Causal effects of inflammatory protein biomarkers on inflammatory diseases.
Ontology highlight
ABSTRACT:
SUBMITTER: Ek WE
PROVIDER: S-EPMC8654293 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundThe causal relationship between inflammatory cytokines and cardiovascular diseases (CVDs) has not been fully elucidated. Exploring this relationship between circulating inflammatory cytokines and CVDs is crucial for early clinical diagnosis and effective treatment.Methods and resultsThis study investigated the causal relationships between 41 inflammatory cytokines and six CVDs: heart failure (HF), myocardial infarction (MI), unstable angina pectoris (UAP), stable angina pectoris (SAP), valvular heart disease (VHD), and aortic aneurysm (AA), using the Mendelian Randomization (MR) method. The primary analysis employed the inverse-variance weighted (IVW) method within MR. Heterogeneity and pleiotropy were assessed through MR-Egger regression and the Q statistic. Strong evidence supported the effect of macrophage inflammatory protein-1β (MIP-1β) on MI (OR = 1.062, P < 0.001, FDR <0.001). Suggestive evidence showed that the Beta nerve growth factor increased the risk of MI (OR = 1.145, P = 0.025), but the stem cell factor (SCF) demonstrated a potential protective effect against MI (OR = 0.910, P = 0.04). SCF and hepatocyte growth factor (HGF) exhibited potential protective effects against SAP. No inflammatory cytokine was associated with UAP. Monocyte chemotactic protein-1 was linked to an increased risk of VHD (OR = 1.056, P = 0.049). Higher levels of interleukin-13 (IL-13), interferon gamma-induced protein 10 (IP-10), and growth-regulated oncogene-alpha were associated with increased susceptibility to HF. Elevated basic fibroblast growth factor (bFGF) levels exhibited protective effects against AA (OR = 0.751, P = 0.038). Reverse MR analyses revealed that AA significantly decreased circulating TNF-related apoptosis-inducing ligand (TRAIL) levels (OR = 0.907, P < 0.001, FDR = 0.01). MI significantly increased circulating IL-12-p70 levels (OR = 1.146, P < 0.001, FDR = 0.014). Suggestive evidence indicated the Causal effects of six CVDs on 17 circulating inflammatory cytokines.ConclusionsThis study clarified the causal relationships between specific inflammatory cytokines and six CVDs, providing novel insights and evidence into the genetic involvement of inflammatory cytokines in CVDs. These inflammatory cytokines may be potential biomarkers for early disease diagnosis and treatment evaluation.
| S-EPMC11334864 | biostudies-literature
Project description:BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases.MethodsSeven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness.ResultsPlasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock.ConclusionOur findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.
| S-EPMC11003410 | biostudies-literature
Project description:BackgroundThere is an incompletely understood increased risk for cardiovascular disease (CVD) among people with HIV (PWH). We investigated if a collection of biomarkers were associated with CVD among PWH. Mendelian randomization (MR) was used to identify potentially causal associations.MethodsData from follow-up in 4 large trials among PWH were used to identify 131 incident CVD cases and they were matched to 259 participants without incident CVD (controls). Tests of associations between 460 baseline protein levels and case status were conducted.ResultsUnivariate analysis found CLEC6A, HGF, IL-6, IL-10RB, and IGFBP7 as being associated with case status and a multivariate model identified 3 of these: CLEC6A (odds ratio [OR] = 1.48, P = .037), HGF (OR = 1.83, P = .012), and IL-6 (OR = 1.45, P = .016). MR methods identified 5 significantly associated proteins: AXL, CHI3L1, GAS6, IL-6RA, and SCGB3A2.ConclusionsThese results implicate inflammatory and fibrotic processes as contributing to CVD. While some of these biomarkers are well established in the general population and in PWH (IL-6 and its receptor), some are novel to PWH (HGF, AXL, and GAS6) and some are novel overall (CLEC6A). Further investigation into the uniqueness of these biomarkers in PWH and the role of these biomarkers as targets among PWH is warranted.
