Introduction to immunology and immune disorders.

The body has a collection of physical barriers to prevent infection, but once these are overcome, we rely on our immune systems to protect us against a wide variety of infections. The complex mechanisms through which this is achieved are grouped into two lines of defense called the "innate" and "adaptive" immune systems. The innate immune system provides a rapid and tailored response to infection or injury often associated with inflammation.

PrP is cleaved from the surface of mast cells by ADAM10 and proteases released during degranulation.

While several functions of the endogenous prion protein have been studied, the homeostatic function of prion protein is still debated. Notably, prion protein is highly expressed on mast cells, granular immune cells that regulate inflammation. When activated, mast cells shed prion protein, although the mechanism and consequences of this are not yet understood.

Effectiveness of immunoglobulin replacement therapy in preventing infections in patients with chronic obstructive pulmonary disease: a systematic review.

Purpose: Immunoglobulin replacement therapy is a standard treatment for patients with antibody production deficiencies, which is of interest in patients with chronic obstructive pulmonary disease (COPD). This systematic review, registered with PROSPERO (CRD42021281118), assessed the current literature regarding immunoglobulin replacement therapy on COPD clinical outcomes in patients with low immunoglobulin G (IgG) serum concentrations.

Methods: Literature searches conducted from inception to August 23, 2021, in databases including MEDLINE, EMBASE, and CINAHL.

German cockroach extract prevents IL-13-induced CCL26 expression in airway epithelial cells through IL-13 degradation.

Inhaled aeroallergens can directly activate airway epithelial cells (AECs). Exposure to cockroach allergens is a strong risk factor for asthma. Cockroach allergens mediate some of their effects through their serine protease activity; protease activity is also a major contributor to allergenicity.

Association of single nucleotide polymorphisms in the F2RL1 gene with clinical and inflammatory characteristics of patients with asthma.

Background: Proteinase-activated receptor 2 (PAR-2) is a G-protein coupled receptor associated with many inflammatory diseases, including asthma. We have shown an association between PAR-2 expression in peripheral blood monocytes and asthma severity as well as blood PAR-2 mRNA level and lung function. Since F2RL1 (the gene encoding PAR-2) polymorphisms affect PAR-2 expression, we hypothesize they may affect asthma severity.

Protease allergens as initiators-regulators of allergic inflammation.

Tremendous progress in the last few years has been made to explain how seemingly harmless environmental proteins from different origins can induce potent Th2-biased inflammatory responses. Convergent findings have shown the key roles of allergens displaying proteolytic activity in the initiation and progression of the allergic response. Through their propensity to activate IgE-independent inflammatory pathways, certain allergenic proteases are now considered as initiators for sensitization to themselves and to non-protease allergens.

Low immunoglobulin levels affect the course of COPD in hospitalized patients.

Background: Chronic obstructive pulmonary disease (COPD) affects up to 10% of Canadians. Patients with COPD may present with secondary humoral immunodeficiency as a result of chronic disease, poor nutrition or frequent courses of oral corticosteroids; decreased humoral immunity may predispose these patients to mucosal infections. We hypothesized that decreased serum immunoglobulin (Ig) levels was associated with the severity of an acute COPD exacerbations (AECOPD).

The CRTh2 polymorphism rs533116 G > A associates with asthma severity in older females.

Background: CRTh2 is G protein coupled receptor for prostaglandin D2 (PGD) expressed by immune cells that drive type 2 inflammation such as CD4 T cells (Th2), eosinophils and group 2 innate lymphoid cells (ILC2) as well as structural cells including smooth muscle and epithelium. CRTh2-expressing cells are increased in the blood and airways of asthmatics and severe asthma is characterized by increased activity of the PGD-CRTh2 pathway. The single nucleotide polymorphism (SNP) rs533116 G > A is associated with development of asthma and increased Th2 cell differentiation.

Challenges in severe asthma: Do we need new drugs or new biomarkers?

Severe asthma is a complex, heterogenous airway condition. There have been significant advances in severe asthma management in the past decade using monoclonal antibody therapies that target the inflammatory component of the disease. Patient selection has been paramount for the success of these biologicals, leading to significant interest in biomarkers to guide treatment.

Dual activation of estrogen receptor alpha and glucocorticoid receptor upregulate CRTh2-mediated type 2 inflammation; mechanism driving asthma severity in women?

Background: Type 2-high asthma is characterized by elevated levels of circulating Th2 cells and eosinophils, cells that express chemoattractant-homologous receptor expressed on Th2 cells (CRTh2). Severe asthma is more common in women than men; however, the underlying mechanism(s) remain elusive. Here we examined whether the relationship between severe asthma and type 2 inflammation differs by sex and if estrogen influences Th2 cell response to glucocorticoid (GC).

Protease-activated receptor-2: Role in asthma pathogenesis and utility as a biomarker of disease severity.

