Clinical Reviews in Allergy & Immunology最新文献

Tissue-resident memory T (TRM) cells constitute a distinct subset within the memory T cell population, serving as the vanguard against invading pathogens and antigens in peripheral non-lymphoid tissues, including the respiratory tract, intestines, and skin. Notably, TRM cells adapt to the specific microenvironment of each tissue, predominantly maintaining a sessile state with distinctive phenotypic and functional attributes. Their role is to ensure continuous immunological surveillance and protection. Recent findings have highlighted the pivotal contribution of TRM cells to the modulation of adaptive immune responses in allergic disorders such as allergic rhinitis, asthma, and dermatitis. A comprehensive understanding of the involvement of TRM cells in allergic diseases bears profound implications for allergy prevention and treatment. This review comprehensively explores the phenotypic characteristics, developmental mechanisms, and functional roles of TRM cells, focusing on their intricate relationship with allergic diseases.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an increased risk of cardiovascular events, due to the complex interplay between traditional and disease-related risk factors. Chronic inflammation and persistent disease activity are the key determinants of this risk, but despite great improvement in the disease management and prognosis, cardiovascular events are still the main cause of morbidity and mortality in RA cohorts¹. In the last decades, the advent of new biological and targeted-synthetic DMARDs was accompanied by an improvement in disease activity control, but the role of each class of drugs on CVD risk is still a matter a debate. Since their approval for RA treatment, tumor necrosis factor alpha (TNFα) inhibitors have been widely investigated to better understand their effects on cardiovascular outcomes. The hypothesis that the reduction of chronic inflammation with any treatment may reduce the cardiovascular risk has been recently confuted by the direct comparison of TNFα-inhibitors and JAK inhibitors in patients with RA and coexisting risk factors for cardiovascular disease. The aim of this literature review is to add to the available evidence to analyze the relationship between TNFα-inhibitors and CVD risk in patients with RA and also provide some clinical scenarios to better explain the treatment dilemmas. In particular, while data on major cardiovascular events and thromboembolism seem consistent with an inflammation-mediated benefit with TNFα-inhibitors, there remain concerns about the use of this class of bDMARDs in patients with chronic heart failure.

Abstract

Recent advances in medical genetics elucidated the background of diseases characterized by superficial dermal and epidermal inflammation with resultant aberrant keratosis. This led to introducing the term autoinflammatory keratinization diseases encompassing entities in which monogenic mutations cause spontaneous activation of the innate immunity and subsequent disruption of the keratinization process. Originally, autoinflammatory keratinization diseases were attributed to pathogenic variants of CARD14 (generalized pustular psoriasis with concomitant psoriasis vulgaris, palmoplantar pustulosis, type V pityriasis rubra pilaris), IL36RN (generalized pustular psoriasis without concomitant psoriasis vulgaris, impetigo herpetiformis, acrodermatitis continua of Hallopeau), NLRP1 (familial forms of keratosis lichenoides chronica), and genes of the mevalonate pathway, i.e., MVK, PMVK, MVD, and FDPS (porokeratosis). Since then, endotypes underlying novel entities matching the concept of autoinflammatory keratinization diseases have been discovered (mutations of JAK1, POMP, and EGFR). This review describes the concept and pathophysiology of autoinflammatory keratinization diseases and outlines the characteristic clinical features of the associated entities. Furthermore, a novel term for NLRP1-associated autoinflammatory disease with epithelial dyskeratosis (NADED) describing the spectrum of autoinflammatory keratinization diseases secondary to NLRP1 mutations is proposed.

