Current Opinion in Allergy and Clinical Immunology最新文献

{"title":"Advances in gene therapy for inborn errors of immunity.","authors":"Lisa M Ott de Bruin, Arjan C Lankester, Frank J T Staal","doi":"10.1097/ACI.0000000000000952","DOIUrl":"10.1097/ACI.0000000000000952","url":null,"abstract":"<p><strong>Purpose of review: </strong>Provide an overview of the landmark accomplishments and state of the art of gene therapy for inborn errors of immunity (IEI).</p><p><strong>Recent findings: </strong>Three decades after the first clinical application of gene therapy for IEI, there is one market authorized product available, while for several others efficacy has been demonstrated or is currently being tested in ongoing clinical trials. Gene editing approaches using programmable nucleases are being explored preclinically and could be beneficial for genes requiring tightly regulated expression, gain-of-function mutations and dominant-negative mutations.</p><p><strong>Summary: </strong>Gene therapy by modifying autologous hematopoietic stem cells (HSCs) offers an attractive alternative to allogeneic hematopoietic stem cell transplantation (HSCT), the current standard of care to treat severe IEI. This approach does not require availability of a suitable allogeneic donor and eliminates the risk of graft versus host disease (GvHD). Gene therapy can be attempted by using a viral vector to add a copy of the therapeutic gene (viral gene addition) or by using programmable nucleases (gene editing) to precisely correct mutations, disrupt a gene or introduce an entire copy of a gene at a specific locus. However, gene therapy comes with its own challenges such as safety, therapeutic effectiveness and access. For viral gene addition, a major safety concern is vector-related insertional mutagenesis, although this has been greatly reduced with the introduction of safer vectors. For gene editing, the risk of off-site mutagenesis is a main driver behind the ongoing search for modified nucleases. For both approaches, HSCs have to be manipulated ex vivo, and doing this efficiently without losing stemness remains a challenge, especially for gene editing.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"467-477"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of allergen immunotherapy on follicular regulatory T cells.","authors":"Shi-Ran Sun,&nbsp;Yin Yao,&nbsp;Zheng Liu","doi":"10.1097/ACI.0000000000000944","DOIUrl":"10.1097/ACI.0000000000000944","url":null,"abstract":"<p><strong>Purpose of review: </strong>Emerging evidence indicating that the dysfunction of T follicular regulatory (T FR ) cells contributes to excessive immunoglobulin E (IgE) production and the development of allergic diseases. Conversely, allergen immunotherapy (AIT) modulates T FR cells abundance and function to promote immune tolerance. This review focus on the role of T FR cells in allergic diseases and AIT, with the objective of providing novel insights into the mechanisms underlying immune tolerance of AIT and proposing the potential targeting of T FR cells in the context of allergic diseases.</p><p><strong>Recent findings: </strong>Numerous studies have consistently demonstrated that T FR cells play a pivotal role in the inhibition of class switch recombination to IgE in both humans and specific murine models. This suppression is attributed to the actions of neuritin and IL-10 secreted by T FR cells, which exert direct and indirect effects on B cells. In patients with allergic rhinitis, reduced frequencies of circulating or tonsillar T FR cells have been reported, along with impaired functionality in suppressing IgE production. AIT, whether administered subcutaneously or sublingually, reinstates the frequency and functionality of T FR cells in allergic rhinitis patients, accompanied by changes of the chromatin accessibility of T FR cells. The increase in T FR cell frequency following AIT is associated with the amelioration of clinical symptoms.</p><p><strong>Summary: </strong>T FR cells exert an inhibitory effect on IgE production and demonstrate a correlation with the clinical efficacy of AIT in patients with allergic rhinitis, suggesting T FR cells hold promise as a therapeutic target for allergic diseases and potential biomarker for AIT.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"507-513"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transition of care in inborn errors of immunity.","authors":"Susan Tadros,&nbsp;Siobhan O Burns","doi":"10.1097/ACI.0000000000000948","DOIUrl":"10.1097/ACI.0000000000000948","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review outlines the principles of transition, summarizes current information about transition practices in inborn errors of immunity (IEI) and highlights general and specific considerations for transition of patients with these conditions.