Frontiers in allergyPub Date : 2024-10-10eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1473352
Maurizio Mennini, Marisa Piccirillo, Silvia Furio, Francesco Valitutti, Alessandro Ferretti, Caterina Strisciuglio, Maria De Filippo, Pasquale Parisi, Diego Giampietro Peroni, Giovanni Di Nardo, Federica Ferrari
{"title":"Probiotics and other adjuvants in allergen-specific immunotherapy for food allergy: a comprehensive review.","authors":"Maurizio Mennini, Marisa Piccirillo, Silvia Furio, Francesco Valitutti, Alessandro Ferretti, Caterina Strisciuglio, Maria De Filippo, Pasquale Parisi, Diego Giampietro Peroni, Giovanni Di Nardo, Federica Ferrari","doi":"10.3389/falgy.2024.1473352","DOIUrl":"https://doi.org/10.3389/falgy.2024.1473352","url":null,"abstract":"<p><p>This review delves into the potential of manipulating the microbiome to enhance oral tolerance in food allergy, focusing on food allergen-specific immunotherapy (FA-AIT) and the use of adjuvants, with a significant emphasis on probiotics. FA-AIT, including oral (OIT), sublingual (SLIT), and epicutaneous (EPIT) immunotherapy, has shown efficacy in desensitizing patients and achieving sustained unresponsiveness (SU). However, the long-term effectiveness and safety of FA-AIT are still under investigation. Probiotics, particularly strains of Lactobacillus, play a crucial role in enhancing immune tolerance by promoting regulatory T cells (Tregs) and modulating cytokine profiles. These probiotics can induce semi-mature dendritic cells, enhance CD40 expression, inhibit IL-4 and IL-5, and promote IL-10 and TGF-β, thus contributing to mucosal defense and immunological tolerance. Clinical trials combining probiotics with FA-AIT have demonstrated improved desensitization rates and immune tolerance in food-allergic patients. For example, the combination of Lactobacillus rhamnosus with peanut OIT resulted in a significantly higher rate of SU compared to the placebo group, along with notable immune changes such as reduced peanut-specific IgE and increased IgG4 levels. The review also explores other adjuvants in FA-AIT, such as biologic drugs, which target specific immune pathways to improve treatment outcomes. Additionally, nanoparticles and herbal therapies like food allergy herbal formula 2 (FAHF-2) are discussed for their potential to enhance allergen delivery and immunogenicity, reduce adverse events, and improve desensitization. In conclusion, integrating probiotics and other adjuvants into FA-AIT protocols could significantly enhance the safety and efficacy of FA-AIT, leading to better patient outcomes and quality of life.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in allergyPub Date : 2024-10-07eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1458688
Juliane Wurm, Nigel Curtis, Petra Zimmermann
{"title":"The effect of antibiotics on the intestinal microbiota in children - a systematic review.","authors":"Juliane Wurm, Nigel Curtis, Petra Zimmermann","doi":"10.3389/falgy.2024.1458688","DOIUrl":"10.3389/falgy.2024.1458688","url":null,"abstract":"<p><strong>Background: </strong>Children are the age group with the highest exposure to antibiotics (ABX). ABX treatment changes the composition of the intestinal microbiota. The first few years of life are crucial for the establishment of a healthy microbiota and consequently, disturbance of the microbiota during this critical period may have far-reaching consequences. In this review, we summarise studies that have investigated the effect of ABX on the composition of the intestinal microbiota in children.</p><p><strong>Methods: </strong>According to the PRISMA guidelines, a systematic search was done using MEDLINE and Embase to identify original studies that have investigated the effect of systemic ABX on the composition of the intestinal microbiota in children.</p><p><strong>Results: </strong>We identified 89 studies investigating a total of 9,712 children (including 4,574 controls) and 14,845 samples. All ABX investigated resulted in a reduction in alpha diversity, either when comparing samples before and after ABX or children with ABX and controls. Following treatment with penicillins, the decrease in alpha diversity persisted for up to 6-12 months and with macrolides, up to the latest follow-up at 12-24 months. After ABX in the neonatal period, a decrease in alpha diversity was still found at 36 months. Treatment with penicillins, penicillins plus gentamicin, cephalosporins, carbapenems, macrolides, and aminoglycosides, but not trimethoprim/sulfamethoxazole, was associated with decreased abundances of beneficial bacteria including Actinobacteria, <i>Bifidobacteriales</i>, <i>Bifidobacteriaceae,</i> and/or <i>Bifidobacterium</i>, and <i>Lactobacillus.