Plasma Adiponectin Levels are Associated with Circulating Inflammatory Cytokines in Autoantibody Positive First-Degree Relatives of Rheumatoid Arthritis Patients
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PROVIDER: PRJNA461100 | ENA |
REPOSITORIES: ENA
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Project description:Background: Extra-articular manifestations of rheumatoid arthritis (RA), potentially due to systemic inflammation, include cardiovascular disease and sarcopenic obesity. Adiponectin, an adipose-derived cytokine, has been implicated in inflammatory processes in RA, but little is known regarding its association with inflammation in a pre-clinical period. Therefore, we investigated whether adiponectin was associated with inflammatory markers in individuals at risk for RA, and whether RA-related autoimmunity modifies these associations. Methods: We analyzed samples from 144 first-degree relatives (FDRs) of RA probands, of whom 23 were positive for anti-cyclic citrullinated peptide antibody and/or ≥ 2 rheumatoid factor isotypes (IgM, IgG or IgA). We called this phenotype the ‘high risk autoantibody profile (HRP)’ as it has been shown in prior work to be >96% specific for future RA. We measured adiponectin, cytokines/chemokines, and high-sensitivity C-reactive protein (hsCRP). Using linear mixed effects models, we evaluated interaction between HRP positivity and adiponectin on inflammatory markers, adjusting for age, sex, ethnicity, body mass index, pack-years smoking, and use of cholesterol-lowering medications. Results: In everyone, adiponectin concentration was inversely associated with hsCRP and IL-1b in adjusted models, where a 1% higher adiponectin was associated with a 26% lower hsCRP (p=0.04) and a 26% lower IL-1b (p=0.04). Significant interactions between HRP and adiponectin for associations with GM-CSF, IL-6, and IL-9 were detected in fully adjusted models (p=0.0006, p=0.006, p=0.01, respectively). In HRP positive FDRs but not HRP negative FDRs, a 1% higher adiponectin was associated with 97% higher GM-CSF, 73% higher IL-6, and 54% higher IL-9 concentrations. Conclusions: Adiponectin associates with inflammatory markers, and these associations differ in individuals with a high-risk autoantibody profile compared with those without. The interaction between adiponectin and autoimmunity may occur systemically, rather than at the joint, which may provide insight into the systemic effects of RA-related autoantibodies and inflammation in the absence of clinically apparent RA.
2018-07-01 | GSE114043 | GEO
Project description:BACKGROUND:Extra-articular manifestations of rheumatoid arthritis (RA), potentially due to systemic inflammation, include cardiovascular disease and sarcopenic obesity. Adiponectin, an adipose-derived cytokine, has been implicated in inflammatory processes in RA, but little is known regarding its association with inflammation in a pre-clinical period. Therefore, we investigated whether adiponectin was associated with inflammatory markers in individuals at risk for RA, and whether RA-related autoimmunity modifies these associations. METHODS:We analyzed samples from 144 first-degree relatives (FDRs) of RA probands, of whom 23 were positive for anti-cyclic citrullinated peptide antibody and/or ? 2 rheumatoid factor isotypes (IgM, IgG or IgA). We called this phenotype the 'high risk autoantibody profile (HRP)' as it has been shown in prior work to be >96% specific for future RA. We measured adiponectin, cytokines, and high-sensitivity C-reactive protein (hsCRP). Using linear mixed effects models, we evaluated interaction between HRP positivity and adiponectin on inflammatory markers, adjusting for age, sex, ethnicity, body mass index, pack-years smoking, and use of cholesterol-lowering medications. RESULTS:In everyone, adiponectin concentration was inversely associated with hsCRP and IL-1? in adjusted models, where a 1% higher adiponectin was associated with a 26% lower hsCRP (p = 0.04) and a 26% lower IL-1? (p = 0.04). Significant interactions between HRP and adiponectin for associations with GM-CSF, IL-6, and IL-9 were detected in fully adjusted models (p = 0.0006, p = 0.006, p = 0.01, respectively). In HRP positive FDRs but not HRP negative FDRs, a 1% higher adiponectin was associated with 97% higher GM-CSF, 73% higher IL-6, and 54% higher IL-9 concentrations. CONCLUSIONS:Adiponectin associates with inflammatory markers, and these associations differ in individuals with a high-risk autoantibody profile compared with those without. The interaction between adiponectin and autoimmunity warrants further investigation into the potential systemic effects of RA-related autoantibodies and adiponectin on inflammation in the absence of clinically apparent RA.
| S-EPMC6016921 | biostudies-literature
Project description:Patients with Celiac Disease, first degree relatives of celiac patients and control groups displayed significant differential gene expression.
2019-03-21 | GSE112102 | GEO
Project description:Type 1 Diabetes (T1D) is considered to be a Th1 autoimmune disease characterised by an absolute lack of insulin caused by an autoimmune destruction of the insulin producing pancreatic beta cells. Th1 lymphocytes are responsible for the infiltration of the islets of Langerhans and for the cytokine release that supports cytotoxic (Tc) lymphocytes to mediate destruction of the beta cells. The preclinical disease stage is characterized by the generation of the self-reactive lymphocytes that infiltrate the pancreas and selectively destroy the insulin-producing beta cells present in the islets. Other cellular immune mechanisms regarding immunoregulation and antigen presentation and processing are involved in T1D pathogenesis as well. Our aim was to identify genes involved in the corresponding signalling cascades, especially those which may serve as promising diagnostic tools for the identification of persons in the prediabetic phase of the disease. We addressed the question by analysing gene expression profiles of freshly isolated peripheral blood mononuclear cells in type 1 diabetes patients, their first degree relatives divided according to their autoantibody status, and healthy controls. 9 T1D-patients versus 10 first degree relatives versus 10 healthy controls
2011-05-09 | E-GEOD-29142 | biostudies-arrayexpress
Project description:The purpose of this study is to determine whether staining of the gastric mucosa increases the number of detected (pre)malignant foci of intestinal and diffuse type gastric cancer, in first degree relatives of individuals with familial gastric cancer.
