Nejvíce citovaný článek - PubMed ID 10521989
Inflammatory bowel diseases (IBD) are systemic immune-mediated conditions with predilection for the gastrointestinal tract and include Crohn's disease and ulcerative colitis. Despite the advances in the fields of basic and applied research, the etiopathogenesis remains largely unknown. As a result, only one third of the patients achieve endoscopic remission. A substantial portion of the patients also develop severe clinical complications or neoplasia. The need for novel biomarkers that can enhance diagnostic accuracy, more precisely reflect disease activity, and predict a complicated disease course, thus, remains high. Genomic and transcriptomic studies contributed substantially to our understanding of the immunopathological pathways involved in disease initiation and progression. However, eventual genomic alterations do not necessarily translate into the final clinical picture. Proteomics may represent a missing link between the genome, transcriptome, and phenotypical presentation of the disease. Based on the analysis of a large spectrum of proteins in tissues, it seems to be a promising method for the identification of new biomarkers. This systematic search and review summarize the current state of proteomics in human IBD. It comments on the utility of proteomics in research, describes the basic proteomic techniques, and provides an up-to-date overview of available studies in both adult and pediatric IBD.
- Klíčová slova
- Crohn’s disease, inflammatory bowel disease, pediatric, proteome, proteomics, ulcerative colitis,
- MeSH
- biologické markery metabolismus MeSH
- Crohnova nemoc * metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- idiopatické střevní záněty * metabolismus MeSH
- lidé MeSH
- proteomika metody MeSH
- ulcerózní kolitida * metabolismus MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
Neutrophils impact on processes preceding the formation of bradykinin, a major swelling mediator in hereditary angioedema (HAE), yet their potential role in HAE pathogenesis has not been sufficiently studied. We assessed the relative mRNA expression of 10 genes related to neutrophil activation using RNA extracted from the peripheral blood neutrophils of 23 HAE patients in a symptom-free period and 39 healthy donors. Increased relative mRNA expression levels of CD274, IL1B, IL1RN, IL8, MMP9, and TLR4, together with a lack in their mutual correlations detected in HAE patients compared to healthy controls, suggested a preactivated state and dysregulation of patients' neutrophils. Patients' neutrophil-alerted state was further supported by increased CD11b, decreased CD16 plasma membrane deposition, and increased relative CD274+ and CD87+ neutrophil counts, but not by increased neutrophil elastase or myeloperoxidase plasma levels. As CD274 mediates inhibitory signals to different immune cells, neutrophils were cocultured with T-cells/PBMC. The decrease in CD25+ and IFN-γ + T-cell/PBMC ratio in patients indicated the patients' neutrophil suppressive functions. In summary, the results showed neutrophils' alerted state and dysregulation at the transcript level in patients with HAE types I and II even in a symptom-free period, which might make them more susceptible to edema formation. Neutrophils' T-cell suppressive capacity in HAE patients needs to be further investigated.
- MeSH
- antagonista receptoru pro interleukin 1 metabolismus MeSH
- antigeny CD11b metabolismus MeSH
- antigeny CD274 metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- ELISA MeSH
- hereditární angioedém, typy I a II metabolismus MeSH
- interleukin-1beta metabolismus MeSH
- interleukin-8 metabolismus MeSH
- kultivované buňky MeSH
- leukocyty mononukleární metabolismus MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 metabolismus MeSH
- messenger RNA MeSH
- mladiství MeSH
- mladý dospělý MeSH
- neutrofily metabolismus MeSH
- pankreatická elastasa krev MeSH
- peroxidasa krev MeSH
- průtoková cytometrie MeSH
- receptory IgG metabolismus MeSH
- receptory urokinázového aktivátoru plazminogenu metabolismus MeSH
- toll-like receptor 4 metabolismus MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antagonista receptoru pro interleukin 1 MeSH
- antigeny CD11b MeSH
- antigeny CD274 MeSH
- IL1B protein, human MeSH Prohlížeč
- IL1RN protein, human MeSH Prohlížeč
- interleukin-1beta MeSH
- interleukin-8 MeSH
- matrixová metaloproteinasa 9 MeSH
- messenger RNA MeSH
- pankreatická elastasa MeSH
- peroxidasa MeSH
- receptory IgG MeSH
- receptory urokinázového aktivátoru plazminogenu MeSH
- toll-like receptor 4 MeSH
Common variable immunodeficiency disorders (CVIDs) represent a group of primary immunodeficiency diseases characterized by hypogammaglobulinemia and dysfunctional immune response to invading pathogens. Previous studies have indicated that CVID is associated with microbial translocation and systemic myeloid cell activation. The goal of this study was to determine whether patients with CVID display elevated systemic levels of markers of granulocyte activation and whether the levels are further influenced by intravenous immunoglobulin (IVIg) infusions. The plasma levels of granulocyte activation markers elastase and myeloperoxidase were determined using enzyme-linked immunosorbent assay (ELISA) in 46 CVID patients and 44 healthy controls. All CVID patients were in a stable state with no apparent acute infection. In addition, granulocyte activation markers' plasma levels in 24 CVID patients were determined prior to and 1 h following IVIg administration. Neutrophil elastase and myeloperoxidase plasma levels were significantly higher in CVID patients than in healthy controls. Systemic elastase levels were further increased following IVIg administration. In vitro stimulation of 13 CVID patients' whole blood using IVIg in a therapeutically relevant dose for 2 h resulted in a significant increase in plasma elastase levels compared to unstimulated blood. The data presented here indicate that CVID is associated with chronic granulocytic activation which is further exacerbated by administering IVIg. Increased myeloperoxidase and elastase levels may contribute to associated comorbidities in CVID patients.
- Klíčová slova
- CVID, elastase, immunoglobulin treatment, myeloperoxidase, neutrophil activation,
- MeSH
- běžná variabilní imunodeficience krev diagnóza farmakoterapie MeSH
- biologické markery krev MeSH
- dospělí MeSH
- intravenózní imunoglobuliny aplikace a dávkování MeSH
- leukocytární elastasa krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- peroxidasa krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- intravenózní imunoglobuliny MeSH
- leukocytární elastasa MeSH
- peroxidasa MeSH