HMGB1 Carried by Small Extracellular Vesicles Potentially Plays a Role in Promoting Acquired Middle Ear Cholesteatoma.

Cholesteatoma is a specific medical condition involving the abnormal, non-cancerous growth of skin-like tissue in the middle ear, potentially leading to a collection of debris and even infections. The receptor for advanced glycation (RAGE) and its ligand, high-mobility box 1 (HMGB1), are both known to be overexpressed in cholesteatoma and play a potential role in the pathogenesis of the disease. In this study, we investigated the role of small extracellular vesicles (sEVs) in carrying HMGB1 and inducing disease-promoting effects in cholesteatoma. No significant differences in the concentration of isolated sEVs in the plasma of cholesteatoma patients (n = 17) and controls (n = 22) were found (p > 0.05); however, cholesteatoma-derived sEVs carried significantly higher levels of HMGB1 (p < 0.05). In comparison to sEVs isolated from the plasma of controls, cholesteatoma-derived sEVs significantly enhanced keratinocyte proliferation and IL-6 production (p < 0.05), potentially by engaging multiple activation pathways including MAPKp44/p42, STAT3, and the NF-κB pathway. Thus, HMGB1(+) sEVs emerge as a novel factor potentially promoting cholesteatoma progression.

Perspectives in Therapy of Chronic Rhinosinusitis.

The recent classification of chronic rhinosinusitis (CRS) focusses on investigating underlying immunopathophysiological mechanisms. Primary CRS is subdivided based on endotype dominance into type 2 (that relates mostly to the Th2 immune response with high levels of IL-5, IL-13, and IgE), or non-type 2 (that corresponds to the mix of type 1 and type 3). The treatment selection of CRS is dependent on endotype dominance. Currently, the majority of patients receive standardized care-traditional pharmacological methods including local or systemic corticosteroids, nasal irrigations or antibiotics (for a selected group of patients). If well-conducted drug therapy fails, endoscopic sinus surgery is conducted. Aspirin treatment after aspirin desensitization (ATAD) with oral aspirin is an option for the treatment in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) patients. However, in this review the focus is on the role of biological treatment-monoclonal antibodies directed through the specific type 2 immune response targets. In addition, potential targets to immunotherapy in CRS are presented. Hopefully, effective diagnostic and therapeutic solutions, tailored to the individual patient, will be widely available very soon.

Immunological Aspects of Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is related to persistent inflammation with a dysfunctional relationship between environmental agents and the host immune system. Disturbances in the functioning of the sinus mucosa lead to common clinical symptoms. The major processes involved in the pathogenesis of CRS include airway epithelial dysfunctions that are influenced by external and host-derived factors which activate multiple immunological mechanisms. The molecular bases for CRS remain unclear, although some factors commonly correspond to the disease: bacterial, fungal and viral infections, comorbidity diseases, genetic dysfunctions, and immunodeficiency. Additionally, air pollution leads increased severity of symptoms. CRS is a heterogeneous group of sinus diseases with different clinical courses and response to treatment. Immunological pathways vary depending on the endotype or genotype of the patient. The recent knowledge expansion into mechanisms underlying the pathogenesis of CRS is leading to a steadily increasing significance of precision medicine in the treatment of CRS. The purpose of this review is to summarize the current state of knowledge regarding the immunological aspects of CRS, which are essential for ensuring more effective treatment strategies.

RAGE and HMGB1 Expression in Orbital Tissue Microenvironment in Graves' Ophthalmopathy.

Graves' ophthalmopathy (GO) is a chronic autoimmune inflammatory disorder involving orbital tissues. A receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 (HMGB1) protein trigger inflammation and cell proliferation and are involved in the pathogenesis of various chronic inflammatory diseases. This study was aimed to evaluate RAGE and HMGB1 expression in GO to determine its potential clinical significance. To the best of our knowledge, this is the first study showing RAGE and HMGB1 expression in orbital tissue using immunohistochemistry. Sections of orbital adipose tissue obtained from patients diagnosed with GO (23 patients; 36 orbits) and normal controls (NC) (15 patients; 15 orbits) were analyzed by immunohistochemistry for RAGE and HMGB1 expression. Expression profiles were then correlated with clinical data of the study group. RAGE and HMGB1 expression were elevated in GO patients in comparison with NC (p = 0.001 and p = 0.02, respectively). We observed a correlation between RAGE expression and occurrence of dysthyroid optic neuropathy (DON) (p = 0.05) and levels of TSH Receptor Antibodies (TRAb) (p = 0.01). Overexpression of RAGE and HMGB1 might be associated with GO pathogenesis. In addition, RAGE and HMGB1 proteins may be considered as promising therapeutic targets, but this requires further research.

The Emerging Role of Small Extracellular Vesicles in Inflammatory Airway Diseases.

Extracellular vesicles (EVs) are produced and released by all cells and are present in all body fluids. They exist in a variety of sizes, however, small extracellular vesicles (sEVs), the EV subset with a size range from 30 to 150 nm, are of current interest. By transporting a complex cargo that includes genetic material, proteins, lipids, and signaling molecules, sEVs can alter the state of recipient cells. The role of sEVs in mediating inflammatory processes and responses of the immune system is well-documented, and adds another layer of complexity to our understanding of frequent diseases, including chronic rhinosinusitis (CRS), asthma, chronic obstructive pulmonary disease (COPD), and upper airway infections. In these diseases, two aspects of sEV biology are of particular interest: (1) sEVs might be involved in the etiopathogenesis of inflammatory airway diseases, and might emerge as attractive therapeutic targets, and (2) sEVs might be of diagnostic or prognostic relevance. The purpose of this review is to outline the biological functions of sEVs and their capacity to both augment and attenuate inflammation and immune response in the context of pathogen invasion, CRS, asthma, and COPD.

Internal Carotid Artery Aneurysm Mimicking Peritonsillar Abscess.

The extracranial internal carotid artery aneurysm (EICAA) is an uncommon arterial lesion. Patients typically present with neurologic symptoms resulting from impaired cerebral perfusion and compression symptoms of cranial nerves. Often EICAA presents as a pulsatile neck mass, which is otherwise asymptomatic. We present a case of an 84-year-old female, who was initially referred to the Emergency Department for Otolaryngology with suspected peritonsillar abscess. The patient had a history of recent upper airway infection and cardiovascular comorbidities, including hypertension and ischaemic stroke complicated by extensive neurologic deficits. Physical examination revealed a compact, nonpulsatile mass in the lateral parapharyngeal space and local erythema of the mucosa. Duplex Doppler Ultrasonography and Computed Tomography revealed an atherosclerotic aneurysm of the right internal carotid artery, measuring 63 × 55 × 88 mm, stretching from the skull base to the angle of the mandible.