China
Africa
Explore chapters and articles related to this topic
Vasculitides
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Ivy M. Obonyo, Virginia A. Jones, Kayla A. Clark, Maria M. Tsoukas
Laboratory studies: Histologic study will show eosinophilia in the tissues (>10%), disseminated small vessel vasculitis, extravascular granulomatous change, and fibrinoid necrosis (Figure 13.11). When active, C-reactive protein (CRP) and ESR may be elevated. IgE is also elevated in patients with EGPA, but this is not specific. Elevated IgG4 levels are more specific and should be measured. Up to 90% of EGPA patients are positive for p-ANCA, but this is not diagnostic. Eotaxin-3, a chemokine that attracts eosinophils, is both sensitive and specific to EGPA when active.
Food allergies and eosinophilic gastrointestinal diseases
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Cathryn Nagler, Glenn T. Furuta
The heritability of the predisposition to allergic disease suggests a genetic basis, but susceptibility genes for food allergy are as yet largely unidentified. Common (atopy) and unique (food allergy) genetic risk factors may contribute to allergic responses to food. Genome-wide association studies have identified intriguing candidates that may provide new insight into disease pathogenesis, particularly for EoE. The first genome-wide association study for EoE showed that eotaxin-3, a prominent eosinophil-recruiting chemokine, was the most upregulated gene in the esophageal epithelia of children with EoE. Further work has identified an epithelial cluster of EoE-associated genes, including filaggrin, an epidermal barrier protective protein. Loss-of-function variants in filaggrin are associated with atopic dermatitis in some patients. This finding is particularly relevant to EoE, since the esophagus (like the skin) is lined by squamous epithelium. If epithelial barrier function is impaired, as may occur with loss of filaggrin function, luminal allergens could enter the lamina propria and initiate an allergic response. Finally, variants in the epithelial cell alarmin TSLP have been implicated in susceptibility to EoE. The disease model that emerges involves a series of genes related to epithelial barrier defects, eosinophil chemotaxis, and predisposition to a TH2 phenotype (Figure 35.6).
Pharmaceuticals: Some General Aspects
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
The three latest orphan medical products designated by the EMA early 2018 (EMA, 2018b) via accelerated assessment after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended marketing approval are Crysvita (burosumab), Prevymis (letermovir), and Jorveza (budesonide). The active substance of Crysvita (Kyowa Hakko Kirin Co. Ltd., Kyowa Kirin International PLC and Ultragenyx Pharmaceutical) is burosumab, a recombinant fully humanized monoclonal IgG1 antibody that binds to and inhibits the activity of fibroblast growth factor 23. The drug is indicated for the treatment of X-linked hypophosphataemia (XLH, a chronic progressive musculoskeletal disorder) with radiographic evidence of bone disease in children 1 year of age and older. The antiviral agent Prevymis (letermovir), a non-nucleosidic, inhibitor is used for prophylaxis of cytomegalovirus (CMV) infection and disease in adults and acts by inhibiting the human CMV viral terminase by a mechanism that remains to be elucidated (Ligat et al., 2018). CMV may cause life-threatening infections in immuno-compromised patients and serious congenital malformations. Prevymis is marketed by Merck & Co., Inc. (or Merck Sharp & Dohme (kurz MSD)) and was developed by AiCuris up to the clinical phase 2b. AiCuris received from Merck €30 million in addition to €105 million that became due after approval of Prevymis by the FDA in November 2017. Jorveza (with the glucocorticosteroid budesonide), marketed by Dr. Falk Pharma GmbH, Germany, is a medicine used to treat adults with the rare inflammatory disease eosinophilic esophagitis, a designation stemming from the fact that in the tissue of the esophagus in patients with this disease numbers of white blood cells called eosinophils are very high. Budesonide acts by preventing antigen-stimulated secretion of proinflammatory signal molecules such as thymic stromal lymphopoeitin (TSLP, a protein belonging to the cytokine family and produced mainly by non-hematopoietic cells (its expression is linked not only to eosinophilic esophagitis but also to other diseases, e.g., asthma, inflammatory arthritis, atopic dermatitis, etc.), interleukin-13 (the IL-13 protein is associated primarily with the induction of airway diseases), and eotaxin-3 (or chemokine (C-C motif) ligand 26 (CCL26) in the esophageal epithelium. Eotaxin-3 is a small cytokine belonging to the CC chemokine family and chemotactic for eosinophils (and basophils); for the regulatory role of this human chemokine in connection with attracting eosinophils and basophils, see Petkovic et al. (2004).
What place will tezepelumab hold in the treatment paradigm in chronic rhinosinusitis?
