Jan Hendrik Niess, Ashley Kimberley Heinsalo, Hassan Melhem
{"title":"Potential approaches in repairing the damaged epithelial barrier in eosinophilic esophagitis.","authors":"Jan Hendrik Niess, Ashley Kimberley Heinsalo, Hassan Melhem","doi":"10.1080/1744666X.2026.2641531","DOIUrl":"10.1080/1744666X.2026.2641531","url":null,"abstract":"<p><strong>Introduction: </strong>Eosinophilic esophagitis, or short EoE, is a chronic, food- and aeroallergen-driven type 2 inflammation strongly linked to epithelial barrier dysfunction, causing dysphagia and food impaction. We discuss the key question of whether barrier damage initiates the disease by allowing allergen penetration across the epithelium, or whether epithelial disruption results secondarily from inflammation.</p><p><strong>Areas covered: </strong>This review examines current evidence of structural and functional epithelial defects in EoE, including abnormalities in junctional proteins, impaired cell differentiation, and increased permeability, based on a literature search in PubMed and Google Scholar. These defects stem from environmental or dietary exposures in individuals with genetic susceptibility, as evidenced by genome-wide association studies that identify genes crucial for epithelial structure and regulation. It also assesses the extent to which barrier dysfunction is caused by inflammatory cytokines, especially IL-13 and other type 2 cytokines, which directly alter epithelial architecture. Lastly, we explore emerging strategies to strengthen or repair the epithelial barrier, ranging from dietary interventions and biologics to approaches targeting epithelial metabolism, protease balance, and hormonal pathways.</p><p><strong>Expert opinion: </strong>Maintaining epithelial integrity is essential for preventing and treating EoE. Future treatments should directly reinforce the epithelial barrier, unlike current treatment options that reduce type 2 inflammation.</p>","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"145-154"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel indications for hematopoietic stem cell transplantation in inborn errors of immunity.","authors":"Alexandra Laberko, Andrew R Gennery","doi":"10.1080/1744666X.2026.2641540","DOIUrl":"10.1080/1744666X.2026.2641540","url":null,"abstract":"<p><strong>Introduction: </strong>Hematopoietic stem cell transplantation (HSCT) is a curative treatment for an expanding spectrum of inborn errors of immunity (IEI). Whilst the utility and success of this treatment is well established for common, or historically described IEI (severe combined immunodeficiency, Wiskott-Aldrich syndrome, CD40L deficiency, the role of HSCT for emerging, newly described IEI is less clear. This review examines HSCT results for recently described IEI or those in which HSCT has only recently and rarely been employed.</p><p><strong>Areas covered: </strong>The literature search included HSCT in IEI from 2020 to 2025. We report the HSCT experience and outcome in newly described diseases including RIPK1, ARPC1B, CD27/CD70 deficiency. More established diseases for which HSCT has only recently been reported are described, including female carriers of X-linked chronic granulomatous disease, and X-linked agammaglobulinemia. We report on recently described diseases with limited HSCT experience including CTLA-4/LRBA deficiency, STAT1 gain-of-function. Finally, we consider diseases where HSCT has previously been considered inappropriate, like STAT3 loss-of-function.</p><p><strong>Expert opinion: </strong>Previous experience implies that younger age and fewer co-morbidities at time of HSCT improve outcomes, but limited natural history data combined with increased use of targeted therapies make HSCT decisions difficult in new diseases. Adoption of disease-appropriate scoring tools may aid decision making.</p>","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"183-193"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Veronica Batani, Jelena Colic, Cristina Scaletti, Raffaella Molteni, Giacomo De Luca, Giulia Bandini, Lorenzo Dagna, Francesco Annunziato, Marco Matucci-Cerinic, Corrado Campochiaro