</p><p><strong>Recent findings: </strong>Recent surveys demonstrate the variability in access to and transition practices in IEI. Key challenges of transition in IEI from the perspective of healthcare professionals include lack of adult subspecialists, lack of access to holistic care and fragmentation of adult services. Limited research focused on IEI patient and carer perspectives highlight information gaps, poor coordination and difficulty adapting to adult healthcare structures as important challenges for smooth transition.</p><p><strong>Summary: </strong>Local policies and practices for transition in IEI are highly variable with limited assessment of outcomes or patient experience. There is a need for IEI-focused transition research and for development of national and international consensus statements to guide improved transition in IEI.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"455-460"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interstitial lung diseases in inborn errors of immunity.","authors":"Neal P Sullivan,&nbsp;Nivethietha Maniam,&nbsp;Paul J Maglione","doi":"10.1097/ACI.0000000000000951","DOIUrl":"10.1097/ACI.0000000000000951","url":null,"abstract":"<p><strong>Purpose of review: </strong>Our goal is to review current understanding of interstitial lung disease (ILD) affecting patients with inborn errors of immunity (IEI). This includes understanding how IEI might predispose to and promote development or progression of ILD as well as how our growing understanding of IEI can help shape treatment of ILD in these patients. Additionally, by examining current knowledge of ILD in IEI, we hope to identify key knowledge gaps that can become focus of future investigative efforts.</p><p><strong>Recent findings: </strong>Recent identification of novel IEI associated with ILD and the latest reports examining treatment of ILD in IEI are included. Of noted interest, are recent clinical studies of immunomodulatory therapy for ILD in common variable immunodeficiency.</p><p><strong>Summary: </strong>ILD is a frequent complication found in many IEI. This article provides a guide to identifying manifestations of ILD in IEI. We review a broad spectrum of IEI that develop ILD, including antibody deficiency and immune dysregulation disorders that promote autoimmunity and autoinflammation. This work integrates clinical information with molecular mechanisms of disease and diagnostic assessments to provide an expedient overview of a clinically relevant and expanding topic.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"500-506"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41194259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of allergen immunotherapy in children.","authors":"Kristin A Schmidlin,&nbsp;David I Bernstein","doi":"10.1097/ACI.0000000000000945","DOIUrl":"10.1097/ACI.0000000000000945","url":null,"abstract":"<p><strong>Purpose of review: </strong>The current review discusses allergen immunotherapy (AIT) safety in children.</p><p><strong>Recent findings: </strong>AIT is a well tolerated and effective treatment for pediatric allergic conditions. While mostly well tolerated, severe reactions and near fatal reactions may occur with subcutaneous immunotherapy (SCIT) once in every 160 000 visits. Sublingual immunotherapy (SLIT) is associated more with local side effects, but severe systemic reactions, including anaphylaxis, have been rarely reported. Providing informed consent, recognizing risk factors for severe systemic reactions, such as severe or uncontrolled asthma, and mitigating the risk of severe reactions are important components to improving the safety of AIT.</p><p><strong>Summary: </strong>Overall, AIT is well tolerated in children, and data suggest that the incidence of systemic reactions in children receiving SCIT is no less than mixed populations of adult and pediatric patients. SLIT carries less risk for systemic reactions, and local oral site-application reactions are usually mild and resolve within 15 days of treatment.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"514-519"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotrophic keratitis: inflammatory pathogenesis and novel therapies.","authors":"Denise Wajnsztajn,&nbsp;Lana A Faraj,&nbsp;Sara Sanchez-Tabernero,&nbsp;Abraham Solomon","doi":"10.1097/ACI.0000000000000942","DOIUrl":"10.1097/ACI.0000000000000942","url":null,"abstract":"<p><strong>Purpose of review: </strong>Neurotrophic keratitis is a rare degenerative disease characterized by decrease or absence of corneal sensation. Neurotrophic keratitis varies from mild forms with mild epitheliopathy to severe manifestations such as corneal ulceration, melting and perforation that can lead to irreversible visual loss. The cause of neurotrophic keratitis comprises a long list of diseases, medications, congenital or genetic conditions as well as trauma. The mechanism of neurotrophic keratitis is complex and multifactorial and its understanding is crucial to better address the treatment strategies. We aimed to review neurotrophic keratitis pathology, mechanisms and management.