{"title":"STAT1 and STAT3 gain of function: clinically heterogenous immune regulatory disorders.","authors":"Peter Olbrich, Alexandra F Freeman","doi":"10.1097/ACI.0000000000001039","DOIUrl":"10.1097/ACI.0000000000001039","url":null,"abstract":"<p><strong>Purpose of review: </strong>The identification of STAT1 gain-of-function (GOF) in 2011 and STAT3 GOF in 2014 has advanced our understanding of the host immunity along the JAK/STAT pathway and allowed targeted treatment approaches. We review the clinical features and pathogenesis of STAT1 and STAT3 GOF and how this has shaped new approaches to therapy.</p><p><strong>Recent findings: </strong>STAT1 GOF, initially described in patients with chronic mucocutaneous candidiasis (CMC) and autoimmune thyroid disease, is now recognized to cause early-onset multisystem autoimmunity and a range of infections. STAT3 GOF comprises mostly lymphoproliferation and autoimmunity but also with varying severity, including some with life threatening organ dysfunction. Treatment has evolved along with the understanding of the pathogenesis, with patients now receiving JAK inhibition to block upstream of the STAT defect with good response in autoimmunity and CMC in STAT1 GOF. Blockade of IL-6 signaling has also been used in STAT3 GOF. Hematopoietic cell transplantation had initial poor outcomes, but outcomes are now improving with focus on the control of inflammation pretransplant.</p><p><strong>Summary: </strong>Understanding the pathogenesis of STAT1 and STAT3 GOF has allowed great recent advancements in therapy, but many questions remain as to the best approach to therapy for each patient's clinical presentation as well as the durability of these therapies.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":"24 6","pages":"440-447"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544286","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.0000000000001038","DOIUrl":"10.1097/ACI.0000000000001038","url":null,"abstract":"","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":"24 6","pages":"v"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544283","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":"Hereditary angioedema due to C1-inhibitor deficiency: current therapeutic approaches.","authors":"Giulia Costanzo, Giada Sambugaro, Davide Firinu","doi":"10.1097/ACI.0000000000001042","DOIUrl":"10.1097/ACI.0000000000001042","url":null,"abstract":"<p><strong>Purpose of review: </strong>For decades, treatment options for hereditary angioedema (HAE) were limited by major adverse effects, insufficient efficacy, and difficult routes of administration. However, the growing body of knowledge regarding HAE pathophysiology has led to the development of innovative drugs for self-administered, on-demand therapy and for short- and long-term prophylaxis. This review provides a comprehensive overview of the approved drugs and the development of HAE treatments.</p><p><strong>Recent findings: </strong>The implementation of new therapies will improve the application of individualized action plans based on the key goals of minimizing the number of attacks and meeting the complex needs of patients.</p><p><strong>Summary: </strong>HAE is a rare genetic disease with a high impact on patients' quality of life due to the unpredictability and variable severity of attacks. Advances in HAE research have allowed optimization of attack management and individualization of therapeutic approaches.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"488-495"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460046","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}
Federica Buta, Giovanni Paoletti, Maria Chiara Bragato, Mattia Giovannini, Giorgio Walter Canonica, Enrico Heffler
{"title":"Real-world evidence of allergen immunotherapy.","authors":"Federica Buta, Giovanni Paoletti, Maria Chiara Bragato, Mattia Giovannini, Giorgio Walter Canonica, Enrico Heffler","doi":"10.1097/ACI.0000000000001026","DOIUrl":"10.1097/ACI.0000000000001026","url":null,"abstract":"<p><strong>Purpose of review: </strong>The full understanding of the long-term effectiveness and safety of allergen immunotherapy (AIT) for allergic respiratory diseases cannot be achieved through randomized controlled trials (RCTs) alone. However, real-world studies designed as registries can complement RCTs.</p><p><strong>Recent findings: </strong>The significance of registries is highlighted by their potential to reassess contraindications and collect data on adult and pediatric patients with multiple comorbidities who are often excluded from RCTs.</p><p><strong>Summary: </strong>AIT is the sole disease-modifying therapeutic approach capable of inducing tolerance and offering a long-term response to allergens. AIT has been shown to play a role in arresting the 'allergic march' in young people, which reduces the risk of developing asthmatic clinical manifestations. Although RCTs are considered the gold standard for evaluating the efficacy and safety of AIT, their duration is usually too short (seldom lasting more than 1 year) to assess the long-term effects of AIT. Several long-term studies show that AIT's effect depends strongly on its use duration.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"529-535"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105220","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}