{"title":"Drug development in systemic sclerosis: novel therapeutics to watch.","authors":"Veronica Batani, Jelena Colic, Cristina Scaletti, Raffaella Molteni, Giacomo De Luca, Giulia Bandini, Lorenzo Dagna, Francesco Annunziato, Marco Matucci-Cerinic, Corrado Campochiaro","doi":"10.1080/1744666X.2026.2636654","DOIUrl":"10.1080/1744666X.2026.2636654","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic sclerosis (SSc) is increasingly understood as a triad of immune dysregulation, progressive fibrosis, and vasculopathy that evolve in parallel. The literature search was conducted using PubMed/MEDLINE, ClinicalTrials.gov, and the European Clinical Trials Database (EudraCT), including studies published in English up to October 2025.</p><p><strong>Areas covered: </strong>This review summarizes the most recent therapeutic strategies now in clinical development and links each to its underpinning pre‑clinical and translational evidence, thereby mapping how mechanistic insights are reshaping drug pipeline in SSc.</p><p><strong>Expert opinion: </strong>A key breakthrough is the emergence of cell‑based immunotherapies, bispecific antibodies, and next‑generation small molecules that extend beyond adaptive immune targets to modulate innate immunity directly. Collectively, these agents illustrate a unifying concept: successful disease modification will require the synchronous interception of inflammation, fibrotic remodeling, and vascular injury rather than approaching these domains independently.</p>","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"155-173"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The relationship between MMP-2 and TIMP-2 gene polymorphisms and skin barrier function, inflammatory cytokine levels in acne patients.","authors":"Suling Huang, Lijia Fang, Meina Zhang, Shuxian Sun, Huixian Zhi, Yuguang Zhu, Hong Zhang","doi":"10.1080/1744666X.2026.2636646","DOIUrl":"10.1080/1744666X.2026.2636646","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the association between MMP-2 rs243865 and TIMP-2 rs8179090 gene polymorphisms and skin barrier function, as well as inflammatory cytokine levels, in acne patients, to explore potential genetic mechanisms underlying acne pathogenesis.</p><p><strong>Methods: </strong>A total of 200 acne patients and 100 healthy controls were enrolled. Genotyping was performed using PCR-RFLP. Skin barrier function was assessed via transepidermal water loss (TEWL) and hydration measurements. Serum levels of IL-1β and TNF-α were quantified by ELISA. Statistical analyses included Pearson correlation and logistic regression.</p><p><strong>Results: </strong>The MMP-2-CC and TIMP-2-CC genotypes were significantly more prevalent in acne patients (<i>p</i> < 0.05). These genotypes correlated with higher TEWL (<i>p</i> < 0.05), reduced skin hydration (<i>p</i> < 0.05), and elevated IL-1β and TNF-α levels (<i>p</i> < 0.05) compared to CT/TT genotypes. Logistic regression confirmed associations between CC genotypes and increased acne severity (OR = 1.86-2.24).</p><p><strong>Conclusion: </strong>The MMP-2 and TIMP-2 CC genotypes are linked to impaired skin barrier function and heightened inflammation in acne, suggesting their role in genetic susceptibility and disease progression. These findings may inform future targeted therapies.</p><p><strong>Clinical trial registration: </strong>www.clinicaltrials.gov identifier is NCT07069075.</p>","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"233-241"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joshua A Lawson, Ulfat A Khanam, Donna Goodridge, Mark A Ferro, Darryl Adamko, Lloyd Balbuena, Don W Cockcroft, Michelle Pavloff, Brianne Philipenko, Jenna Pylypow, Grzegorz Brozek
{"title":"Asthma and neurodevelopmental and mental health disorder (NMD) multimorbidity in rural children.","authors":"Joshua A Lawson, Ulfat A Khanam, Donna Goodridge, Mark A Ferro, Darryl Adamko, Lloyd Balbuena, Don W Cockcroft, Michelle Pavloff, Brianne Philipenko, Jenna Pylypow, Grzegorz Brozek","doi":"10.1080/1744666X.2026.2634846","DOIUrl":"10.1080/1744666X.2026.2634846","url":null,"abstract":"<p><strong>Introduction: </strong>Asthma coupled with neurodevelopmental and mental disorders (NMD) is an important childhood issue. Children living in rural areas may experience unique exposures or require novel health care approaches. The purpose of this report is to explore the effects of rural dwelling on the relationship between childhood asthma and NMDs.</p><p><strong>Areas covered: </strong>Medline, Embase, CINAHL, and APA databases were searched from date of inception up to February 2025. Few studies investigated the role of rural dwelling on the relationship between childhood asthma and NMDs. Of those, purpose, methods and sampling varied greatly. Despite this, there is evidence of differences in the frequency of childhood asthma-NMD multimorbidity (CANM) between urban and rural areas, albeit with some inconsistency, as well as some indication of rural specific interventions improving health outcomes. A major gap is the lack of evidence about the role of rural dwelling on the impact of CANM.