Longitudinal association of the anti-inflammatory serum marker GDF-15 with serum IgA and IgG in apparently healthy children.
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ABSTRACT:
SUBMITTER: Carreras-Badosa G
PROVIDER: S-EPMC8440501 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Anti-glycan antibodies are an abundant subpopulation of serum antibodies with critical functions in many immune processes. Changes in the levels of these antibodies can occur with the onset of disease, exposure to pathogens, or vaccination. As a result, there has been significant interest in exploiting anti-glycan antibodies as biomarkers for many diseases. Serum contains a mixture of anti-glycan antibodies that can recognize the same antigen, and competition for binding can potentially influence the detection of antibody subpopulations that are more relevant to disease processes. The most abundant antibody isotypes in serum are IgG, IgM, and IgA, but little is known regarding how these different isotypes compete for the same glycan antigen. In this study, we developed a multiplexed glycan microarray assay and applied it to evaluate how different isotypes of anti-glycan antibodies (IgA, IgG, and IgM) compete for printed glycan antigens. While IgG and IgA antibodies typically outcompete IgM for peptide or protein antigens, we found that IgM outcompete IgG and IgA for many glycan antigens. To illustrate the importance of this effect, we provide evidence that IgM competition can account for the unexpected observation that IgG of certain antigen specificities appear to be preferentially transported from mothers to fetuses. We demonstrate that IgM in maternal sera compete with IgG resulting in lower than expected IgG signals. Since cord blood contains very low levels of IgM, competition only affects maternal IgG signals, making it appear as though certain IgG antibodies are higher in cord blood than matched maternal blood. Taken together, the results highlight the importance of competition for studies involving anti-glycan antibodies.
| S-EPMC4373866 | biostudies-literature
Project description:PurposeTo date, the relationship between Growth Differentiation Factor 15 (GDF-15) gene polymorphism and the risk of type 2 diabetes mellitus (T2DM) has not been clarified. Our study aims to explore the association between serum GDF-15 levels and related gene polymorphism with the risk of T2DM in a Chinese rural Yao population.MethodsThis was a 1:1 case-control study with 179 T2DM patients and 179 age- and sex-matched control participants. Serum GDF-15 levels were measured by enzyme-linked immunosorbent assay, and polymorphisms (rs1059519, rs1059369, rs1804826 and rs1054564) were genotyped by MassArray mass spectrometry.ResultsSerum GDF-15 (sGDF-15) levels were higher in patients with T2DM and glycosylated hemoglobin (HbA1c) ≥ 6.5 % compared to that in controls (p < 0.001). The area under the curve (AUC) corresponding to sGDF-15 levels was 0.626. Serum GDF-15 was positively correlated with fasting plasma glucose (FPG) (rs = 0.150, p < 0.001) and HbA1c (rs = 0.160, p < 0.001). The frequency of GDF-15 gene rs1054564 GC + CC genotype was significantly associated with increased risk of T2DM compared to GG genotype (OR = 1.724, 95CI: 1.046-2.841, p = 0.033). Frequencies of rs1804826 T allele (β additive = 113.318, p = 0.026) and rs1054564 C allele (β additive = 247.282, p = 0.001, β dominant = 286.109, p = 0.001) was significantly correlated with higher sGDF-15. The rs1059519 C allele was negatively correlated with FPG (β recessive = -0.607, p = 0.047) and HbA1c (β recessive = -0.456, p = 0.020).ConclusionSerum GDF-15 levels were positively correlated with FPG and HbA1c. The GDF-15 rs1054564 GC + CC genotype was associated with a significantly higher T2DM risk. The rs1059519 C allele was negatively correlated with FPG and HbA1c.