</i> The direction of change in the abundance of <i>Enterobacteriaceae</i> varied with ABX classes, but an increase in <i>Enterobacteriaceae</i> other than <i>Escherichia coli</i> was frequently observed.</p><p><strong>Conclusion: </strong>ABX have profound effects on the intestinal microbiota of children, with notable differences between ABX classes. Macrolides have the most substantial impact while trimethoprim/sulfamethoxazole has the least pronounced effect.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in allergyPub Date : 2024-10-02eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1464466
V Schichter-Konfino, R Mubariki, E Toubi, Z Vadasz
{"title":"The prevalence of patients suffering from chronic spontaneous urticaria, in whom omalizumab cannot be stopped even after six years.","authors":"V Schichter-Konfino, R Mubariki, E Toubi, Z Vadasz","doi":"10.3389/falgy.2024.1464466","DOIUrl":"https://doi.org/10.3389/falgy.2024.1464466","url":null,"abstract":"<p><strong>Background: </strong>Omalizumab (OMA) was the first FDA-approved biological drug for severe chronic spontaneous urticaria (CSU), and until today is the only beneficial and truly safe one. The objectives were: To assess the prevalence of CSU patients in whom OMA cannot be stopped over time. We also asked if biomarkers (e.g., anti-TPO antibodies and total IgE) could assist in anticipating this issue.</p><p><strong>Methods: </strong>We used our prospective registry of 93 patients, which included CSU disease duration, the onset of OMA treatment, Urticaria Activity Score (UAS7) during follow-up, co-morbidities, serum IgE levels and the presence of anti-TPO antibodies. Finally, we assessed the response to OMA during a period of six years.</p><p><strong>Results: </strong>Out of the 93 treated CSU patients, OMA was stopped in ten patients after six months being defined as failures. In another ten patients, OMA was discontinued after 2-4 years of therapy, achieving a remission. Seventy-three patients are still treated between 2 and 6 years, having different degrees of response. Of these, in thirty-eight (52%) patients, we could not stop OMA even after six years due to CSU relapses. The prevalence of lower serum IgE levels and anti-TPO antibody positivity was significantly higher in CSU patients in whom OMA could not be stopped.</p><p><strong>Conclusion: </strong>This is the first study where OMA-treated CSU patients were followed up to six years. In half of them, long-term therapy of six years is still required.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in allergyPub Date : 2024-09-30eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1467245
Anneli Graner, Ralf S Mueller, Johanna Geisler, Delia Bogenstätter, Samuel J White, Sigridur Jonsdottir, Eliane Marti
{"title":"Allergen immunotherapy using recombinant <i>Culicoides</i> allergens improves clinical signs of equine insect bite hypersensitivity.","authors":"Anneli Graner, Ralf S Mueller, Johanna Geisler, Delia Bogenstätter, Samuel J White, Sigridur Jonsdottir, Eliane Marti","doi":"10.3389/falgy.2024.1467245","DOIUrl":"https://doi.org/10.3389/falgy.2024.1467245","url":null,"abstract":"<p><strong>Introduction: </strong>Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis of horses caused by bites of <i>Culicoides</i> spp., sharing some common features with human atopic dermatitis. Allergen immunotherapy (AIT) using <i>Culicoides</i> whole-body extracts has limited efficacy. This study aimed to evaluate AIT with a pool of major <i>Culicoides</i> recombinant allergens in a prospective, double-blinded, placebo-controlled study.</p><p><strong>Methods: </strong>The IBH lesion score was assessed during a pre-treatment year and first treatment year (May-October) in 17 horses and in May and July of a second treatment year. Nine horses were immunized subcutaneously 3× with a combination of nine r-allergens (20 μg each/injection) in alum and monophosphoryl lipid A (MPLA). Eight horses received a placebo. The immunization was repeated twice the following year. The specific antibody response to one of the AIT <i>Culicoides</i> r-allergens was assessed.