Dysregulated specific IgE production to bystander foods in children with peanut allergy but not egg allergy.

Background: Food specific immunoglobulin E (sIgE) levels are associated with the development of allergic responses and are used in the clinical evaluation of food allergy. Food sIgG4 levels have been associated with tolerance or clinical nonresponsiveness, particularly in interventional studies.

Objective: We aimed to characterize food-specific antibody responses and compare responses with different foods in food allergy.

Retinoic acid promotes fibrinolysis and may regulate polyp formation.

Background: Patients with aspirin-exacerbated respiratory disease (AERD) regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary for maintaining epithelial function and well-known inducers of tPA in endothelial cells.

Studies on activation and regulation of the coagulation cascade in chronic rhinosinusitis with nasal polyps.

Background: Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). More information is needed concerning mechanisms of coagulation in CRSwNP.

Objective: We investigated the mechanisms as well as the initiation and regulation of coagulation cascade activation in CRS.

Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps.

Background: Polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells and fibrin deposition. Anti-phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS).

Objective: To compare APA levels (anti-cardiolipin, anti-phosphatidylethanolamine (anti-PE), and anti-β -glycoprotein (anti-B2GP)) in nasal polyp (NP) tissue with tissue from control and CRS without nasal polyp (CRSsNP) patients, we tested whether NP antibodies affect coagulation, and correlate APAs with anti-dsDNA IgG and markers of coagulation.

Studies of the role of basophils in aspirin-exacerbated respiratory disease pathogenesis.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type 2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear.

Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD.

Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated.

Increased thrombin-activatable fibrinolysis inhibitor levels in patients with chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease subdivided based on the presence or absence of nasal polyps (NPs). Histologic features of chronic rhinosinusitis with nasal polyps (CRSwNP) include inflammatory cell infiltration and excessive fibrin deposition in NPs. Thrombin-activatable fibrinolysis inhibitor (TAFI) is an enzyme that plays an antifibrinolytic role in the body.

TNF induces production of type 2 cytokines in human group 2 innate lymphoid cells.

TNF receptor II is expressed on ILC2s and TNF is able to induce production of type 2 cytokines in human ILC2s. TNF may play a role in causing or amplifying type 2 immunity contributing to health and disease.

Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation in the nose and paranasal sinuses. Inflammation in CRS is also heterogeneous and is mainly characterized by type 2 (T2) inflammation, but subsets of patients show type 1 (T1) and type 3 (T3) inflammation. Whether inflammatory endotypes are associated with clinical phenotypes has yet to be explored in detail.

Oligoclonal immunoglobulin repertoire in biliary remnants of biliary atresia.

Biliary atresia (BA) is a neonatal cholestatic liver disease that is the leading cause of pediatric liver transplantation, however, the mechanism of disease remains unknown. There are two major forms of BA: isolated BA (iBA) comprises the majority of cases and is thought to result from an aberrant immune response to an environmental trigger, whereas syndromic BA (BASM) has associated malformations and is thought to arise from a congenital insult. To determine whether B cells in BA biliary remnants are antigen driven, we examined the immunoglobulin (Ig) repertoire of diseased tissue from each BA group.

Pathogenic and protective roles of B cells and antibodies in patients with chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nose and sinuses that affects up to 12% of the population in Europe and the United States. This complex disease is likely driven by multiple environmental, genetic, and inflammatory mechanisms, and recent studies suggest that B cells might play a critical role in disease pathogenesis. B cells and their antibodies have undisputed roles in health and disease within the airway mucosae.

Mast Cell Interactions and Crosstalk in Regulating Allergic Inflammation.

Purpose Of Review: This review summarizes recent findings on mast cell biology with a focus on IgE-independent roles of mast cells in regulating allergic responses.

Recent Findings: Recent studies have described novel mast cell-derived molecules, both secreted and membrane-bound, that facilitate cross-talk with a variety of immune effector cells to mediate type 2 inflammatory responses. Mast cells are complex and dynamic cells that are persistent in allergy and are capable of providing signals that lead to the initiation and persistence of allergic mechanisms.

Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis.

Background: IgD is an enigmatic antibody isotype best known when coexpressed with IgM on naive B cells. However, increased soluble IgD (sIgD) levels and increased IgDIgM B-cell populations have been described in the human upper respiratory mucosa.

Objective: We assessed whether levels of sIgD and IgD B cell counts are altered in nasal tissue from patients with chronic rhinosinusitis (CRS).

Acquired Immunity in Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a prevalent disease that is associated with significant costs and quality of life impairments. Currently, patients are classified into subgroups based on clinical characteristics, most often the presence or absence of nasal polyps. However, despite medical and surgical treatment, many of these patients continue to have symptoms.

Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines. However, the presence of various types of ILC in CRS is poorly understood.

Superior turbinate eosinophilia correlates with olfactory deficit in chronic rhinosinusitis patients.

Objective: To evaluate if molecular markers of eosinophilia in olfactory-enriched mucosa are associated with olfactory dysfunction.

Study Design: Cross-sectional study of tissue biopsies from 99 patients, and an additional 30 patients who underwent prospective olfactory testing prior to sinonasal procedures.

Methods: Tissue biopsies were processed for analysis of inflammatory markers using quantitative real time polymerase chain reaction (qRT-PCR).

Clinical Characteristics of Patients with Chronic Rhinosinusitis with Nasal Polyps, Asthma, and Aspirin-Exacerbated Respiratory Disease.

Background: Aspirin-exacerbated respiratory disease (AERD) comprises the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to inhibitors of the cyclooxygenase-1 (COX-1) enzyme. The prevalence of AERD remains unclear, and few studies have compared the clinical characteristics of patients with AERD to those with CRSwNP alone, asthma alone, or both CRSwNP and asthma.

Objective: To determine the prevalence of AERD within a tertiary care setting, and to identify unique clinical features that could distinguish these patients from those with both CRSwNP and asthma or with CRSwNP alone.

Microparticles in nasal lavage fluids in chronic rhinosinusitis: Potential biomarkers for diagnosis of aspirin-exacerbated respiratory disease.

Background: Microparticles (MPs) are submicron-sized shed membrane vesicles released from activated or injured cells and are detectable by flow cytometry. MP levels have been used as biomarkers to evaluate cell injury or activation in patients with pathological conditions.

Objective: We sought to compare MP types and levels in nasal lavage fluids (NLFs) from controls and patients with chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD).

Discordant frequencies of tissue-resident and circulating CD180-negative B cells in chronic rhinosinusitis.

Background: The unconventional toll-like receptor (TLR) CD180 is implicated in chronic inflammatory diseases; however, its role in chronic rhinosinusitis (CRS) has yet to be investigated. Here we study the expression of CD180, its homologue TLR4 and myeloid differentiation factor 1 (MD1) on mucosal and systemic immune cell populations in relation to serum immunoglobulin G (IgG) levels.

Methods: A total of 70 patients were recruited to the study.