PAR, a receptor activated by serine proteases, has primarily pro-inflammatory roles in the airways and may play a role in asthma pathogenesis. PAR exerts its effects in the lungs through activation of a variety of airway cells, but also activation of circulating immune cells. There is evidence that PAR expression increases in asthma and other inflammatory diseases, although the regulation of PAR expression is not fully understood.

Eosinophilic Asthma, Phenotypes-Endotypes and Current Biomarkers of Choice.

Asthma phenotyping and endotyping are constantly evolving. Currently, several biologic agents have been developed towards a personalized approach to asthma management. This review will focus on different eosinophilic phenotypes and Th2-associated endotypes with eosinophilic inflammation.

What are the respiratory health research priorities in Alberta, Canada? A stakeholder consultation.

Objective: The Respiratory Health Strategic Clinical Network (RHSCN) was launched to facilitate respiratory and sleep health through implementation of innovative, patient-centred, evidence-informed coordinated services in Alberta. In collaboration with project partners, the RHSCN aimed to determine the respiratory research priorities for Alberta.

Design: The four phases of this research prioritisation project were (1) identifying research questions from stakeholders, (2) determining which research questions had been answered in existing literature, (3) prioritising unanswered questions and (4) finalising the priorities through an inperson workshop.

Peripheral blood intermediate monocyte protease-activated receptor-2 expression increases during asthma exacerbations and after inhalation allergen challenge.

Background: Myeloid cells, especially dendritic cells and macrophages, play important roles in asthma pathophysiology. Monocytes (Mo) and macrophages express protease-activated receptor-2 (PAR-2), a proinflammatory serine protease receptor implicated in the pathophysiology of allergic airway inflammation. We have revealed that patients with severe asthma and those with a history of frequent asthma exacerbations exhibit increased PAR-2 expression on peripheral blood monocytes.

Developments in asthma incidence and prevalence in Alberta between 1995 and 2015.

Background: Asthma is a chronic respiratory disease characterized by reversible bronchoconstriction and airway inflammation. According to Statistics Canada in 2014, 8.1% of Canadians aged 12 and older reported having asthma diagnosed by a health care professional.

Th2 cell markers in peripheral blood increase during an acute asthma exacerbation.

Background: Allergic asthma is characterized by type 2 inflammation. We have shown the presence of increased type 2 inflammation in patients with severe asthma and those with frequent exacerbations. However, it is not known whether increased type 2 inflammation drives asthma exacerbations.

Elevated Circulating Th2 Cells in Women With Asthma and Psychological Morbidity: A New Asthma Endotype?

Purpose: Psychological stress shifts the immune system toward the production of T-helper (Th)-2-mediated cytokines and eosinophilia, increases the risks for both asthma and depression, and can precipitate asthma exacerbations. Th2-mediated inflammation is a characteristic of allergic asthma. We have shown that the levels of CD4 Th2 cells in the peripheral blood of patients with asthma are associated with severity and/or control of the disease.

AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management.

Our current recommendations for diagnosing and treating primary mast cell (MC) activation syndrome make use of the latest studies and consensus guidelines for clinically recognizing systemic anaphylaxis in real time, regardless of whether allergen-triggered or other pathways are involved; our current understanding of the biomarkers secreted by activated MCs that best discriminate this disorder from other conditions; and the therapeutic drugs that might selectively affect those mediators or MCs themselves. Finding familial or somatic mutations of genes that cause MCs to be hyperactivatable would extend our diagnostic tools and potentially indicate new therapeutic interventions, targeting either the mutated gene product or the associated molecular pathway. In conclusion, we trust that the clinical, laboratory, and therapeutic criteria for primary MC activation syndromes described herein will provide clinicians with practical criteria of sufficient sensitivity and specificity to diagnose most cases without overdiagnosing the disorder in patients who likely have other conditions.

Responses of human mast cells and epithelial cells following exposure to influenza A virus.

As a part of innate immune defense, the role of mast cells during viral replication has been incompletely understood. In this study, we characterized and compared the responses of the human mast cell line, LAD2, and human lung epithelial cell line, Calu-3, against three influenza A virus strains; A/PR/8/34 (H1N1), A/WS/33 (H1N1) and A/HK/8/68 (H3N2). We found that there were strain-dependent mast cell responses, and different profiles of cytokine, chemokine and antiviral gene expression between the two cell types.

Stability of peripheral blood immune markers in patients with asthma.

Background: Asthma is a complex disease with variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. We have previous suggested that PAR-2 and CRTh2 expression on specific peripheral blood cell subtypes may be biomarkers of asthma severity.

IL-2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?

Background: Glucocorticosteroids (GCs) are the main treatment for asthma as they reduce type 2 cytokine expression and induce apoptosis. Asthma severity is associated with type 2 inflammation, circulating Th2 cells and higher GC requirements.

Objective: The aim of this study was to assess whether ex vivo production of interleukin 2 (IL-2), a T-cell survival factor, associated with clinical features of asthma severity, the proportion of blood Th2 cells and Th2 cell responses to GC.