| S-EPMC11234026 | biostudies-literature
Project description:BackgroundAccumulating evidence suggests that chronic prostatic inflammation may lead to prostate cancer development. Growth differentiation factor-15 (GDF-15) is highly expressed in the prostate and has been associated with inflammation and tumorigenesis.MethodsTo examine the relationship between GDF-15 and prostatic inflammation, GDF-15 expression was measured by immunohistochemical (IHC) staining in human prostatectomy specimens containing inflammation. The relationship between GDF-15 and specific inflammatory cells was determined using non-biased computer image analysis. To provide insight into a potential suppressive role for GDF-15 in inflammation, activation of inflammatory mediator nuclear factor of kappa B (NFκB) was measured in PC3 cells.ResultsGDF-15 expression in luminal epithelial cells was decreased with increasing inflammation severity, suggesting an inverse association between GDF-15 and inflammation. Quantification of IHC staining by image analysis for GDF-15 and inflammatory cell markers revealed an inverse correlation between GDF-15 and CD3+, CD4+, CD8+, CD68+, and inos+ leukocytes. GDF-15 suppressed NFκB activity in luciferase reporter assays. Expression of the NFκB target, interleukin 8 (IL-8), was downregulated by GDF-15.ConclusionsThe inverse relationship between GDF-15 and inflammation demonstrates a novel expression pattern for GDF-15 in the human prostate and suppression of NFκB activity may shed light on a potential mechanism for this inverse correlation.
| S-EPMC4682671 | biostudies-literature
Project description:ObjectiveChronic low-grade inflammation and adipokines dysregulation are linked to mechanisms underscoring the pathogenesis of obesity-related metabolic disorders. Little is known about roles of these cytokines on the association between snoring and metabolic syndrome (MetS). We aimed to investigate whether a cluster of cytokines are related to snoring frequency and its association with MetS in apparently healthy Chinese.MethodsCurrent analyses used a population-based sample including 1059 Shanghai residents aged 35-54 years. Self-reported snoring frequency was classified as never, occasionally and regularly. Fasting plasma glucose, lipid profile, insulin, C-reactive protein, interleukin-6, interleukin-18, lipopolysaccharide binding protein, high-molecular-weight adiponectin and leptin were measured. MetS was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans.ResultsOverweight/obese subjects had significantly higher prevalence of regular snorers than their normal-weight counterparts (34.8% vs. 11.5%, P<0.001). Regular snoring was associated with unfavorable profile of inflammatory markers and adipokines. However, those associations were abolished after adjustment for body mass index (BMI) or waist circumference. The MetS risk (multivariate-adjusted odds ratio 5.41, 95% confidence interval 3.72-7.88) was substantially higher in regular snorers compared with non-snorers. Controlling for BMI remarkably attenuated the association (2.03, 1.26-3.26), while adjusting for inflammatory markers and adipokines showed little effects.ConclusionFrequent snoring was associated with an elevated MetS risk independent of lifestyle factors, adiposity, inflammatory markers and adipokines in apparently healthy Chinese. Whether snoring pattern is an economic and no-invasive indicator for screening high-risk persons needs to be addressed prospectively.
| S-EPMC3217970 | biostudies-literature
Project description:BackgroundInflammatory bowel disease (IBD) is associated with a defective intestinal barrier and enhanced adaptive immune responses against commensal microbiota. Immune responses against food antigens in IBD patients remain poorly defined.MethodsIgG and IgA specific for food and microfloral antigens (wheat and milk extracts; purified ovalbumin; Escherichia coli and Bacteroides fragilis lysates; mannan from Saccharomyces cerevisiae) were analyzed by ELISA in the serum and feces of patients with Crohn's disease (CD; n?=?52 for serum and n?=?20 for feces), ulcerative colitis (UC; n?=?29; n?=?17), acute gastroenteritis/colitis (AGE; n?=?12; n?=?9) as well as non-inflammatory controls (n?=?61; n?=?39).ResultsSerum anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-B. fragilis IgG and IgA levels were increased in CD patients whereas antibody (Ab) levels against E. coli and food antigens were not significantly different within the patient groups and controls. Subgroup analysis revealed that CD patients with severe diseases defined by stricturing and penetrating lesions have slightly higher anti-food and anti-microbial IgA levels whereas CD and UC patients with arthropathy have decreased anti-food IgG levels. Treatment with anti-TNF-? Abs in CD patients was associated with significantly decreased ASCA IgG and IgA and anti-E. coli IgG. In the feces specific IgG levels against all antigens were higher in CD and AGE patients while specific IgA levels were higher in non-IBD patients. Anti-food IgG and IgA levels did not correlate with food intolerance.SummaryIn contrast to anti-microbial Abs, we found only minor changes in serum anti-food Ab levels in specific subgroups of IBD patients. Fecal Ab levels towards microbial and food antigens show distinct patterns in controls, CD and UC patients.