</p><p><strong>Results: </strong>In the first treatment year, the decrease in average IBH lesion score was significantly larger in the AIT compared to the placebo group, with 67% of the AIT group and 25% of the placebo horses reaching >50% improvement of the average IBH lesion score. The response to the AIT was enhanced in the 2nd treatment year when 89% of the AIT vs. 14% of the placebo horses showed an improvement (<i>p</i> ≤ 0.01). IgG antibodies of all subclasses were induced, with IgG4/7 showing the most significant differences between groups. The post-AIT sera showed IgE blocking activity.</p><p><strong>Discussion: </strong>AIT using only a few injections of small amounts of r-allergens in alum and MPLA as immunomodulators seems a promising approach for the treatment of insect bite allergy.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in allergyPub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1438252
Margherita Farnetano, Laura Carucci, Serena Coppola, Franca Oglio, Antonio Masino, Marica Cozzolino, Rita Nocerino, Roberto Berni Canani
{"title":"Gut microbiome features in pediatric food allergy: a scoping review.","authors":"Margherita Farnetano, Laura Carucci, Serena Coppola, Franca Oglio, Antonio Masino, Marica Cozzolino, Rita Nocerino, Roberto Berni Canani","doi":"10.3389/falgy.2024.1438252","DOIUrl":"10.3389/falgy.2024.1438252","url":null,"abstract":"<p><p>Increasing evidence suggests that alterations in the gut microbiome (GM) play a pivotal role in the pathogenesis of pediatric food allergy (FA). This scoping review analyzes the current evidence on GM features associated with pediatric FAs and highlights the importance of the GM as a potential target of intervention for preventing and treating this common condition in the pediatric age. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we searched PubMed and Embase using the keywords (gut microbiome OR dysbiosis OR gut microbiota OR microbiome signatures) AND (food allergy OR IgE-mediated food allergy OR food protein-induced allergic proctocolitis OR food protein-induced enterocolitis OR non-IgE food allergy OR cow milk allergy OR hen egg allergy OR peanut allergy OR fish allergy OR shellfish allergy OR tree nut allergy OR soy allergy OR wheat allergy OR rice allergy OR food sensitization). We included 34 studies reporting alterations in the GM in children affected by FA compared with healthy controls. The GM in pediatric FAs is characterized by a higher abundance of harmful microorganisms (e.g., Enterobacteriaceae, <i>Clostridium sensu stricto</i>, <i>Ruminococcus gnavus</i>, and <i>Blautia</i> spp.) and lower abundance of beneficial bacteria (e.g., Bifidobacteriaceae, <i>Lactobacillaceae</i>, some <i>Bacteroides</i> species). Moreover, we provide an overview of the mechanisms of action elicited by these bacterial species in regulating immune tolerance and of the main environmental factors that can modulate the composition and function of the GM in early life. Altogether, these data improve our knowledge of the pathogenesis of FA and can open the way to innovative diagnostic, preventive, and therapeutic strategies for managing these conditions.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in allergyPub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1437600
Wesam A Boghdady, Marwa A Khairy, Ali G Ali, Alia A El Shahawy, Eman A Abdelaziz, Aya A El Shahawy, Fatma Z Kamel
{"title":"Correlation between forkhead box P3 (rs3761548) gene polymorphism and serum interleukin13 as biomarkers of severity in Egyptian allergic conjunctivitis: a retrospective study.","authors":"Wesam A Boghdady, Marwa A Khairy, Ali G Ali, Alia A El Shahawy, Eman A Abdelaziz, Aya A El Shahawy, Fatma Z Kamel","doi":"10.3389/falgy.2024.1437600","DOIUrl":"10.3389/falgy.2024.1437600","url":null,"abstract":"<p><strong>Introduction: </strong>The genetic variants that alter human Forkhead Box P3 (<i>FOXP3</i>) function may have a part in the establishment of allergic conjunctivitis. Our study aimed to evaluate the <i>FOXP3</i> polymorphism, serum interleukin13 (IL13) and total immunoglobulin E (IgE) levels in allergic conjunctivitis and assess their role as biomarkers for allergic conjunctivitis risk and severity.</p><p><strong>Methods: </strong>This study included 52 cases and 52 controls. Blood samples were taken from allergic conjunctivitis patients and controls for total IgE, IL13 measurement and detection of <i>FOXP3</i> (rs3761548) gene polymorphism.