Gastrointestinal adverse events are common during oral immunotherapy (OIT) for food allergy and range from immediate IgE-mediated reactions to non-anaphylactic clinical presentations. This review aims to summarize recent findings on non-anaphylactic eosinophil-associated gastrointestinal adverse events during OIT. Two clinical presentations of non-anaphylactic eosinophil-associated gastrointestinal adverse events during OIT are identified, each with a different paradigm for treatment, and distinguished by their time of onset. In the first clinical entity, characterized by its onset early in the course of treatment, patients present with abdominal pain, nausea, and/or vomiting. The symptoms become evident typically within weeks to months of starting OIT. These symptoms, however, are not temporally related to the time of dose administration, as in the case of immediate IgE-mediated anaphylactic reactions. While esophageal biopsies, when performed, can demonstrate eosinophilic esophagitis (EoE), baseline esophageal eosinophilia has also been observed in food allergic patients prior to OIT. A potential non-invasive biomarker, the peripheral absolute eosinophil count (AEC), often rises during these reactions and subsides after dose reduction and subsequent resolution of symptoms. OIT can usually then be resumed, albeit at a slower pace, without a recurrence of symptoms. Risk factors for development of symptoms early during OIT include a high starting dose and a baseline AEC of greater than 600. The second, and much less frequently encountered, non-anaphylactic gastrointestinal adverse event related to OIT, presents months to years after initiating OIT. In this latter group, patients present with the classical clinical symptoms and endoscopic findings of EoE. In contrast to the acute onset group, peripheral eosinophilia is usually not observed in these cases. This OIT-associated EoE has shown good response to standard EoE treatment approaches of proton pump inhibitors or swallowed steroids. Most patients with eosinophil-associated adverse reactions are able to continue OIT and remain desensitized. Treatment approaches depend on the specific subtype of these reactions and relate to the stages of OIT treatment.

Chronic rhinosinusitis (CRS) is a highly heterogeneous disease characterized by inflammation in the nasal and sinus mucosa. The CRS phenotypes, based on the presence or absence of nasal polyps, are known as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). However, this classification has limitations in fully capturing the mechanisms and clinical manifestations of CRS. To address the heterogeneity of CRS, there has been a growing focus on classifying the condition into distinct endotypes. Endotype classification involves grouping patients based on specific molecular, immunological, and clinical characteristics, allowing for more personalized and targeted treatment approaches.This review delves into the current state of endotype classifications for CRS. It explores the role of geographic factors, microbiome, and subphenotype in shaping different endotypes. Additionally, the review examines how various clinical features are associated with specific endotypes, providing valuable insights into tailoring treatment options for better outcomes and transitions between different endotypes.Overall, this review offers a comprehensive and up-to-date perspective on the intricate realm of CRS endotype classifications. By unraveling the molecular and clinical intricacies, this review lays the foundation for more precise, effective, and individualized treatment strategies in the management of CRS.

Sulfonamides, which are drugs commonly prescribed in hospital and outpatient settings, have historically been associated with a high incidence of hypersensitivity reactions. It is believed that there is an increased risk of cross-reactions with other drugs that contain this functional group in their structure. However, it has not been conclusively established that the sulfonamide group is the sole cause of hypersensitivity reactions, as non-antibiotic sulfonamides do not share the same accessory groups with antibiotic sulfonamides. Therefore, cross-reactivity between different types of sulfonamides and sulfonamide-type antibiotics is not clearly demonstrated, and allergic reactions may involve other mechanisms. Misinformation about this topic can lead to inappropriate use of alternative antibiotics with lower efficacy or higher adverse effects, contributing to antibiotic resistance. It is crucial to individualize and monitor patients with a history of allergies to sulfonamide-type antibiotics when introducing a new drug containing sulfa and manage any adverse reactions promptly. Desensitization protocols may be a viable option for patients who specifically benefit from these antibiotics, particularly those who are immunosuppressed. This article provides a descriptive bibliographic review to update information on sulfa allergy, its prevalence, management, and recommendations to prevent such reactions and optimize pharmacotherapy, without underusing these drugs.

