185: Immune cell bound MUC16: evidence supporting the use of immune transcriptomes and proteomes as reservoirs for disease specific biomarkers

Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso.

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Defining the Microglia Response during the Time Course of Chronic Neurodegeneration

Journal of Virology ◽

10.1128/jvi.02613-15 ◽

2015 ◽

Vol 90 (6) ◽

pp. 3003-3017 ◽

Cited By ~ 41

Author(s):

James E. Vincenti ◽

Lita Murphy ◽

Kathleen Grabert ◽

Barry W. McColl ◽

Enrico Cancellotti ◽

...

Keyword(s):

Prion Disease ◽

Time Course ◽

Inflammatory Process ◽

Immune Cell ◽

Disease Model ◽

Disease Process ◽

Immune Cell Population ◽

The Brain ◽

Disease Specific

ABSTRACTInflammation has been proposed as a major component of neurodegenerative diseases, although the precise role it plays has yet to be defined. We examined the role of key contributors to this inflammatory process, microglia, the major resident immune cell population of the brain, in a prion disease model of chronic neurodegeneration. Initially, we performed an extensive reanalysis of a large study of prion disease, where the transcriptome of mouse brains had been monitored throughout the time course of disease. Our analysis has provided a detailed classification of the disease-associated genes based on cell type of origin and gene function. This revealed that the genes upregulated during disease, regardless of the strain of mouse or prion protein, are expressed predominantly by activated microglia. In order to study the microglia contribution more specifically, we established a mouse model of prion disease in which the 79A murine prion strain was introduced by an intraperitoneal route into BALB/cJFms-EGFP/−mice, which express enhanced green fluorescent protein under the control of thec-fmsoperon. Samples were taken at time points during disease progression, and histological analysis of the brain and transcriptional analysis of isolated microglia was carried out. The analysis of isolated microglia revealed a disease-specific, highly proinflammatory signature in addition to an upregulation of genes associated with metabolism and respiratory stress. This study strongly supports the growing recognition of the importance of microglia within the prion disease process and identifies the nature of the response through gene expression analysis of isolated microglia.IMPORTANCEInflammation has been proposed as a major component of neurodegenerative diseases. We have examined the role of key contributors to this inflammatory process, microglia, the major resident immune cell population of the brain, in a murine prion disease model of chronic neurodegeneration. Our study demonstrates that genes upregulated throughout the disease process are expressed predominantly by microglia. A disease-specific, highly proinflammatory signature was observed in addition to an upregulation of genes associated with metabolism and respiratory stress. This study strongly supports the growing recognition of the important contribution of microglia to a chronic neurodegenerative disease process.

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Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

Frontiers in Immunology ◽

10.3389/fimmu.2020.00288 ◽

2020 ◽

Vol 11 ◽

Cited By ~ 3

Author(s):

Louise Magnusson ◽

Hugo Barcenilla ◽

Mikael Pihl ◽

Sophie Bensing ◽

Daniel Espes ◽

...

Keyword(s):

Immune Cell ◽

Mass Cytometry ◽

Endocrine Diseases ◽

Immune Cell Subsets ◽

Distinct Disease ◽

Disease Specific

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Identification of Disease-Specific Hub Biomarkers and Immune Infiltration in Osteoarthritis and Rheumatoid Arthritis Synovial Tissues by Bioinformatics Analysis

Disease Markers ◽

10.1155/2021/9911184 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Fei Sun ◽

Jian lin Zhou ◽

Pu ji Peng ◽

Chen Qiu ◽

Jia rui Cao ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Immune Cells ◽

Bioinformatics Analysis ◽

Immune Cell ◽

Relative Proportion ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Hub Genes ◽

Synovial Tissues ◽

Disease Specific

Background. Osteoarthritis (OA) and rheumatoid arthritis (RA) are well-known cause of joint disability. Although they have shown the analogous clinical features involving chronic synovitis that progresses to cartilage and bone destruction, the pathogenesis that initiates and perpetuates synovial lesions between RA and OA remains elusive. Objective. This study is aimed at identifying disease-specific hub genes, exploring immune cell infiltration, and elucidating the underlying mechanisms associated with RA and OA synovial lesion. Methods. Gene expression profiles (GSE55235, GSE55457, GSE55584, and GSE12021) were selected from Gene Expression Omnibus for analysis. Differentially expressed genes (DEGs) were identified by the “LIMMA” package in Bioconductor. The DEGs were identified by Gene Ontology (GO) and KEGG pathway analysis. A protein-protein interaction network was constructed to identify candidate hub genes by using STRING and Cytoscape. Hub genes were identified by validating from GSE12021. Furthermore, we employed the CIBERSORT website to assess immune cell infiltration between OA and RA. Finally, we explored the correlation between the levels of hub genes and relative proportion of immune cells in OA and RA. Results. We identified 68 DEGs which were mainly enriched in immune response and chemokine signaling pathway. Six hub genes with a cutoff of AUC > 0.80 by ROC analysis and relative expression of P < 0.05 were identified successfully. Compared with OA, the RA synovial tissues consisted of a higher proportion of 7 immune cells, whereas 4 immune cells were found in relatively lower proportion ( P < 0.05 ). In addition, the levels of 6 hub genes were closely associated with relative proportion of 11 immune cells in OA and RA. Conclusions. We used bioinformatics analysis to identify hub genes and explored immune cell infiltration of immune microenvironment in synovial tissues. Our results should offer insights into the underlying molecular mechanisms of synovial lesion and provide potential target for immune-based therapies of OA and RA.

