Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA107855 | ENA |
REPOSITORIES: ENA
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Project description:The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D and HC cohorts. In addition, we examined T1D progression by looking at longitudinal, pre-onset and longstanding T1D samples. UPN727 cells were stimulated with autologous plasma (n=7), unrelated healthy control plasma (n=44), recent onset T1D plasma (n=46), longstanding T1D plasma (n=11), or longitudinal series plasma (n=6 time points) from pre/post onset. Gene expression analysis was performed in order to evaluate the transcriptional signature associated with T1D.
2012-09-01 | E-GEOD-35725 | biostudies-arrayexpress
Project description:Dysbiosis of the gut microbiota has been linked to disease pathogenesis in type 1 diabetes (T1D), yet the functional consequences to the host of this dysbiosis is unknown. Here, we have performed a metaproteomic analysis of 103 stool samples from subjects that either had recent-onset T1D, were high-risk autoantibody positive or low-risk autoantibody negative relatives of individuals with beta cell autoimmunity or healthy individuals to identify signatures in host and microbial proteins associated with disease risk. Multivariate modelling analysis demonstrated that both human host proteins and microbial derived proteins could be used to differentiate new-onset and seropositive individuals from low-risk and healthy controls. Significant alterations were identified between subjects with T1D or islet autoimmunity versus autoantibody negative and control subjects in the prevalence of individual host proteins associated with exocrine pancreas function, inflammation and mucosal function. Data integrationIntegrative analysis combining the metaproteomic data with bacterial abundance showed that taxa that were depleted in new-onset T1D patients were positively associated with host proteins involved in maintaining function of the mucous barrier, microvilli adhesion and exocrine pancreas. These data support the notion that T1D patients have increased intestinal inflammation and decreased barrier function. They also confirmed that pancreatic exocrine dysfunction occurs in new-onset T1D patients and show for the first time that this dysfunction is present in high-risk individuals prior to disease onset. Our data has identified a unique T1D-associated signature in stool that may be useful as a means to monitor disease progression or response to therapies aimed at restoring a healthy microbiota.
2018-11-07 | PXD008870 | Pride
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
2014-12-02 | GSE63741 | GEO
Project description:The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D and HC cohorts. In addition, we examined T1D progression by looking at longitudinal, pre-onset and longstanding T1D samples.
2012-09-01 | GSE35725 | GEO
Project description:The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D, HC, and healthy T1D sibling cohorts. In addition, we examined T1D progression by looking at longitudinal samples. UPN727 cells were stimulated with Auto-antibody-negative (AA-) High HLA Risk Siblings plasma (n=30), Auto-antibody-negative (AA-) Low HLA Risk Siblings plasma (n=42), Recent onset T1DM plasma cultured with IL1RA (n=42), or longitudinal series plasma on T1DM progressor (n=27 chips, 5 series), on auto-antibody-positive (AA+) High HLA Risk Siblings (n=54 chips, 9 series), on auto-antibody-negative (AA-) High HLA Risk Siblings (n=60 chips, 12 series), on auto-antibody-negative (AA-) Low HLA Risk Siblings (n=31 chips, 6 series). Gene expression analysis was perfromed in order to evaluate the transcriptional signature associated with T1D.
2014-05-13 | E-GEOD-52724 | biostudies-arrayexpress
Project description:Changes in innate and adaptive immunity occurring in and around pancreatic islets can also be observed in peripheral blood mononuclear cells (PBMC) of T1D patients in Caucasians. The aim of our study was to investigate whether gene expression patterns of PBMC could complement islet autoantibodies for T1D pathogenic mechanisms in the higlty admixed Brazilian population. Methods: We assessed global gene expression in PBMC from two groups mached for age, sex and BMI: The T1D group with 20 patients with recent-onset T1D (≤ 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls (Control group). Results: we identified 474 differentially expressed genes between groups. The most expressed genes in T1D group were mainly related to host defense, with inflammatory and anti-bacterial/antiviral effects ( LFT, DEFA4, DEFA1, CTSG, KCNMA1) as well as to cell cycle progression. Several of the downregulated genes in T1D influenced cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression (AREG) and immune tolerance (SMAD6). Conclusion: Our analysis suggested the activation of cell cycle/proliferation, anti-infectious and inflammatory pathways, indicating immune activation, whereas immunoregulatory pathways were downregulated in PBMC from recent-onset T1D patients. These alterations were elicited by a new genetic profile
2022-01-01 | GSE156035 | GEO
Project description:Proteomic data from recent onset T1D patients treated with verapamil where significant extension of the honeymoon phase was observed. Samples were depleted with MARS Hu-14 column, digested with trypsin, labeled with 11-plex TMT, then analyzed by LC-MS/MS. Data was searched with MS-GF+ using PNNL's DMS Processing pipeline. TMT data was extracted using PlexedPiper.
2021-06-09 | MSV000087598 | MassIVE
Project description:The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D, HC, and healthy T1D sibling cohorts. In addition, we examined T1D progression by looking at longitudinal samples.
2014-05-13 | GSE52724 | GEO
Project description:A need exists for biomarkers in T1D that can 1) sensitively and specifically detect disease-related immune activity prior to, and independent of, measurement of auto-antibodies towards islet cell antigens; 2) define immunopathological mechanisms; and 3) monitor changes in the inflammatory state associated with disease progression or response to therapeutic intervention. In an effort to fill this gap, we have applied a novel bioassay to both human and BB rat T1D whereby the complex milieu of inflammatory mediators present in plasma can be indirectly detected through their ability to drive transcription in peripheral blood mononuclear cells drawn from healthy, unrelated donors. The resultant gene expressions are comprehensively measured with a microarray. In our human studies, we find that plasma of recent-onset T1D patients induces expression of a pro-inflammatory signature consisting in part of many interleukin-1 (IL-1) regulated genes related to immunological activation and immunocyte chemotaxis compared to unrelated healthy controls. This signature has been found to resolve in long-standing T1D subjects (>10 years post-onset), thus associating it with active autoimmunity. Importantly, this signature has been detected in pre-onset samples of progressors to T1D years prior to onset and prior to development of auto-antibodies directed towards islet antigens. Fresh PBMCs of a healthy control donor were isolated by density gradient centrifugation. These cells were then stimulated with 20% plasma from a longitudinally monitored sibling of a T1D patient that progressed to T1D (n= 6 timepoints) at 37C in 5% CO2. Gene expression analysis was perfromed in order to evaluate the transcriptional signature associated with T1D pathogenesis.
2013-06-01 | E-GEOD-40496 | biostudies-arrayexpress
Project description:Background Changes in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms. METHODS: We assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (≤ 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls. RESULTS: We identified 474 differentially expressed genes between groups. The most expressed genes in T1D group favored host defense, inflammatory and anti-bacterial/antiviral effects (LFT, DEFA4, DEFA1, CTSG, KCNMA1) and cell cycle progression. Several of the downregulated genes in T1D target cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression (AREG) and immune tolerance (SMAD6). SMAD6 expression correlated negatively with islet ZnT8 antibody. The expression of PDE12, that offers resistance to viral pathogens was decreased and negatively related to ZnT8A and GADA levels. The increased expression of long non coding RNAs MALAT1 and NEAT1, related to inflammatory mediators, autoimmune diseases and innate immune response against viral infections reinforced these data CONCLUSIONS: Our analysis suggested the activation of cell development, anti-infectious and inflammatory pathways, indicating immune activation, whereas immune-regulatory pathways were downregulated in PBMC from recent-onset non-Caucasian T1D patients with a different genetic profile.
2022-01-08 | GSE193273 | GEO