Clinical reviews in allergy & immunology
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Clin Rev Allergy Immunol · Feb 2021
ReviewImmunometabolic Pathways and Its Therapeutic Implication in Autoimmune Diseases.
Autoimmune diseases (AIDs) are characterized with aberrant immune responses and their respective signaling pathways controlling cell differentiation, death, and survival. Cell metabolism is also an indispensable biochemical process that provides the very fundamental energy and materials. Accumulating evidences implicate that metabolism pathways have critical roles in determining the function of different immune subsets. ⋯ Here, in this review, we summarize the metabolic features of immune cells in AIDs and also the individual function of immunometabolism pathways, including glucose metabolism and tricarboxylic acid (TCA) cycle, in the setting of AIDs, mainly focusing on the potential targets for intervention. We also review studies that explore the intervention strategies targeting key molecules of metabolic pathways, such as mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and hypoxia-inducible factor 1a (HIF1a), in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The highlight of this review is to provide a comprehensive summary of the status quo of immunometabolism studies in AIDs and the potential translatable drug targets.
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Clin Rev Allergy Immunol · Oct 2020
ReviewThe Current State of Biologic Therapies for Treatment of Refractory Asthma.
Asthma is a heterogeneous disease, with the immune processes behind the chronic inflammation underlying this disorder differing between the various identified asthma endotypes. In addition to heterogeneity in underlying disease pathophysiology, asthmatics fall across a broad spectrum of disease severity and can vary greatly in their response to convention asthma therapies. A small percentage of patients with severe persistent asthma will remain uncontrolled despite treatment with high-dose inhaled corticosteroids and a long-acting beta-agonist. ⋯ The optimal biologic for treatment of severe asthma varies from patient to patient, depending on the underlying pathophysiology of the patient's disease. For each of these medications, there are certain biomarkers that can help predict whether a patient is likely to respond favorably to the medication. This review will discuss the currently approved biologics for severe persistent asthma, including their indications, efficacy and side effects.
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Over the last few decades, advances in our understanding of microbial ecology have allowed us to appreciate the important role of microbial communities in maintaining human health. While much of this research has focused on gut microbes, microbial communities in other body sites and from the environment are increasingly recognized in human disease. Here, we discuss recent advances in our understanding of host-microbiota interactions in the development and manifestation of asthma focusing on three distinct microbial compartments. ⋯ The mechanisms by which gut microbial communities influence lung immune responses and physiology, the "gut-lung axis," are still being defined but include the altered differentiation of immune cell populations important in asthma and the local production of metabolites that affect distal sites. Together, these findings suggest an intimate association of microbial communities with host immune development and the development of allergic airway inflammation. Improved understanding of these relationships raises the possibility of microbiota-directed therapies to improve or prevent asthma.
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Food allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the immune system, causing a T helper 2 response which results in IgE binding to Fcε receptors on effector cells like mast cells and basophils. The activation of these cells causes release of histamine and other preformed mediators, and rapid symptom onset, in contrast with non-IgE-mediated food allergy which is more delayed in onset. ⋯ Guidelines have changed recently to include early introduction of peanuts at 4-6 months of life. Early introduction is recommended to prevent the development of peanut allergy. Future treatments for IgE-mediated food allergy evaluated in clinical trials include epicutaneous, sublingual, and oral immunotherapy.
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Clin Rev Allergy Immunol · Oct 2019
ReviewFood Protein-Induced Enterocolitis Syndrome: a Comprehensive Review.
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that has been well-characterized clinically, yet it is still poorly understood. Acute FPIES is characterized by vomiting 1-4 h and/or diarrhea within 24 h after ingestion of a culprit food. Chronic FPIES is the result of chronic exposure to an offending food that can result in chronic watery diarrhea, intermittent vomiting, and failure to thrive. ⋯ Acute management during reactions includes IV hydration, anti-emetics, and IV corticosteroids. Reaction prevention strategies include strict food avoidance until the physician deems a food reintroduction challenge clinically appropriate. Future efforts in FPIES research should be aimed at elucidating the underlying disease mechanisms and possible treatment targets.