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Plasma cell marker, immunoglobulin J polypeptide, predicts early disease-specific mortality in HPV+ HNSCC

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001259 ◽

2021 ◽

Vol 9 (3) ◽

pp. e001259

Author(s):

Shanying Gui ◽

W Quinn O'Neill ◽

Theodoros N Teknos ◽

Quintin Pan

Keyword(s):

Plasma Cells ◽

Immune Cell ◽

Cox Regression ◽

Prognostic Biomarker ◽

The Cancer Genome Atlas ◽

Definitive Treatment ◽

Early Disease ◽

Specific Mortality ◽

Disease Specific Mortality ◽

Disease Specific

BackgroundPatients with human papillomavirus (HPV+) head and neck squamous cell carcinoma (HNSCC) have superior prognoses compared with patients with HPV− HNSCC and strategies for treatment de-escalation are under investigation for the HPV+ setting. However, the survival advantage associated with HPV is not universal, and a subset of patients with HPV+ HNSCC fail definitive treatment and progress with metastatic/recurrent disease. Currently, no biomarker is available to distinguish aggressive from indolent HPV+ HNSCC. Immune dysfunction facilitates tumorigenesis and is associated with poor treatment response; therefore, we hypothesized that diminished intratumoral immune cell functionality may be attractive biomarkers to identify patients with HPV+ HNSCC at risk for early disease-specific mortality.MethodsThis is a retrospective analysis of The Cancer Genome Atlas (TCGA) HPV+ HNSCC cohort.ResultsImmunoglobulin J polypeptide (IGJ), uniquely expressed in plasma cells, showed a broad expression range in HPV+ HNSCC. Cox regression model, adjusting for clinical covariates, indicated that IGJ is an independent prognostic biomarker for disease-specific survival (DSS) and overall survival (OS). Patients with low IGJ had a 7.2-fold (p<0.001) increase in risk of disease-specific death with a median DSS of 13 months. Low IGJ showed an area under curve (AUC) of 0.89 with 91.0% sensitivity and 87.6% specificity to identify early disease-specific mortality (defined as DSS ≤12 months). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed a global dampening of immune pathways in low IGJ tumors.ConclusionsOur work showed that IGJ is a robust and independent prognostic biomarker for disease-specific mortality in HPV+ HNSCC. Patient with HPV+ HNSCC with limited adaptive immune functionality should not be candidates for treatment de-escalation modalities.

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Untargeted Metabolomic Profiling Identifies Disease-specific Profiles in Food Allergy

10.1101/657866 ◽

2019 ◽

Author(s):

E Crestani ◽

Hani Harb ◽

Louis Marie Charbonnier ◽

J Leirer ◽

A Motsinger-Reif ◽

...

Keyword(s):

Food Allergy ◽

Immune Cell ◽

Treatment Options ◽

Bile Acid Metabolism ◽

Metabolomic Profile ◽

Serum Samples ◽

Secondary Bile Acid ◽

Metabolomic Profiling ◽

The Face ◽

Disease Specific

AbstractBackgroundFood allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Identification of pathogenic mechanisms involved in FA using untargeted metabolomic approaches may provide much needed diagnostic and prognostic disease biomarkers and improved treatment options.MethodsMass spectrometry-based untargeted metabolomic profiling was performed on serum samples of children with either FA alone, asthma alone or both FA and asthma as well as healthy pediatric controls.ResultsFA subjects exhibited a disease-specific metabolomic signature as compared to both control subjects and asthmatics. In particular, FA was uniquely associated with a marked decrease in sphingolipids, as well as a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T (NKT) cells. Specific comparison of FA and asthmatic subjects revealed differences in the microbiota-sensitive aromatic amino acid and secondary bile acid metabolism. Children with both FA and asthma exhibited a metabolomic profile that aligned with that of FA alone but not asthma. Among children with FA, distinct profiles were associated with history of severe reactions and presence of multiple FA.ConclusionsChildren with FA display a disease-specific metabolomic profile that is informative of disease mechanisms and severity, and which dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in FA children may reflect the interplay between an altered microbiota and immune cell subsets in the gut.

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