Hereditary angioedema (HAE) and acquired C1-inhibitor deficiency (AAE-C1-INH) are orphan diseases. Berotralstat is a recently licensed long-term prophylaxis (LTP) and the first oral therapy for HAE patients. No approved therapies exist for AAE-C1-INH patients. This study is the first to report real-world clinical data of patients with AAE-C1-INH and HAE who received Berotralstat. All patients treated with Berotralstat were included in this retrospective, bi-centric study. Data was collected from patients' attack calendars and the angioedema quality of life (AE-QoL) and angioedema control test (AECT) questionnaires before treatment, and at 3, 6, and 12 months after treatment and was then analyzed. Twelve patients were included, 3 patients with AAE-C1-INH, 7 patients with HAE type I, and 2 patients with HAE-nC1-INH. One patient (HAE I) quit treatment. Berotralstat was associated with fewer attacks in all groups. After 6 months of treatment, a median decrease of attacks per month was noted for HAE type I patients (3.3 to 1.5) and AAE-C1-INH patients (2.3 to 1.0). No aerodigestive attacks were noted for AAE-C1-INH patients. For HAE-nC1-INH patients, a mean decrease from 3.8 to 1.0 was noted (3 months). For HAE I patients, the total AE-QoL lowered a mean of 24.1 points after 6 months, for HAE-nC1-HAE patients 8.0 points, and for AAE-C1-INH patients 13.7 points. AECT scores increased for HAE I patients (mean: 7.1), HAE-nC1-INH patients (9.0), and AAE-C1-INH patients (4.2) after 6 months. Patients with HAE, HAE-nC1-INH, and AAE-C1-INH treated with Berotralstat showed reduced angioedema attacks and improved AE-QoL and AECT scores.

Bullous pemphigoid is one of the most common autoimmune bullous diseases occurring primarily in the elderly. Pathogenic autoantibodies against BP180 and BP230 at the dermal-epidermal junction cause subepidermal blisters, erosions, and intense pruritus, all of which adversely affect the patients' quality of life and may increase their morbidity and mortality. Current systemic treatment options for bullous pemphigoid are limited to corticosteroids and immunosuppressants, which can have substantial side effects on these vulnerable patients that even exceed their therapeutic benefits. Therefore, more precisely, targeting therapies to the pathogenic cells and molecules in bullous pemphigoid is an urgent issue. In this review, we describe the pathophysiology of bullous pemphigoid, focusing on autoantibodies, complements, eosinophils, neutrophils, proteases, and the T helper 2 and 17 axes since they are crucial in promoting proinflammatory environments. We also highlight the emerging therapeutic targets for bullous pemphigoid and their latest discoveries in clinical trials or experimental studies. Further well-designed studies are required to establish the efficacy and safety of these prospective therapeutic options.

The human gastrointestinal tract houses an enormous microbial ecosystem. Recent studies have shown that the gut microbiota plays significant physiological roles and maintains immune homeostasis in the human body. Dysbiosis, an imbalanced gut microbiome, can be associated with various disease states, as observed in infectious diseases, inflammatory diseases, autoimmune diseases, and cancer. Modulation of the gut microbiome has become a therapeutic target in treating these disorders. Fecal microbiota transplantation (FMT) from a healthy donor restores the normal gut microbiota homeostasis in the diseased host. Ample evidence has demonstrated the efficacy of FMT in recurrent Clostridioides difficile infection (rCDI). The application of FMT in other human diseases is gaining attention. This review aims to increase our understanding of the mechanisms of FMT and its efficacies in human diseases. We discuss the application, route of administration, limitations, safety, efficacies, and suggested mechanisms of FMT in rCDI, autoimmune diseases, and cancer. Finally, we address the future perspectives of FMT in human medicine.

Air pollution is associated with multiple health problems worldwide, contributing to increased morbidity and mortality. Atopic dermatitis (AD) is a common allergic disease, and increasing evidence has revealed a role of air pollution in the development of atopic dermatitis. Air pollutants are derived from several sources, including harmful gases such as nitrogen dioxide (NO₂), sulfur dioxide (SO₂), and carbon monoxide (CO), as well as particulate matter (PM) of various sizes, and bioaerosols. Possible mechanisms linking air pollution to atopic dermatitis include damage to the skin barrier through oxidative stress, increased water loss, physicochemical injury, and an effect on skin microflora. Furthermore, oxidative stress triggers immune dysregulation, leading to enhanced sensitization to allergens. There have been multiple studies focusing on the association between various types of air pollutants and atopic dermatitis. Since there are many confounders in the current research, such as climate, synergistic effects of mixed pollutants, and diversity of study population, it is not surprising that inconsistencies exist between different studies regarding AD and air pollution. Still, it is generally accepted that air pollution is a risk factor for AD. Future studies should focus on how air pollution leads to AD as well as effective intervention measures.