</p><p><strong>Recent findings: </strong>Corneal nerves are critical for the homeostasis of a healthy ocular surface. The lack of nerve-derived neuromediators and corneal-released neuropeptides, neuro-trophins and neurotrophic factors in neurotrophic keratitis leads to a decrease in trophic supply to corneal cells in addition to a decrease in afferent signaling to the brain. This results in pathological tear secretion, decreased blinking rate, corneal healing along with ocular surface and corneal inflammation. Lately, nerve growth factor in special gained emphasis as a treatment strategy targeting the disease mechanism rather than its manifestations. Other therapies, including surgical interventions, are in the pipeline of neurotrophic keratitis management. However, there are still no proper therapeutic guidelines and neurotrophic keratitis treatment remains challenging.</p><p><strong>Summary: </strong>Neurotrophic keratitis may have a devastating outcome and treatment is still challenging. Understanding the disease pathology may assist in the development of new treatment strategies. Prompt disease recognition and immediate intervention are key factors to promote corneal healing and avoid further deterioration.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"520-528"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10194399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monogenic forms of common variable immunodeficiency and implications on target therapeutic approaches.","authors":"Giulio Tessarin, Manuela Baronio, Vassilios Lougaris","doi":"10.1097/ACI.0000000000000947","DOIUrl":"10.1097/ACI.0000000000000947","url":null,"abstract":"<p><strong>Purpose of review: </strong>Common variable immunodeficiency (CVID) is the most common symptomatic inborn error of immunity. The disorder is characterized by variable clinical and immunological manifestations, and, in a small minority of patients, a monogenic cause may be identified. In this review, we focalized on three different monogenic forms of CVID-like disease.</p><p><strong>Recent findings: </strong>Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare disorder characterized by hyperactivated class I phosphatidylinositol-3 kinase (PI3K) pathway. Affected patients present with respiratory infectious episodes, impaired viral clearance and lymphoproliferation. Recently, a direct PI3K inhibitor has been approved and it showed encouraging results both in controlling clinical and immunological manifestations of the disease. On the other hand, patients with defects in CTLA-4 or LRBA gene present with life-threatening immune dysregulation, autoimmunity and lymphocytic infiltration of multiple organs. Abatacept, a soluble cytotoxic T lymphocyte antigen 4 (CTLA-4) fusion protein that acts as a costimulation modulator, has been widely implemented for affected patients with good results as bridge treatment.</p><p><strong>Summary: </strong>Understanding the biological basis of CVID is important not only for enriching our knowledge of the human immune system, but also for setting the basis for potential targeted treatments in this disorder.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"461-466"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ocular surface itch and pain: key differences and similarities between the two sensations.","authors":"Shyamal Raolji, Preet Kumar, Anat Galor","doi":"10.1097/ACI.0000000000000934","DOIUrl":"10.1097/ACI.0000000000000934","url":null,"abstract":"<p><strong>Purpose of review: </strong>To review the pathophysiology and treatment of ocular itch and pain, encompassing nociceptive and neuropathic categories.</p><p><strong>Recent findings: </strong>Ocular itch and pain are sensations that arise from activation of ocular surface polymodal nerves. Nociceptive itch, commonly comorbid with ocular pain complaints, is mainly driven by a histamine-mediated type 1 hypersensitivity reaction. Beyond topical therapy, novel drug delivery systems are being explored to improve ocular residence time of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihistamines. Nociceptive ocular pain can be driven by a variety of factors. Treatment focuses on addressing the causative sources of pain. Neuropathic ocular itch and pain are driven by nerve damage and dysfunction and as such, topical and oral neuromodulation have been explored as treatments. Oral neuromodulators include alpha 2 delta ligands, tricyclic antidepressants (TCAs), and low dose naltrexone. Novel therapies are being evaluated for both modalities such as difelikefalin (κ-opioid receptor agonist) for neuropathic itch and libvatrep (transient receptor potential vanilloid 1 antagonist) for neuropathic pain.</p><p><strong>Summary: </strong>Both ocular itch and pain can be driven by nociceptive and/or neuropathic mechanisms. Identifying contributors to abnormal ocular sensations is vital for precise medical care. Novel therapeutics for these conditions aim to improve patient outcomes and quality of life.