| 2135191 | ecrin-mdr-crc
Project description:To determine the prevalence of colorectal neoplasms in first degree relatives of those affected with sporadic colorectal cancer using colonoscopy as a screening tool. The prevalence will be compared to that of a defined matched cohort.
| 2016878 | ecrin-mdr-crc
Project description:BACKGROUND: First-degree relatives of patients with colorectal cancer are at increased risk for colorectal cancer as well. Nevertheless, participation in the German national screening program stagnates at 2-3 percent per year even in this high-risk population.
AIM: The study is aimed to increase the portion of the first-degree relatives on 50% which take up a preventive colonoscopy.
METHODS: Cluster-randomized controlled multi-center trial. Study sites (clusters) are mainly certified cancer centers and office-based gastroenterologists from all over Germany. Index-patients with colorectal cancer of different stages are asked to hand over the study material to their relatives, consisting of an invitation to a nurse-led counseling on preventive colonoscopy and an one-to-one appointment with a clinical expert of one of the study sites next.
| 2148616 | ecrin-mdr-crc
Project description:BackgroundDespite immune cell dysregulation being an important event preceding the onset of rheumatoid arthritis (RA), the phenotype of T and B cells in preclinical RA is less understood. The aim of this study was to characterize T and B cell populations in RA patients and their autoantibody (aAb) negative and positive first-degree relatives (FDR).MethodsCryopreserved peripheral blood mononuclear cells (PBMCs) collected at scheduled visits from aAb-(n=25), and aAb+ FDR (n=10) and RA patients (n=13) were thawed and stained using optimized antibody cocktails as per a specific 13-color T or B cell panel. Immunophenotyping was performed using a Cytoflex LX (Beckman-Coulter) flow cytometer and FlowJo software was used for analyzing the frequency of immune cell populations.ResultsMulticolor flow cytometry experiments identified an increased TIGIT expression in circulating lymphocytes of aAb+ FDR and RA patients, relative to aAb- FDR (P<0.01). These TIGIT+ T cells exhibited a memory phenotype and expressed high levels of PD-1, ICOS, HLA-DR, CXCR3 and CXCR5. Moreover, increased TIGIT+ CD4 T cell frequency correlated with the frequency of PD-1+ CD4 T cells (r = 0.4705: P = 0.0043) and circulating levels of ACPA and RF. We also identified a decreased frequency of CD27+IgD- switched memory B cells in RA patients (P < 0.01), while increased frequency of TIGIT+ CD4 T cells in FDR correlated with the frequency of PD1+PTEN+ B cells (r = 0.6838, P = 0.0004) and autoantibody positivity (P = 0.01).ConclusionWe demonstrate TIGIT as a distinct CD4 T cell marker for differentiating aAb- FDR from aAb+FDR and might play a critical role in regulating T and B cell crosstalk in preclinical RA.
| S-EPMC9366176 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE32016: Autoantibody Epitope Spreading in the Pre-Clinical Phase Predicts Progression to Rheumatoid Arthritis [ANALYTE: ANTIGEN] GSE32019: Autoantibody Epitope Spreading in the Pre-Clinical Phase Predicts Progression to Rheumatoid Arthritis [ANALYTE: Cytokine or chemokine] Refer to individual Series
2011-09-09 | E-GEOD-32021 | biostudies-arrayexpress
Project description:The risk of CRC in families of patients with CRC is well established, but it is less well-defined for families of patients with adenomas. Screening recommendations to families when an index subject has an adenoma on colonoscopy are not clear. Previous studies demonstrating an increased CRC risk in close relatives of subjects with adenomas were mostly limited by the lack of a suitable comparison group, did not offer colonoscopy to all relatives or did not have verification on true status of adenoma history in the relatives. A systematic review has reported that most studies cited for risk of CRC in relatives with adenomas have not addressed the intended question. Currently International guidelines recommended screening colonoscopy in close relatives and at a younger age when there is a proband with an adenoma, however this recommendation has not been fully supported by all societies due to the lack of robust evidence. This gap in knowledge highlights the need of well-designed and adequately powered studies to estimate the risk of colorectal neoplasms in subjects who have first-degree relatives with adenomas.
Up to 30% of average risk asymptomatic individuals 50 years or older will have at least one adenoma. Based on current guidelines, nearly half the population will be counseled to undergo a colonoscopy from 40 years old based on a positive family history of adenoma. This will have enormous burden on the healthcare system if screening is implicated in all these individuals. Secondly, not all adenomas carry the same risk. Large or villous adenomas are associated with a nearly 70% increased risk of CRC in first degree relatives (FDR) whereas small adenomas may be associated with a modest increased risk 19. It is therefore important to determine the risk of colorectal neoplasms in families of subjects with non-advanced adenomas to justify more intensive screening in these individuals. Investigators hypothesize that first-degree relatives of patients with non-advanced adenoma have an increased risk of both CRC and adenomas. Investigators aim to quantify this risk, and to identify other individual patient or neoplasm characteristics that may contribute to this increased risk. In addition, Investigators aim to determine molecular alteration profiles of colonic adenoma in siblings of patients with advanced neoplasm.
| 2195959 | ecrin-mdr-crc