Inês Pais-Cunha, Cristina Jácome, Rafael Vieira, Bernardo Sousa Pinto, João Almeida Fonseca
{"title":"eHealth in pediatric respiratory allergy.","authors":"Inês Pais-Cunha, Cristina Jácome, Rafael Vieira, Bernardo Sousa Pinto, João Almeida Fonseca","doi":"10.1097/ACI.0000000000001027","DOIUrl":"10.1097/ACI.0000000000001027","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review explores the relevance of eHealth technologies to address unmet needs in pediatric respiratory allergies, particularly allergic rhinitis (AR) and asthma. Given the increasing burden of these conditions, there is a pressing need for effective solutions to enhance disease surveillance, diagnosis, and management.</p><p><strong>Recent findings: </strong>Recent literature highlights the potential of eHealth tools to transform pediatric respiratory allergy care. The use of digital data for infodemiology, application of machine learning models to improve diagnostic sensitivity, smartphone apps with digital patient reported outcome measure (PROMs) and embedded sensors to monitor disease, healthcare professional dashboards with real-time data monitoring and clinical decision support systems (CDSS) are advances emerging to optimize pediatric respiratory allergy care.</p><p><strong>Summary: </strong>Integrating eHealth technologies into the pediatric respiratory allergy care pathway is a potential solution for current healthcare challenges to better meet the needs of children with AR and asthma. However, while the potential of eHealth is evident, its widespread implementation in real-world practice requires continued research, collaboration, and efforts to overcome existing barriers.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"536-542"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281708","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}
Natalia Rodríguez-Otero, Elena Ramírez-Mateo, Maria Nieves Plana, Enrico Heffler, Darío Antolín-Amérigo
{"title":"Cost-effectiveness of allergen immunotherapy.","authors":"Natalia Rodríguez-Otero, Elena Ramírez-Mateo, Maria Nieves Plana, Enrico Heffler, Darío Antolín-Amérigo","doi":"10.1097/ACI.0000000000001028","DOIUrl":"10.1097/ACI.0000000000001028","url":null,"abstract":"<p><strong>Purpose of review: </strong>Allergic rhinitis is a relevant and global health problem affecting up to 5-50% of the general population and its prevalence is increasing due to climate change and pollution among other factors and counts among the 10 most frequent reasons for medical consultation, generating an important economic impact. Allergen immunotherapy (AIT) is the only allergy-disease-modifying treatment and there is plenty of evidence of its effectiveness with regards subcutaneous and oral routes of AIT.This narrative review article examines published literature in the last 24 months regarding the pharmacoeconomics of AIT versus standard of care treatment (SOC) for the treatment of allergic rhinitis and asthma.</p><p><strong>Recent findings: </strong>Farraia et al. assessed in 2022 subcutaneous immunotherapy (SCIT, _438/$500.28) and sublingual immunotherapy (SLIT) (_1021/$1116.19) plus symptomatic treatment versus SOC treatment in children with HDM-driven allergic asthma, measuring QALYs, decrease of medication, decrease of exacerbations and symptoms. They used the cost-effective threshold: _18 482.80 ($21 110.14), finding that AIT is cost-effective.Also, SCIT and SLIT plus symptomatic treatment was assessed versus SOC treatment in children with grass pollen allergic rhinitis. The authors concluded that SCIT (_933/$1065.67) and SLIT (_1408/ $1608.22) seem cost-effective, particularly SCIT.</p><p><strong>Summary: </strong>Allergen immunotherapy is cost-effective in the management of allergic rhinitis and asthma as compared with SOC alone. As most studies consider only during-treatment costs and no long-term benefits or preventive effects are being assessed, the real cost-effectiveness of allergen immunotherapy could be even higher.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"496-503"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371232","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}
Jan Willem N Marsden, Miangela M Laclé, Mirjam Severs, Helen Louisa Leavis
