GDF15 gene were genotyped by Polymerase Chain Reaction (PCR), and its relationship with the serum GDF15 levels, health status and clinical variables were analyzed. Of the three SNPs analyzed, only rs1054564 showed different distributions between the healthy volunteers and patients suffering lipid alterations and associated disorders. Accordingly, just the rs1054564 variant carriers showed a significant increase in GDF15 serum levels compared to the wild-type carriers. The group of variant carriers showed a higher frequency of individuals with diabetes, compared to the wild-type carrier group, without showing differences in other metabolic conditions. Additionally, the frequency of individuals with atherosclerotic carotid plaque was higher in the rs1054564 variant carriers than in the wild-type carriers. Logistic regression models identified that the presence of the rs1054564 variant carriers increase the likelihood for both diabetes and carotid plaque independently of confounding factors. Overall, the findings of this study identify the rs1054564 variant as a potential indicator for the likelihood of diabetes and subclinical atherosclerosis. Full article

Background: The genetic background of Toll-like receptor 4 (TLR4) proved to be important in the induction of immune protection against Bordetella pertussis infection in humans. Currently, the evaluation of the acellular pertussis (aP) vaccine depends largely on using different mouse strains, while the TLR4 genotype of different mouse strains in response to pertussis toxin (PT) is not carefully determined. The current study was designed to determine the differences in TLR4 genotype and TLR4 pathway-related cytokines in response to PT stimulation among mouse strains of ICR, NIH, and BALB/c. Method: We first determined the single-nucleotide polymorphisms (SNPs) in the TLR4 gene by using first-generation sequencing. Then, the cellular response, including the TLR4 mRNA expression and TLR4 signaling-related cytokines, of immune cells from different mouse strains after PT stimulation was determined. Result: Three missense mutation sites (rs13489092, rs13489093, rs13489097) of the TLR4 gene were found. ICR mice were homozygous without mutation, NIH mice were partially heterozygous, and BALB/c mice were homozygous with a missense mutation. The expression of TLR4 was repressed while the downstream cytokines were upregulated after PT stimulation differently among mouse strains. The IFN-β cytokine of the TRIF pathway was significantly increased in ICR mice (p < 0.05). The IL-6 cytokine of the MyD88-dependent pathway was significantly increased in BALB/c mice (p < 0.05). The identified SNPs of the TLR4 gene in different mouse strains might account for the differences in cytokines levels determined after PT stimulation. Conclusions: Our studies might provide useful referees to reduce the mouse-derived difference in the determination of vaccine titer and increase the comparability of the vaccine from different origins, as different mouse strains were used for vaccine development in different countries. Full article

Cardiovascular disease (CVD) may be inherited, as recently shown with the identification of single nucleotide polymorphisms (SNPs or “snips”) on a 250 kb DNA fragment that encodes 92 proteins associated with CVD. CVD is also triggered by microbial dysbiosis, microbial metabolites, metabolic disorders, and inflammatory intestinal epithelial cells (IECs). The epithelial cellular adhesion molecule (Ep-CAM) and trefoil factor 3 (TFF3) peptide keeps the gut wall intact and healthy. Variations in Ep-CAM levels are directly linked to changes in the gut microbiome. Leptin, plasminogen activator inhibitor 1 (PAI1), and alpha-1 acid glycoprotein 1 (AGP1) are associated with obesity and may be used as biomarkers. Although contactin 1 (CNTN1) is also associated with obesity and adiposity, it regulates the bacterial metabolism of tryptophan (Trp) and thus appetite. A decrease in CNTN1 may serve as an early warning of CVD. Short-chain fatty acids (SCFAs) produced by gut microbiota inhibit pro-inflammatory cytokines and damage vascular integrity. Trimethylamine N-oxide (TMAO), produced by gut microbiota, activates inflammatory Nod-like receptors (NLRs) such as Nod-like receptor protein 3 (NLRP3), which increase platelet formation. Mutations in the elastin gene (ELN) cause supra valvular aortic stenosis (SVAS), defined as the thickening of the arterial wall. Many of the genes expressed by human cells are regulated by gut microbiota. The identification of new molecular markers is crucial for the prevention of CVD and the development of new therapeutic strategies. This review summarizes the causes of CVD and identifies possible CVD markers. Full article

Background: Periodontitis is a complex disease, and bacterial factors play a crucial role in its initiation. The contributions of genetic and epigenetic factors to the pathogenesis of periodontal disease are increasingly recognized. Single-nucleotide polymorphisms (SNPs) in various molecules, including cytokines, are of particular interest due to their established involvement in numerous diseases. This study investigates the influence of SNPs in the IL-10 gene at positions −592 (rs1800872) C>A and −1082 (rs1800896) T>C (also referred to as 1082A>G) on the severity of periodontitis in a cohort of Bulgarian patients. Methods: In the recent study, both clinical and paraclinical methodologies were employed to comprehensively assess the periodontal status of the participants. The genotypic characterization of IL-10 polymorphisms was performed by PCR RFLP analysis. Statistical analyses, including principal component analysis (PCA), were executed utilizing IBM SPSS Statistics Version 21. Results: We have established a statistically significant association between the presence of at least one A-allele in the patients’ genotype and the incidence of severe periodontitis (p = 0.047). Conclusions: IL-10 single-nucleotide polymorphisms (SNPs) could be effectively considered as biomarkers for the severity of periodontitis. Full article

