scholarly journals Effects of In Vivo Gluten Challenge on PBMC Gene Expression Profiles in Diet Treated Celiac Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Dawit A. Yohannes ◽  
Andrea de Kauwe ◽  
Katri Kaukinen ◽  
Kalle Kurppa ◽  
Markku Mäki ◽  
...  
Keyword(s):  
Immune Response ◽  
Celiac Disease ◽  
Unsaturated Fatty Acids ◽  
Clinical Symptoms ◽  
Expression Profiles ◽  
Biological Pathways ◽  
Clear Understanding ◽  
Intestinal Damage ◽  
Healthy Controls ◽  
Wide Range

The pathological mechanisms that lead to the onset and reactivation of celiac disease (CD) remain largely unknown. While gluten free diet (GFD) improves the intestinal damage and associated clinical symptoms in majority of cases, it falls short of providing full recovery. Additionally, late or misdiagnosis is also common as CD presents with a wide range of symptoms. Clear understanding of CD pathogenesis is thus critical to address both diagnostic and treatment concerns. We aimed to study the molecular impact of short gluten exposure in GFD treated CD patients, as well as identify biological pathways that remain altered constitutively in CD regardless of treatment. Using RNAseq profiling of PBMC samples collected from treated CD patients and gluten challenged patient and healthy controls, we explored the peripheral transcriptome in CD patients following a short gluten exposure. Short gluten exposure of just three days was enough to alter the genome-wide PBMC transcriptome of patients. Pathway analysis revealed gluten-induced upregulation of mainly immune response related pathways, both innate and adaptive, in CD patients. We evaluated the perturbation of biological pathways in sample-specific manner. Compared to gluten exposed healthy controls, pathways related to tight junction, olfactory transduction, metabolism of unsaturated fatty acids (such as arachidonic acid), metabolism of amino acids (such as cysteine and glutamate), and microbial infection were constitutively altered in CD patients regardless of treatment, while GFD treatment appears to mostly normalize immune response pathways to “healthy” state. Upstream regulator prediction analysis using differentially expressed genes identified constitutively activated regulators relatively proximal to previously reported CD associated loci, particularly SMARCA4 on 19p13.2 and CSF2 on 5q31. We also found constitutively upregulated genes in CD that are in CD associated genetic loci such as MEF2BNB-MEF2B (BORCS8-MEF2B) on 19p13.11 and CSTB on 21q22.3. RNAseq revealed strong effects of short oral gluten challenge on whole PBMC fraction and constitutively altered pathways in CD PBMC suggesting important factors other than gluten in CD pathogenesis.

scholarly journals Early Response of CD8+ T Cells in COVID-19 Patients

2021 ◽  
Vol 11 (12) ◽  
pp. 1291
Author(s):  
Deni Ramljak ◽  
Martina Vukoja ◽  
Marina Curlin ◽  
Katarina Vukojevic ◽  
Maja Barbaric ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Mrna Expression ◽  
Cd8 T Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Effector Memory ◽  
Healthy Controls ◽  
Ifn Γ

Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes (p = 0.007), CD3+ (p = 0.05), and CD8+ T cells (p = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) (p = 0.06) and effector memory 4 (EM4) (p < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 (p = 0.05) and lower mRNA expression of FASL (p = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 (p < 0.001) and IFN-γ (p < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK (p < 0.01) and FASL (p < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease.

scholarly journals Immunization with SARS-CoV-2 nucleocapsid protein triggers a pulmonary immune response in rats

2021 ◽  
Author(s):  
Everidiene K. V. B. Silva ◽  
Camila G. Bomfim ◽  
Ana P. Barbosa ◽  
Paloma Noda ◽  
Irene L. Noronha ◽  
...  
Keyword(s):  
Immune Response ◽  
Recombinant Proteins ◽  
Research Group ◽  
Nucleocapsid Protein ◽  
Clinical Symptoms ◽  
Multiple Organ ◽  
World Population ◽  
Emerging Viruses ◽  
Wide Range ◽  
Different Strains

ABSTRACTThe SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce specific pulmonary protection.

scholarly journals Antigen distribution of TMUV and GPV are coincident with the expression profiles of CD8α-positive cells and goose IFNγ