</p><p><strong>Expert opinion: </strong>Consideration of rurality on CANM should be a focal point of research and practice; this may contribute to the understanding of CANM etiology. In addition, needs of rural dwellers should drive the development of novel forms of health care delivery. These approaches will address research and care gaps around CANM.</p>","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"211-221"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Past, present and future of lupus nephritis.","authors":"Claudio Ponticelli, Gabriella Moroni","doi":"10.1080/1744666X.2026.2637769","DOIUrl":"10.1080/1744666X.2026.2637769","url":null,"abstract":"<p><strong>Introduction: </strong>Our objective is to delineate the evolution of lupus nephritis (LN) histological classifications and management, from their origins to the present histopathological framework and treatment strategies, and to consider prospective future directions.</p><p><strong>Areas covered: </strong>We describe the origins and progressive development of LN, particularly on histological classifications and pharmacological approaches to prevent renal disease progression and disease flares between 1950 and 2000 (the Past). Then, we discuss the remarkable advances achieved from 2001 to the present in the management, prognosis, and understanding of LN(the Present). Then, we envision a future shaped by the broader adoption of personalized medicine, the integration of novel biomarkers and artificial intelligence, and the innovative therapeutic strategies (the Future). Bibliography was searched in databases including PubMed, Medline, and Embase.</p><p><strong>Expert opinion: </strong>Despite improvement in LN diagnosis and management, many patients experience a poor quality of life and may progress to renal failure or die from complications often associated with immunosuppressive therapy. Future strategies are expected to make substantial contributions to the field of LN, including the identification of novel biomarkers, the application of artificial intelligence, the implementation of personalized medicine, and the development of innovative therapies improving long-term renal survival and patients' quality of life.</p>","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"195-209"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147304337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Skin toxicities related to Bruton tyrosine kinase inhibitors: an updated review.","authors":"Stephano Cedirian, Vito Epifani, Gianluca Cafasso, Tullio Brunetti, Michela Starace, Alba Guglielmo, Corrado Zengarini, Beatrice Casadei, Gianmarco Bagnato, Pierluigi Zinzani, Alessandro Pileri","doi":"10.1080/1744666X.2026.2634839","DOIUrl":"10.1080/1744666X.2026.2634839","url":null,"abstract":"<p><strong>Introduction: </strong>Bruton's tyrosine kinase inhibitors (BTKi) have transformed the management of B-cell malignancies by selectively targeting signaling pathways essential for malignant B-cell survival, thereby reducing the systemic toxicity of conventional chemotherapy. However, with their expanding use, cutaneous adverse events are increasingly recognized as clinically relevant complications that may affect quality of life and treatment adherence.</p><p><strong>Areas covered: </strong>This review provides an updated overview of first- and second-generation BTKi, including ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib, with a specific focus on dermatologic toxicities. A comprehensive literature search was conducted using PubMed, Embase, and Scopus, covering publications up to February 2025. Clinical studies, case series, and case reports describing skin-related adverse events associated with BTKi therapy were reviewed.</p><p><strong>Expert opinion: </strong>Cutaneous toxicities related to BTKi are often underrecognized but clinically significant, ranging from xerosis and bruising to lichenoid eruptions and vasculitis. First-generation agents, particularly ibrutinib, are associated with a broader spectrum of dermatologic adverse events, whereas newer BTKi show improved selectivity and potentially reduced skin toxicity. Early recognition, standardized dermatologic evaluation, and proactive multidisciplinary management are essential to minimize patient discomfort, preserve quality of life, and prevent unnecessary treatment discontinuation.</p>","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"175-182"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ilenia Di Cola, Chiara Castellini, Marta Vomero, Roberto Giacomelli, Piero Ruscitti