{"title":"Paucity of gastrointestinal plasma cells in common variable immunodeficiency.","authors":"Jan Willem N Marsden, Miangela M Laclé, Mirjam Severs, Helen Louisa Leavis","doi":"10.1097/ACI.0000000000001040","DOIUrl":"10.1097/ACI.0000000000001040","url":null,"abstract":"<p><strong>Purpose of review: </strong>Common variable immunodeficiency enteropathy (CVID-E) is a noninfectious complication of CVID caused by chronic inflammation of the gastrointestinal (GI) tract. Based on literature, a paucity or lack of plasma cells, although not obligatory for diagnosis, is a pathognomonic feature of CVID and more frequent in CVID-E. However, there is no consensus on standardized histopathological analysis of this feature in biopsies. In this systematic review, we highlight methods of reproducible plasma cell quantification of biopsies in CVID and describe the plasma cell counts and classes as presented in the literature.</p><p><strong>Recent findings: </strong>Reduced plasma cell counts are commonly found over the entire GI tract, except for in the oesophagus. Immunoglobulin A+ (IgA+) plasma cells appear to be the most commonly reduced plasma cell class in CVID, yet there is scarce literature on the predictive value of low IgA+ plasma cell counts in CVID-E.</p><p><strong>Summary: </strong>We propose two optimized methodologies of quantification using a cut-of value of <10 plasma cells per HPF at 40× magnification, or a proportion of ≥1-5% of total mononuclear cells, recorded over ≥3 sections, and in ≥2 biopsies, as the most conservative agreeable definitions for a paucity of plasma cells to be used in diagnostics and further research.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":"24 6","pages":"464-471"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544285","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}
Helena Buso, Clément Triaille, Aisling M Flinn, Andrew R Gennery
{"title":"Update on hereditary C1q deficiency: pathophysiology, clinical presentation, genotype and management.","authors":"Helena Buso, Clément Triaille, Aisling M Flinn, Andrew R Gennery","doi":"10.1097/ACI.0000000000001034","DOIUrl":"10.1097/ACI.0000000000001034","url":null,"abstract":"<p><strong>Purpose of review: </strong>C1q deficiency is a rare inborn error of immunity characterized by susceptibility to severe infections and profound immune dysregulation, with a systemic lupus erythematosus-like phenotype. The management of patients with C1q deficiency is challenged by the rarity of this condition and the wide clinical variability. This review aims to emphasize the importance of a thorough immunological and clinical characterization to help guide a personalized and comprehensive approach to patients.</p><p><strong>Recent findings: </strong>We focus on the concept of C1q deficiency as a bridge between the monogenic form of systemic lupus erythematosus and the Mendelian type I interferonopathies. Moreover, we explore the role of new treatment strategies such as Janus-associated kinase (JAK) inhibitors and allogeneic stem cell transplantation.</p><p><strong>Summary: </strong>In this narrative review, we provide a systematic overview of C1q deficiency, starting with the description of the pathophysiological background and the variable clinical phenotype, and then exploring the different prognoses, the consequent treatment strategies and future directions.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":"24 6","pages":"427-433"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544287","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":"Allergen-specific immunotherapy at the extremes of age: below 5 years and elderly: evidence beyond indications?","authors":"Cansu Özdemiral, Deniz Ilgun Gurel, Umit Sahiner","doi":"10.1097/ACI.0000000000001030","DOIUrl":"10.1097/ACI.0000000000001030","url":null,"abstract":"<p><strong>Purpose of review: </strong>Allergen-specific immunotherapy (AIT) has been used in clinical practice to treat allergic diseases for over 100 years. The effectiveness and safety of AIT have been substantiated in numerous studies; however, children before 5 years of age and elderly are not encompassed generally. This review aims to present the current understanding of AIT in the extremes of age.</p><p><strong>Recent findings: </strong>Early allergen immunotherapy during infancy or early childhood may prevent the development of allergic sensitization to common allergens, thereby reducing the risk of developing allergic diseases later in life. In the elderly, improved symptoms and quality of life and reduced dependence on medication are indicated the importance on the implementation of AIT. Both clinical and immunological parameters demonstrated that the treatment was effective at the time of cessation and trend to sustained tolerance.</p><p><strong>Summary: </strong>There is no specific lower or upper age limit for initiating immunotherapy; however, it is important to thoroughly evaluate the severity of disease and the risks and benefits in each case.</p>","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":" ","pages":"510-519"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343324","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":"Editorial introductions.","authors":"","doi":"10.1097/ACI.0000000000001038","DOIUrl":"https://doi.org/10.1097/ACI.0000000000001038","url":null,"abstract":"","PeriodicalId":10956,"journal":{"name":"Current Opinion in Allergy and Clinical Immunology","volume":"24 6","pages":"v"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946141","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}