(1) Background: Osteoarthritis (OA) is a heterogeneous disorder, and subgroup classification of OA remains elusive. The aim of our study was to identify endotypes of hip OA and investigate the altered pathways in the different endotypes. (2) Methods: Metabolomic profiling and genome-wide genotyping were performed on fasting blood. Transcriptomic profiling was performed on RNA extracted from cartilage samples. Machine learning methods were used to identify endotypes of hip OA. Pathway analysis was used to identify the altered pathways between hip endotypes and controls. GWAS was performed on each of the identified metabolites. Transcriptomic data was used to examine the expression levels of identified genes in cartilage. (3) Results: 180 hip OA patients and 120 OA-free controls were classified into three clusters based on metabolomic data. The combination of arginine, ornithine, and the average value of 7 lysophosphatidylcholines had an area under the curve (AUC) of 0.97 (95% CI: 0.96–0.99) to discriminate hip OA from controls, and the combination of γ-aminobutyric acid, spermine, aconitic acid, and succinic acid had an AUC of 0.96 (95% CI: 0.94–0.99) to distinguish two hip OA endotypes. GWAS identified 236 SNPs to be associated with identified metabolites at GWAS significance level. Pro-inflammatory cytokine levels were significantly different between two endotypes (all p < 0.05). (4) Conclusions: Hip OA could be classified into two distinct molecular endotypes. The primary differences between the two endotypes involve changes in pro-inflammatory factors and energy metabolism. Full article

(1) Multiple sclerosis (MS) is identified by a complex interaction between central inflammation and neurodegeneration. Genetic individual variability could play a significative role in clinical presentation. The interleukin-5 (IL-5) rs2069812 single-nucleotide polymorphism (SNP) seems to define the clinical course of Th2 autoimmune diseases, while its role in MS has never been investigated. (2) In a group of 230 patients diagnosed with relapsing–remitting MS (RR-MS) or progressive MS (P-MS) and controls (IC), rs2069812 polymorphism, cerebrospinal fluid (CSF) levels of inflammatory mediators, and clinical and demographic characteristics were determined. In RR-MS patients, No Evidence of Disease Activity (NEDA-3) at three years of follow-up was detected. (3) We identified higher levels of proinflammatory cytokines, particularly IL-2 (median [IQR], RR-MS = 0.2 [0–0.7]; P-MS = 0.1 [0–1.6]; IC = 0.1 [0.0–0.1]; p < 0.005), IL-6 (RR-MS = 0.9 [0.3–2.3]; P-MS = 0.8 [0.1–2.7]; IC = 0.1 [0.0–0.5]; p < 0.005), IL-12 (RR-MS = 0.5 [0–1.1]; P-MS = 0.5 [0–1.1]; IC = 0.0 [0.0–0.3]; p < 0.005), and GM-CSF (RR-MS = 15.6 [4.8–26.4]; P-MS = 14 [3.3–29.7]; IC = 8.9 [4.7–11.7]; p < 0.005) in MS patients compared with IC. Conversely, anti-inflammatory cytokines, specifically IL-5 (RR-MS = 0.65 [0–2.4]; P-MS = 0.1 [0–0.8]; IC = 1.7 [0.6–2.8]; p < 0.005) and IL-1ra (RR-MS = 14.7 [4.9–26.4]; P-MS = 13.1 [4.7–22.2]; IC = 27.8 [17.7–37.6]; p < 0.005) were higher in controls. According to rs2069812, in MS patients, the T-allele was associated with higher concentrations of proinflammatory mediators (IL-2, CT/TT = 0.2 [0.0–2.0]; CC = 0.1 [0.0–0.4], p = 0.015; IL-6, CT/TT = 1.2 [0.4–3.2] vs. CC = 0.7 [0.1–1.7], p = 0.007; IL-15, CT/TT = 0.1 [0.0–9.5] vs. CC = 0.0 [0.0–0.1], p = 0.019; and GM-CSF, CT/TT = 0.1 [0.0–0.6] vs. CC = 0.05 [0.0–0.1], p < 0.001), and CC was associated with anti-inflammatory mediators (IL-5, CT/TT = 0.03 [0.0–1.9] vs. CC = 1.28 [0.0–2.7], p = 0.001; IL-1ra, CT/TT = 12.1 [4.1–25.9] vs. CC = 18.1 [12.1–26.9], p = 0.006). We found the same differences in RR-MS patients (IL-2, T-allele median [IQR] = 0.3 [0.0–2.0] vs. C-allele, median [IQR] = 0.04 [0.0–0.3]; p = 0.005; IL-6, T-allele, median [IQR] = 1.3 [0.4–3.3] vs. C-allele, median [IQR] = 0.6 [0.03–1.5]; p = 0.001; IL-15, T-allele, median [IQR] = 0.1 [0.0–9.5] vs. C-allele, median [IQR] = 0.0 [0.0–0.1]; p = 0.008; GM-CSF, T-allele, median [IQR] = 0.1 [0.0–97.9] vs. C-allele, median [IQR] = 0.0 [0.0–0.001]; p < 0.001; IL-5, T-allele, median [IQR] = 0.02 [0.0–2.2] vs. C-allele, median [IQR] = 1.5 [0.0–2.9]; p = 0.016; and IL-1ra, T-allele, median [IQR] = 12.1 [4.3–26.4] vs. C-allele, median [IQR] = 18.5 [12.7–28.3]; p = 0.006) but not in P-MS, except for IL-5 (T-allele, median [IQR] = 0.1 [0–0.23] vs. C-allele, median [IQR] = 0.6 [0.0–2.5]; p = 0.022). Finally, we identified an association between CC in RR-MS patients and NEDA-3 after three years of follow-up (p = 0.007). (4) We describe, for the first time, the role of an SNP of the IL-5 gene in regulating central neuroinflammation and influencing clinical course in MS patients. Full article