| S-EPMC10319949 | biostudies-literature
Project description:Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system. Only a few biomarkers are available in MS clinical practice, such as cerebrospinal fluid oligoclonal bands and immunoglobulin index, serum anti-aquaporin 4 antibodies, and serum anti-John Cunningham virus antibodies. Thus, there is a significant unmet need for biomarkers to assess prognosis, response to therapy, or potential treatment complications. Here we describe emerging biomarkers that are in development, focusing on those from peripheral blood. There are several limitations in the process of discovery and validation of a good biomarker, such as the pathophysiological complexity of MS and the technical difficulties in globally standardizing methods for sampling, processing, and conserving biological specimens. In spite of these limitations, ongoing international collaborations allow the exploration of many interesting molecules and markers to validate diagnostic, prognostic, and therapeutic-response biomarkers.
| S-EPMC5233628 | biostudies-literature
Project description:The inflammatory bowel diseases (IBD), which include mainly Crohn's disease (CD) and ulcerative colitis (UC), are common chronic inflammatory conditions of the digestive system. The diagnosis of IBD relies on the use of a combination of factors including symptoms, endoscopy and levels of serum proteins such as C-reactive protein (CRP) or faecal calprotectin. Currently there is no single reliable biomarker to determine IBD. Galectins are a family of galactoside-binding proteins that are commonly altered in the circulation of disease conditions such as cancer and inflammation. This study investigated serum galectin levels as possible biomarkers in determining IBD and IBD disease activity. Levels of galectins-1, -2, -3, -4, -7 and -8 were analysed in 208 samples from ambulant IBD patients (97 CD, 71 UC) patients and 40 from healthy people. Disease activity was assessed using Harvey-Bradshaw Index for CD and simple clinical colitis activity index for UC. The relationship of each galectin in determining IBD and IBD disease activity were analysed and compared with current IBD biomarker CRP. It was found that serum level of galectin-1 and -3, but not galectins-2, -4, -7 and -8, were significantly higher in IBD patients than in healthy people. At cut-off of 4.1ng/ml, galectin-1 differentiated IBD from healthy controls with 71% sensitivity and 87% specificity. At cut-off of 38.5ng/ml, galectin-3 separated IBD from healthy controls with 53% sensitivity and 87% specificity. None of the galectins however were able to distinguish active disease from remission in UC or CD. Thus, levels of galectins-1 and -3 are significantly elevated in both UC and CD patients compared to healthy people. Although the increased galectin levels are not able to separate active and inactive UC and CD, they may have the potential to be developed as useful biomarkers for IBD diagnosis either alone or in combination with other biomarkers.
| S-EPMC6957193 | biostudies-literature
Project description:Recent advances in data analysis methods based on principles of Mendelian Randomisation, such as Egger regression and the weighted median estimator, add to the researcher's ability to infer cause-effect links from observational data. Now is the time to gauge the potential of these methods within specific areas of biomedical research. In this paper, we choose a study in metabolomics as an illustrative testbed. We apply Mendelian Randomisation methods in the analysis of data from the DILGOM (Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome) study, in the context of an effort to identify molecular pathways of cardiovascular disease. In particular, our illustrative analysis addresses the question whether body mass, as measured by body mass index (BMI), exerts a causal effect on the concentrations of a collection of 137 cardiometabolic markers with different degrees of atherogenic power, such as the (highly atherogenic) lipoprotein metabolites with very low density (VLDLs) and the (protective) high density lipoprotein metabolites.We found strongest evidence of a positive BMI effect (that is, evidence that an increase in BMI causes an increase in the metabolite concentration) on those metabolites known to represent strong risk factors for coronary artery disease, such as the VLDLs, and evidence of a negative effect on protective biomarkers.The methods discussed represent a useful scientific tool, although they assume the validity of conditions that are (at best) only partially verifiable. This paper provides a rigorous account of such conditions. The results of our analysis provide a proof-of-concept illustration of the potential usefulness of Mendelian Randomisation in genomic biobank studies aiming to dissect the molecular causes of disease, and to identify candidate pharmacological targets.