{"title":"The role of interleukin-15 in the spectrum of inflammatory diseases.","authors":"Ilenia Di Cola, Chiara Castellini, Marta Vomero, Roberto Giacomelli, Piero Ruscitti","doi":"10.1080/1744666X.2025.2611897","DOIUrl":"10.1080/1744666X.2025.2611897","url":null,"abstract":"<p><strong>Introduction: </strong>Interleukin-15 (IL-15) is a pleiotropic, pro-inflammatory cytokine, constitutively expressed in both hematopoietic and non-hematopoietic cells. The role of IL-15 during systemic inflammatory diseases, including autoimmune and autoinflammatory disorders, is to be fully clarified yet. Due to its effects on immune cells, IL-15 has attracted attention as a potential new therapeutic target for modulating immune responses, either by enhancing immune surveillance or by controlling excessive inflammation.</p><p><strong>Areas covered: </strong>We provided a landscape about IL-15 in systemic inflammatory diseases, from its biological functions to the possible mechanistic roles, using rheumatoid arthritis (RA) and Still's disease as autoimmune and autoinflammatory models, respectively.</p><p><strong>Expert opinion: </strong>IL-15 exerts its pathogenetic activity by the induction of a deregulated activation of innate and adaptive arms of the immune system, at the crossroad of autoimmune and autoinflammatory disorders. During RA, IL-15 mediates the production from T cells and macrophages of TNF, which may induce further production of IL-15 by synoviocytes via a vicious pathogenic loop. During Still's disease, together with IFN-I, IL-15 promotes the expansion of NK cells and of CD38+HLA-DR+ T cells, which are highly activated in disease life-threatening evolution. Thus, novel IL-15-targeted therapeutic strategies could be explored to improve the management of systemic inflammatory diseases.</p>","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"1-10"},"PeriodicalIF":3.7,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CAR-T cell immunotherapy of malignant melanoma.","authors":"Olha Kharasakhal, John Maher","doi":"10.1080/1744666X.2026.2621811","DOIUrl":"10.1080/1744666X.2026.2621811","url":null,"abstract":"<p><strong>Introduction: </strong>Management of inoperable and advanced malignant melanoma has been transformed in recent years by the advent of a number of approaches, including immune checkpoint blockade, small-molecule inhibitors, and adoptive immunotherapy with ex vivo expanded tumor-infiltrating lymphocytes.</p><p><strong>Areas covered: </strong>In this review, we describe efforts made to develop an alternative immunotherapeutic approach for this disease using chimeric antigen receptor (CAR) engineered T-cells. Literature was reviewed in the PubMed database and clinicaltrials.gov website (1998-2025).</p><p><strong>Expert opinion: </strong>CAR T-cell immunotherapy has proven transformative in the treatment of selected hematological malignancies. However, solid tumors such as melanoma remain much more challenging to treat using this emerging modality. Here we consider issues surrounding target selection, encompassing both tumor cells and accompanying stroma, in addition to armoring approaches that may potentiate delivery to or efficacy within the tumor microenvironment. We also consider a number of advanced CAR-based architectures to enable multi-antigen or universal antigen targeting and combination-based approaches.</p>","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"43-59"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ghaith Noaiseh, Kathy L Sivils, Kim Campbell, Jada Idokogi, Kim Hung Lo, Sophia G Liva, Jocelyn H Leu, Harman Dhatt, Keying Ma, Steven Leonardo, He Li, Jonathan J Hubbard, Jacques-Eric Gottenberg
{"title":"Nipocalimab for the treatment of moderate-to-severe Sjögren's disease: a plain language summary of the DAHLIAS study.","authors":"Ghaith Noaiseh, Kathy L Sivils, Kim Campbell, Jada Idokogi, Kim Hung Lo, Sophia G Liva, Jocelyn H Leu, Harman Dhatt, Keying Ma, Steven Leonardo, He Li, Jonathan J Hubbard, Jacques-Eric Gottenberg","doi":"10.1080/1744666X.2026.2623948","DOIUrl":"10.1080/1744666X.2026.2623948","url":null,"abstract":"","PeriodicalId":12175,"journal":{"name":"Expert Review of Clinical Immunology","volume":" ","pages":"5-18"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}