| S-EPMC4162554 | biostudies-literature
Project description:PurposeSarcopenia is closely associated with postoperative prognosis in patients undergoing cardiovascular surgery. Growth differentiation factor (GDF)-15 is involved in the pathogenesis of cardiovascular disease. We examined the relationship between the serum GDF-15 concentration and muscle function in patients receiving aortic valve replacement and healthy elderly subjects.MethodsForty-three female patients undergoing aortic valve surgery (79.9 ± 6.4 years; transcatheter aortic valve replacement [TAVR] n = 19, conventional surgical aortic valve replacement [SAVR] n = 24) and 64 healthy elderly female subjects (75.9 ± 6.1 years) were included. Walking speed, grip strength, and skeletal muscle mass index (SMI) by a multifrequency bioelectrical impedance analyzer were measured to determine the presence of sarcopenia. Preoperative serum GDF-15 concentration was measured by enzyme-linked immunosorbent assay.ResultsThe GDF-15 level was higher in patients receiving aortic valve replacement than in healthy elderly subjects (aortic valve replacement: 1624 ± 1186 pg/mL vs. healthy: 955 ± 368 pg/mL, p < 0.001). Multivariate linear regression analysis showed that the serum GDF-15 level determined grip strength independently of the high-sensitivity C-reactive protein level and eGFR, even after adjusting for age (β = -0.318, p = 0.025). Sarcopenia was found in 12.5% of healthy elderly subjects, 83.3% of patients with TAVR, and 64.3% of patients with SAVR. The GDF-15 concentration that defined sarcopenia was 1109 pg/mL in subjects including patients receiving aortic valve replacement.ConclusionsThe preoperative serum GDF-15 concentration, which was higher in female patients receiving aortic valve replacement than in healthy elderly subjects, may be a serum marker of sarcopenia.
| S-EPMC9043358 | biostudies-literature
Project description:IgA nephropathy is an autoimmune disease characterized by IgA1-containing glomerular immune deposits. We previously proposed a multi-hit pathogenesis model in which patients with IgA nephropathy have elevated levels of circulatory IgA1 with some O-glycans deficient in galactose (Gd-IgA1, autoantigen). Gd-IgA1 is recognized by anti-glycan IgG and/or IgA autoantibodies, resulting in formation of pathogenic immune complexes. Some of these immune complexes deposit in the kidney, activate mesangial cells, and incite glomerular injury leading to clinical presentation of IgA nephropathy. Several studies have demonstrated that elevated circulatory levels of either Gd-IgA1 or the corresponding autoantibodies predict progressive loss of renal clearance function. In this study we assessed a possible association between serum levels of Gd-IgA1 and IgG or IgA autoantibodies specific for Gd-IgA1 in serum samples from 135 patients with biopsy-proven IgA nephropathy, 76 patients with other renal diseases, and 106 healthy controls. Our analyses revealed a correlation between the concentrations of the autoantigen and the corresponding IgG autoantibodies in sera of patients with IgA nephropathy, but not of disease or healthy controls. Moreover, our data suggest that IgG is the predominant isotype of Gd-IgA1-specific autoantibodies in IgA nephropathy. This work highlights the importance of both initial hits in the pathogenesis of IgA nephropathy.