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hao Zhou ◽  
Shun Chen ◽  
Mingshu Wang ◽  
Renyong Jia ◽  
Dekang Zhu ◽  
...  
Keyword(s):  
Immune Response ◽  
Small Intestine ◽  
Proinflammatory Cytokines ◽  
Clinical Symptoms ◽  
Expression Profiles ◽  
Immune Genes ◽  
Fundamental Information ◽  
Causative Agents ◽  
Goose Parvovirus ◽  
Immune Related Genes

Abstract Both Tembusu virus (TMUV) and goose parvovirus (GPV) are causative agents of goose disease. However, the host immune response of the goose against these two different categories of virus has not been well documented. Here, we compared the clinical symptoms and pathological characteristics, antigen distribution and intensity, and expression of immune-related genes in TMUV- and GPV- infected goose. The immunohistochemistry analysis demonstrated that GPV was primarily located in the liver, lung, small intestine, and rectum, while TMUV was situated in the liver, brain, spleen, and small intestine. The induction of IFNγ and proinflammatory cytokines is highly associated with the distribution profiles of antigen and CD8α+ molecules. The effector function of CD8 T cells may be accomplished by the secretion of IFNγ together with high expression of proinflammatory cytokines such as IL1 and IL6. Remarkably, significant increases in the transcription of immune genes were observed after infection, which suggested that both GPV and TMUV can effectively induce immune response in goose PMBCs. This study will provide fundamental information for goose molecular immunology in defending against pandemic viruses.

scholarly journals Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat

2021 ◽  
Vol 22 (8) ◽  
pp. 4292
Author(s):  
Ana Madeira ◽  
Carolina Serena ◽  
Miriam Ejarque ◽  
Elsa Maymó-Masip ◽  
Monica Millan ◽  
...  
Keyword(s):  
Immune Response ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wilms Tumor ◽  
Expression Profiles ◽  
Subcutaneous Fat ◽  
Hla Dr ◽  
Wide Range ◽  
Antigen Presenting

Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn’s disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn’s disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms’ tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn’s disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen—DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR dim, whereas in Crohn’s disease, the HLA-DR bright subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn’s disease precursors activated CD4+ T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn’s disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response.

scholarly journals Celiac Disease or Gluten Sensitivity? A Mini Update Review

2017 ◽  
Vol 2 (2) ◽  
pp. 58
Author(s):  
Dimitrios Papandreou
Keyword(s):  
Immune Response ◽  
Celiac Disease ◽  
Similar Condition ◽  
Clinical Symptoms ◽  
Correct Diagnosis ◽  
The Other ◽  
Diagnosis And Treatment ◽  
Gluten Sensitivity ◽  
Food Items ◽  
Antigenic Properties

Celiac disease is described when some people have with foods that contain gluten. Gluten is a type of protein. It's found in the grains wheat, barley and rye. It has antigenic properties and usually triggers an immune response. On the other hand, gluten sensitivity or intolerance is a similar condition that causes a person to react to gluten found in the above food items described.Even though the clinical symptoms are similar to both conditions, the pathology, diagnosis and treatment is different, thus it is very important to get the correct diagnosis. The purpose of this mini review is to compare the main aspects of these two conditions. 

Gluten-Free Dry Mixtures with Rice and Amaranth for Children over Three Years Old with Gluten Intolerance

Food Industry ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 23-31
Author(s):  
Sergey Urubkov ◽  
Svetlana Khovanskaya ◽  
Ekaterina Pyrieva ◽  
Olga Georgieva ◽  
Stanislav Smirnov
Keyword(s):  
Celiac Disease ◽  
Treatment Effectiveness ◽  
Raw Materials ◽  
Calculated Data ◽  
Limited Range ◽  
Gluten Free ◽  
Fruit And Vegetable ◽  
Organoleptic Evaluation ◽  
Free Products ◽  
Wide Range