| S-EPMC6069804 | biostudies-other
Project description:There are inconsistent findings in the literature about the directionality and magnitude of the association between inflammation and depressive symptoms. This analysis separates predictors into between-person and within-person components to gain greater clarity about this relationship. Blood samples were collected and depressive symptoms assessed in 140 adolescents (54% female, 59% Black, Mage = 16.1 years) with at least three blood draws and a total of 394 follow-up observations. Multi-level modeling indicated that the within-person effect of tumor necrosis factor alpha (TNF-α) predicted change in total depressive symptoms, suggesting a potential causal relationship. There were no significant within-person effects of total depressive symptoms on change in biomarkers. Exploratory analyses examined associations between inflammatory biomarkers and subsets of depressive symptoms. These findings inform modeling decisions that may explain inconsistencies in the extant literature as well as suggest potential causal relationships between certain proteins with significant within-person effects on depressive symptoms, and vice-versa.
| S-EPMC7386405 | biostudies-literature
Project description:ObjectivesTo investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout.MethodsThe random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs).ResultsThere was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94-1.10, p = 0.74; OR = 1.00, 95% CI: 0.999-1.000, p = 0.50; OR = 1.00, 95% CI: 1.000-1.001, p = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96-1.07, p = 0.66; OR = 1.00, 95% CI: 1.00-1.00, p = 0.68; OR = 1.00, 95% CI: 1.00-1.00, p = 0.20].ConclusionOur study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.
| S-EPMC11004292 | biostudies-literature
Project description:Many studies have demonstrated the linkage between the IBD3 region (6p21.1-23), an area which encompasses the famous human leukocyte antigen (HLA) complex, and Crohn's disease (CD) or ulcerative colitis (UC). IBD3 is the only region that meets genome-wide significance, and provides stronger evidence of the linkage than 16p13.1-16q12.2 (IBD1), the locus that contains the susceptibility gene CARD15. However, despite these findings, IBD3 susceptibility genes remain elusive and unclear due to the strong linkage disequilibrium, extensive polymorphism, and high gene density that characterize this area and also due to varying allele frequencies in populations around the world. This area presents an extremely high abundance of genes, including the classical and non-classical major histocompatibility complex (MHC) class I and II genes, and other genes, namely MHC class III genes tumor necrosis factor (TNF)-? and -?, and Hsp, whose proteins play key functions in immunological processes. To date, it is not clear which genes within the MHC family contribute to the IBD pathogenesis, although certain HLA alleles have been associated with IBD. Recent insights into the biological function of other genes encoded within the IBD3 region, such as the MHC class I chain-related (MIC) genes, have led investigators to a more comprehensive exploration of this region. MHC class I chain-related molecule A (MICA) is highly polymorphic and interacts with NKG2D, its receptor on the surface of NK, T?? and T CD8(+) cells. Increased expression of MICA in intestinal epithelial cells and increased expression of NKG2D in CD4(+) T cells (lamina propria) in patients with CD have also been reported. MICA alleles have also been associated with IBD, and a variation at amino acid position 129 of the ?2-heavy chain domain seems to categorize MICA alleles into strong and weak binders of NKG2D receptor, thereby influencing the effector cells' function. In this regard, a relevant role of MICA-129-Val/Met single nucleotide polymorphism has recently been implicated in the pathogenesis of IBD. TNF-? and -? also play an important role in inflammatory response. In fact, IBD is commonly treated with TNF-? inhibitors. Additionally, polymorphisms of TNF-? gene are known to affect the gene expression level and particular TNF-? genotypes may influence the response of IBD patients treated with TNF-? inhibitors.
| S-EPMC4223237 | biostudies-literature
Project description:Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology which mostly involves the intestine and requires a personalized approach for treatment. IBD represents a heterogeneous group of patients with inherently variable disease courses. Hence, the heterogeneity of patient populations may delay the diagnosis, clinical practice and initiation of appropriate treatment. Use of biomarkers for diagnosis and management of IBD is still necessary. Descriptions of the immunological pathway abnormalities in IBD improve assessment to identify the patient's disease status, and relative risk of progression to complicated disease behaviors, and this information may ultimately influence therapeutic decisions. In this study, we try to explain the role of biomarkers in early diagnosis, estimating prognosis, and target agents for correct managements of IBD's patients. This information might be important to provide insight into emerging panels of multiple IBD biomarkers and highlighting the essential role of personalizes panel for each patient.
| S-EPMC5660264 | biostudies-literature