| S-EPMC5764330 | biostudies-literature
Project description:BackgroundIn patients with cancer, hepatocyte growth factor (HGF) is elevated and is a predictor of prognosis. We investigated whether serum HGF was a predictive marker for cancer death in a population of community-dwelling Japanese.MethodsWe studied 1492 apparently healthy Japanese adults who underwent health examinations in 1999. Those who reported a history of liver disease or malignancy on a baseline questionnaire were excluded, and plasma HGF was measured in the remaining 1470 participants, who were followed periodically for 10 years. Multivariate proportional hazards regression was used to estimate cancer mortality.ResultsA total of 169 participants died during follow-up (61 from cancer, 32 from cerebrocardiovascular disease, and 76 from other diseases). Mean HGF at baseline was significantly higher among decedents than among survivors (0.26 ± 0.11 vs 0.23 ± 0.09 ng/ml, respectively; P < 0.01). The Cox proportional hazards model showed that age, systolic blood pressure, HGF (hazard ratio, 1.27; 95% CI, 1.06-1.52; P = 0.009), albumin level, smoking status, and creatinine were independent predictors of all-cause death. Age, HGF (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = 0.02), and total cholesterol were independent predictive markers for cancer death.ConclusionsSerum HGF was a predictor of cancer death in an apparently healthy population of community-dwelling Japanese.
| S-EPMC3798633 | biostudies-literature
Project description:The development of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). SLE serum can induce monocyte differentiation into dendritic cells (DCs) in a type I IFN-dependent manner. Such SLE-DCs activate T cells, but whether they promote B cell responses is not known. In this study, we demonstrate that SLE-DCs can efficiently stimulate naive and memory B cells to differentiate into IgG- and IgA-plasmablasts (PBs) resembling those found in the blood of SLE patients. SLE-DC-mediated IgG-PB differentiation is dependent on B cell-activating factor (BAFF) and IL-10, whereas IgA-PB differentiation is dependent on a proliferation-inducing ligand (APRIL). Importantly, SLE-DCs express CD138 and trans-present CD138-bound APRIL to B cells, leading to the induction of IgA switching and PB differentiation in an IFN-?-independent manner. We further found that this mechanism of providing B cell help is relevant in vivo, as CD138-bound APRIL is expressed on blood monocytes from active SLE patients. Collectively, our study suggests that a direct myeloid DC-B cell interplay might contribute to the pathogenesis of SLE.
| S-EPMC3405503 | biostudies-other
Project description:GDF-15 (growth differentiation factor 15) acts both as a stress-induced cytokine with diverse actions at different body sites and as a cell-autonomous regulator linked to cellular senescence and apoptosis. For multiple reasons, this divergent transforming growth factor-β molecular superfamily member should be better known to pulmonary researchers and clinicians. In ambulatory individuals, GDF-15 concentrations in peripheral blood are an established predictive biomarker of all-cause mortality and of adverse cardiovascular events. Concentrations upon admission of critically ill patients (without or with sepsis) correlate with organ dysfunction and independently predict short- and long-term mortality risk. GDF-15 is a major downstream mediator of p53 activation, but it can also be induced independently of p53, notably by nonsteroidal antiinflammatory agents. GDF-15 blood concentrations are markedly elevated in adults and children with pulmonary hypertension. Concentrations are also increased in chronic obstructive pulmonary disease, in which they contribute to mucus hypersecretion, airway epithelial cell senescence, and impaired antiviral defenses, which together with murine data support a role for GDF-15 in chronic obstructive pulmonary disease pathogenesis and progression. This review summarizes biological and clinical data on GDF-15 relevant to pulmonary and critical care medicine. We highlight the recent discovery of a central nervous system receptor for GDF-15, GFRAL (glial cell line-derived neurotrophic factor family receptor-α-like), an important advance with potential for novel treatments for obesity and cachexia. We also describe limitations and controversies in the existing literature, and we delineate research questions that must be addressed to determine whether GDF-15 can be therapeutically manipulated in other clinical settings.
| S-EPMC6543753 | biostudies-literature