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":"23 5","pages":"415-422"},"PeriodicalIF":3.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10133046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial introductions","authors":"","doi":"10.1097/aci.0000000000000938","DOIUrl":"https://doi.org/10.1097/aci.0000000000000938","url":null,"abstract":"Current Opinion in Allergy and Clinical Immunology was launched in 2001. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of allergy and clinical immunology are divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Gianenrico SennaGianenrico SennaDr Gianenrico Senna completed his medical studies at the University School of Medicine in Padua, Italy. In 1985, he became a specialist in internal medicine at the University of Padua and further specialised in allergology and clinical immunology at the University of Pavia, Italy (1988). Presently, he is working as a Medical Consultant in the Allergy Unit and Asthma Center at the University Hospital in Verona, Italy. He is now Elected President of the Italian Society of Allergy Asthma and Clinical Immunology. He is a member of the Anaphylaxis Committee and as well as Scientific Coordinator of the Asthma Committee of the World Allergy Organization (WAO). He cooperates as a referee for: Allergy, Annals of Allergy Asthma Immunology and Respiratory Medicine, and he is a Section Editor for Clinical Molecular Allergy. Dr Senna's research is mainly focused on anaphylaxis and respiratory allergy. He is the author of 225 indexed publications. Mariana CastellsMariana CastellsDr Castells is a clinician, researcher and teacher at Brigham and Women's Hospital and Dana Farber Cancer Institute, USA. She is the Director of the Drug Hypersensitivity and Drug Desensitization Center, as well as the Director of the Mastocytosis Center, and has served as the Allergy and Immunology Training Program Director for 20 years. She served on the Board of Directors of the AAAAI, is on the council of the International College of Allergy (CIA) and has directed the International Drug Desensitization Meeting (DDIM) in Barcelona, Spain, for the last seven years. She has spearheaded the evaluation and understanding of drug anaphylaxis and hypersensitivity and provided desensitization protocols which are used as standards around the world, treating thousands of patients with cancer and chronic inflammatory diseases, maintaining these patients on their first line therapy. Her research has uncovered mast cell inhibitory mechanisms which are pertinent to desensitization. She has been involved in the new diagnostic criteria for mast cell activation disorders and mastocytosis and heads clinical trials created the Mastocytosis Center. Leonard BieloryLeonard BieloryDr Bielory attended Lehigh University in Bethlehem, Pennsylvania, USA, where he completed his BS in Engineering (Fundamental Science) and a Masters in Molecular Biology (1976). He went on to acquire an MD degre","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135170455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atopic dermatitis and ocular allergy: common mechanisms and uncommon questions.","authors":"Debajyoti Ghosh, Tesfaye B Mersha","doi":"10.1097/ACI.0000000000000931","DOIUrl":"10.1097/ACI.0000000000000931","url":null,"abstract":"<p><strong>Purpose of review: </strong>Atopic dermatitis (AD) and ocular allergy aka allergic eye disease (AED) are two common conditions that often coexist in patients. However, molecular connections between these two conditions are incompletely understood. While common etiologic components including Th2 immune signaling have been suggested for AD and AED, the mechanism how current Th2-targetd therapies (dupilumab, tralokinumab) for AD can augment conjunctivitis is not well understood.</p><p><strong>Recent findings: </strong>Differentially regulated genes and pathways relevant for AD disease manifestation are known. In contrast, similar information is not yet available for AED, which could be largely addressed by emerging noninvasive ocular sampling techniques. Emerging evidence indicated a reduction in goblet cell number and mucin production in a subpopulation of AD patients with AD leading to adverse ocular outcomes, while other potential mechanisms could also be involved. Involvement of particular barrier function protein(s) in AED needs further investigation.</p><p><strong>Summary: </strong>Modern cytokine-targeted therapies for AD showed elevated risk for developing conjunctivitis. Recently developed noninvasive sampling techniques should be leveraged to identify AD endotypes associated with AED and with dupilumab-associated ocular outcomes.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":"23 5","pages":"383-389"},"PeriodicalIF":3.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}