Published in Expert Review of Clinical Immunology, 2023
Valentin Favier, Jérémy Charriot, Louis Crampette, Arnaud Bourdin, Engi Ahmed
T2-polyps have been shown to be mainly composed of monotonous p63-expressing basal cells associated to a loss of the other classical epithelial subtypes notably secretory and ciliated cells [5]. Single cell RNA sequencing of NP highlighted an impairment in the differentiation ability of basal cells that accumulate at this early ontogenic state (‘basal cell hyperplasia’). Basal cells in eosinophilic CRSwNP showed the highest expression of proinflammatory genes, especially those linked to type 2 inflammation, including the nitric oxide synthase (NOS2), that may be linked to high exhaled nitric oxide (FeNO) levels, TSLP, IL-4/13-induced genes, chemokines such as eotaxin-3, CLC (Charcot-Leyden crystal), and protease inhibitors such as cystatins. Eotaxin 3 is a potent chemoattractant for eosinophils through the binding to the cell surface chemokine receptor CCR3.
Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study
Published in OncoImmunology, 2021
Wencheng Zhang, Cihui Yan, Tian Zhang, Xi Chen, Jie Dong, Jingjing Zhao, Dong Han, Jun Wang, Gang Zhao, Fuliang Cao, Dejun Zhou, Hongjing Jiang, Peng Tang, Lujun Zhao, Zhiyong Yuan, Quanren Wang, Ping Wang, Qingsong Pang
We found both high level of IL-27 and high level of IL-15 in peripheral blood were associated with better survival. The cytokine IL-15 has a key role in promoting survival, proliferation and activation of natural killer and T cells.46,47 IL-27 had double ways in antitumor efficacy.48 Both IL-15 and IL-27 contribute to maintain homeostasis of memory T cells.49,50 As far, their association with survival in checkpoint blockade with or without conventional anti-tumor therapies was little known. Eotaxin-3 was the most highly induced gene in eosinophilic esophagitis patients compared with its expression level in healthy individuals.51 Eotaxin-3 had two receptors CCR3 and CX3CR1. Eotaxin-3 expressed by hepatocellular carcinoma cells could recruit CX3CR1+ MDSCs to the tumor tissue.52 IL-22 is exclusively produced by immune cells. Increased numbers of intratumoral and peripheral IL-22 secreting cells have been reported in lung, gastric, colorectal, pancreatic and hepatocellular carcinomas and enhanced tumor progression.53 Neither Eotaxin-3 nor IL-22 was reported in esophageal cancer. Our findings in peripheral blood illustrate the important role of systemic immune response in antitumour treatment and provide convenient biomarkers for patient selection. Lastly, for patients with CCND1/FGF19/FGF4 amplification, combining targeted therapy might improve treatment efficiency, and deserves further study.
Immunohistochemical markers for eosinophilic esophagitis
Published in Scandinavian Journal of Gastroenterology, 2020
Katarzyna Zdanowicz, Magdalena Kucharska, Joanna Reszec, Dariusz Marek Lebensztejn, Urszula Daniluk
Eotaxin-3 (also known as CCL26) is a chemokine, that signals through the C-C chemokine receptor type 3 (CCR3) and recruits eosinophils and mast cell into the esophagus tissue. Local production of epithelial eotaxin-3 is stimulated by T-helper cell type 2 (Th2) cytokines (IL-4 and IL-13). Eotaxin-3 staining has also been observed in the esophageal fibroblasts suggesting that eotaxin-3 may be involved in fibrosis [16]. In EoE, an increased expression of eotaxin-3 in cell nuclei and squamous cells cytoplasm and eotaxin mRNA has been observed compared to GERD [17,18]. Expression of eotaxin-3 may also be useful in the differential diagnosis of EoE and eosinophilic esophageal myositis (EoEM). An increase in the number of eotaxin-3-positive epithelial cells was observed in subjects with EoE, in contrast to EoEM patients with eotaxin-3-positive myocytes and vascular endothelial cells in the esophageal muscle layer [19]. Among EoE patients, no significant differences in eotaxin-3 detection were observed between atopic and non-atopic individuals [20]. Furthermore, omeprazole reduced cytokine-stimulated expression of eotaxin-3, so this finding could explain the effect of PPI on symptom improvement and histological remission in EoE patients [21]. Detection of eotaxin-3 expression in the esophagus may be useful in the differential diagnosis of EoE and EoEM, but also in the choice of the appropriate treatment. Patients with EoE and positive eotaxin-3 staining, should be treated with IPP to reduce eotaxin-3 expression and prevent esophageal tissue fibrosis and improve treatment effects. The effectiveness of such proposed diagnostic-therapeutic option should be confirmed in further studies.