</p><p><strong>Results: </strong>There was a statistically significant difference between the allergic conjunctivitis group and healthy control group regarding <i>FOXP3</i> (rs3761548) polymorphism with those have AA genotype are 12 times at risk for allergic conjunctivitis and A allele increases the risk of allergic conjunctivitis by about 4 times. There was statistically significant difference between mild/moderate and severe allergic conjunctivitis regarding <i>FOXP3</i> (rs3761548) polymorphism with those have AA genotype are 53 times at risk for severe allergic conjunctivitis and A allele increases the risk of severe allergic conjunctivitis by about 6 times. Also, there was a significantly higher value of total IgE IU/ml, IL13 Pg/ml value in severe allergic conjunctivitis compared to moderate/mild allergic conjunctivitis. The best cutoff values of total IgE and serum IL13 for detecting the severity of allergic conjunctivitis were ≥320 IU/ml and ≥40 Pg/ml and the area under the curve were 0.89 and 0.95 respectively.</p><p><strong>Conclusion: </strong>The research significantly contributes to find correlation of <i>FOXP3</i> polymorphism, total IgE and IL13 with risk and severity of allergic conjunctivitis which are limited in the literature on the perceived value relevance of <i>FOXP3</i> polymorphism in allergic conjunctivitis risk and severity.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in allergyPub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1484624
Julie Weidner, Haisheng Hu, Xiangqing Hou, Baoqing Sun
{"title":"Editorial: The application of new technology in the diagnosis of allergic diseases.","authors":"Julie Weidner, Haisheng Hu, Xiangqing Hou, Baoqing Sun","doi":"10.3389/falgy.2024.1484624","DOIUrl":"10.3389/falgy.2024.1484624","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in allergyPub Date : 2024-09-24eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1387774
Enze Wang, Yingxuan Sun, He Zhao, Meng Wang, Zhiwei Cao
{"title":"Genetic correlation between chronic sinusitis and autoimmune diseases.","authors":"Enze Wang, Yingxuan Sun, He Zhao, Meng Wang, Zhiwei Cao","doi":"10.3389/falgy.2024.1387774","DOIUrl":"https://doi.org/10.3389/falgy.2024.1387774","url":null,"abstract":"<p><strong>Objective: </strong>The association between autoimmune diseases and chronic rhinosinusitis in observational studies remains unclear. This study aimed to explore the genetic correlation between chronic rhinosinusitis and autoimmune diseases.</p><p><strong>Methods: </strong>We employed Mendelian randomization (MR) analysis and linkage disequilibrium score regression (LDSC) to investigate causal relationships and genetic correlations between autoimmune phenotypes and chronic rhinosinusitis. Additionally, transcriptome-wide association (TWAS) analysis was conducted to identify the shared genes between the two conditions to demonstrate their relationship. The CRS GWAS (genome-wide association study) data and other autoimmune diseases were retrieved from ieuOpenGWAS (https://gwas.mrcieu.ac.uk/), the FinnGen alliance (https://r8.finngen.fi/), the UK Biobank (https://www.ukbiobank.ac.uk/), and the EBI database (https://www.ebi.ac.uk/).</p><p><strong>Results: </strong>Utilizing a bivariate two-sample Mendelian randomization approach, our findings suggest a significant association of chronic rhinosinusitis with various autoimmune diseases, including allergic rhinitis (<i>p</i> = 9.55E-10, Odds Ratio [OR] = 2,711.019, 95% confidence interval [CI] = 261.83391-28,069.8), asthma (<i>p</i> = 1.81E-23, OR = 33.99643, 95%CI = 17.52439-65.95137), rheumatoid arthritis (<i>p</i> = 9.55E-10, OR = 1.115526, 95%CI = 1.0799484-1.1522758), hypothyroidism (<i>p</i> = 2.08828E-2, OR = 4.849254, 95%CI = 1.7154455-13.707962), and type 1 diabetes (<i>p</i> = 2.08828E-2, OR = 01.04849, 95%CI = 1.0162932-1.0817062). LDSC analysis revealed a genetic correlation between the positive autoimmune phenotypes mentioned above and chronic rhinosinusitis: AR (rg = 0.344724754, <i>p</i> = 3.94E-8), asthma (rg = 0.43703672, <i>p</i> = 1.86E-10), rheumatoid arthritis (rg = 0.27834931, <i>p</i> = 3.5376E-2), and hypothyroidism (rg = -0.213201473, <i>p</i> = 3.83093E-4). Utilizing the Transcriptome-Wide Association Studies (TWAS) approach, we identified several genes commonly associated with both chronic rhinosinusitis and autoimmune diseases. Genes such as TSLP/WDR36 (Chromosome 5, top SNP: rs1837253), ORMDL3 (Chromosome 13, top SNP: rs11557467), and IL1RL1/IL18R1 (Chromosome 2, top SNP: rs12905) exhibited a higher degree of consistency in their shared involvement across atopic dermatitis (AT), allergic rhinitis (AR), and chronic rhinosinusitis (CRS).