Diet therapy is one of the main approaches to the treatment of a wide range of diseases of the digestive system. The treatment effectiveness of celiac disease depends on how strictly the patient adheres to a gluten-free diet. It is often disrupted due to the limited range of recommended foods and dishes, especially for children who are particularly sensitive to dietary restrictions. In this case, the development of new types of specialized gluten-free products is relevant, allowing to expand the diet both in terms of nutritional value and taste diversity. This study concerns the recipe developments of dry gluten-free mixtures using rice and amaranth with the inclusion of fruit and vegetable and berry raw materials intended for the nutrition of children over three years old suffering from celiac disease. When developing the recipes, researchers used various combinations of rice and amaranth flour, as well as fruit and vegetable powders. The rice flour composition varied in the range from 15 to 75%; amaranth – from 15 to 45%; fruit and vegetable and berry powders – up to 10%. The finished product was gluten-free cookies, muffins, pancakes made of rice and amaranth. Organoleptic evaluation showed that the studied samples of gluten-free cookies have high quality characteristics, have a pleasant taste and aroma. According to the calculated data, specialized gluten-free dry mixtures intended for children over three years with celiac disease can serve as an important source of: vegetable carbohydrates – from 26.81 to 55.19 g / 100g of finished products; protein – from 4.06 to 11.82 g/100g of finished products; dietary fiber – from 3.82 to 6.36 g/100g of finished products; and energy – from 158.12 to 333.96 kcal/100g of finished products) The developed recipess of gluten-free products can help to provide children with an adequate amount of nutrients and energy.

Celiac Disease in Kosovar Albanian Children: Evaluation of Clinical Features and Diagnosis

2020 ◽  
Vol 16 (3) ◽  
pp. 241-247
Author(s):  
Atifete Ramosaj-Morina ◽  
Alije Keka-Sylaj ◽  
Arbana Baloku Zejnullahu ◽  
Lidvana Spahiu ◽  
Virgjina Hasbahta ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Dominant Mode ◽  
Primary School Children ◽  
Cross Sectional ◽  
Classical Form ◽  
Wide Range ◽  
The Mean

Background: Celiac disease is an immune-mediated disorder characterized by variable clinical manifestations, specific antibodies, HLA-DQ2/DQ8 haplotypes, and enteropathy. Objectives: The aim of this study was to present the clinical spectrum and patterns of celiac disease in Kosovar Albanian children. Methods: A cross-sectional retrospective study was performed with Albanian children aged 0-18 years, treated for celiac disease in the Pediatric Clinic, University Clinical Center of Kosovo from 2005 to 2016. Results: During the study period, 63 children were treated for celiac disease. The mean age at diagnosis was 5.5 years (SD ± 3.31). The mean age at celiac disease onset was 3.3 years (SD ± 2.02), while the mean delay from the first symptoms indicative of celiac disease to diagnosis was 2.2 years (SD ± 2.09). More than 70% of the patients were diagnosed in the first 7 years of life, mainly presented with gastrointestinal symptoms, while primary school children and adolescents mostly showed atypical symptoms (p<0.001). The classical form of celiac disease occurred in 78% of the cases. Sixty (95%) patients carried HLA-DQ2.5, DQ2.2 and/or HLA-DQ8 heterodimers, and only three of them tested negative. Conclusions: Kosovo, as the majority of developing countries, is still facing the classical form of celiac disease as the dominant mode of presentation; as a result, most children with other forms of the celiac disease remain undiagnosed. : Physicians should be aware of the wide range of clinical presentations and utilize low testing thresholds in order to prevent potential long-term problems associated with untreated celiac disease.

Occupational and Environmental Health

2017 ◽  
Keyword(s):  
Public Health ◽  
Occupational Health ◽  
Environmental Health ◽  
Health And Safety ◽  
Practical Experience ◽  
Global Perspective ◽  
Clear Understanding ◽  
Practical Case ◽  
Environmental Sciences ◽  
Wide Range

This thoroughly updated seventh edition is a comprehensive, clearly written, and practical textbook that includes information on both occupational health and environmental health, providing the necessary foundation for recognizing and preventing work-related and environmentally induced diseases and injuries. National and international experts share their knowledge and practical experience in addressing a wide range of issues and evolving challenges in their fields. A multidisciplinary approach makes this an ideal textbook for students and practitioners in public health, occupational and environmental medicine, occupational health nursing, epidemiology, toxicology, occupational and environmental hygiene, safety, ergonomics, environmental sciences, and other fields. Comprehensive coverage provides a clear understanding of occupational and environmental health and its relationships to public health, environmental sciences, and government policy. Practical case studies demonstrate how to apply the basic principles of occupational and environmental health to real-world challenges. Numerous tables, graphs, and photographs reinforce key concepts. Annotated Further Reading sections at the end of chapters provide avenues for obtaining further infomation. This new edition of the book is thoroughly updated and also contains new chapters on climate change, children’s environmental health, liver disorders, kidney disorders, and a global perspective on occupational health and safety.

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