</p><p><strong>Conclusion: </strong>Current evidence suggests a genetic correlation between chronic rhinosinusitis and autoimmune diseases like allergic rhinitis, asthma, rheumatoid arthritis, hypothyroidism, and type 1 diabetes. Further research is required to elucidate the mechanisms underlying these associations.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in allergyPub Date : 2024-09-24eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1462579
Julie Stichova, Peter Slanina, Zita Chovancova, Jan Baros, Marek Litzman, Jiri Litzman, Marcela Vlkova
{"title":"Low CD46 expression on activated CD4<sup>+</sup> T cells predict improved Th1 cell reactivity to calcitriol in majority of patients with allergic eosinophilic asthma and healthy donors.","authors":"Julie Stichova, Peter Slanina, Zita Chovancova, Jan Baros, Marek Litzman, Jiri Litzman, Marcela Vlkova","doi":"10.3389/falgy.2024.1462579","DOIUrl":"https://doi.org/10.3389/falgy.2024.1462579","url":null,"abstract":"<p><strong>Background: </strong>Previous research showed that the intracellular complement system, with CD46 as its central molecule, regulates the Th1 response associated with IFN-γ production and transition to a type 1 regulatory response (Tr1) characterized by IL-10 production. This transition can be influenced by a vitamin D (calcitriol), favouring a shift towards Tr1 cells and increased IL-10 production, as described in some autoimmune diseases.</p><p><strong>Objective: </strong>It is unknown whether calcitriol modulates CD46-induced Th1 response towards regulatory type 1 T cells (Tr1) in allergic eosinophilic asthma and its value in relation to reducing inflammatory response.</p><p><strong>Methods: </strong>CD4<sup>+</sup> T cells from 58 patients with allergic eosinophilic asthma (AEA) and 49 healthy donors (HDs) were stimulated with αCD3/αCD46/IL-2 or αCD3/αCD46/IL-2/Calcitriol <i>in vitro</i> for 60 h and analyzed by flow cytometry. IFN-γ and IL-10 levels in cell culture supernatants were measured using ELISA.</p><p><strong>Results: </strong>CD4<sup>+</sup> T cells from patients with AEA demonstrated elevated CD46 expression in both the non-activated state and under stimulation conditions with αCD3/αCD46/IL-2 or αCD3/αCD46/IL-2/Calcitriol. Moreover, CD46 expression in AEA patients fluctuated with the pollen season, showing a significant increase during period of low pollen exposure. Calcitriol further induced CD4<sup>+</sup>Tr1 cells from <i>in vitro</i> generated CD4<sup>+</sup>Th1 cells in both HDs and AEA patients. However, in both cohorts were individuals (HDs: 35/49, AEA: 40/58) who responded to calcitriol with a more pronounced regulatory response. The calcitriol-induced regulatory effect manifested by a stronger surface decrease of CD46 on activated CD4<sup>+</sup> T cells (by 40% in HDs and by 26% in AEA), accompanied by a significant inhibition of IFN-γ and increased IL-10 production (by 31% in HDs and by 85% in AEA). These individuals were termed as the CD46D group. Contrary to this, calcitriol induced an increase in CD46 expression at the CD4<sup>+</sup> T cell surface in a minor group of HDs (14/49), and AEA patients (18/58), who were termed as the CD46I group. In CD46I group, CD4<sup>+</sup> T cells produced less IFN-γ in comparison with CD46D group (by 33% in HDs and by 43% in AEA) and were unable to upregulate IL-10 production following stimulation with αCD3/αCD46/IL-2/Calcitriol.</p><p><strong>Conclusion: </strong>Our results suggest the potential existence of a key for stratifying individuals suitable for calcitriol treatment in the context of low serum vitamin D levels. After validation in clinical studies, this key could be used as an adjunctive therapy not only for patients with allergic eosinophilic asthma, but also for other diseases.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in allergyPub Date : 2024-09-19eCollection Date: 2024-01-01DOI: 10.3389/falgy.2024.1453873
Nannan Jiang, Li Xiang, Huijie Huang, Xudong Zhang
{"title":"The management of exercise-induced anaphylaxis in a Chinese child with biologics: a case report.","authors":"Nannan Jiang, Li Xiang, Huijie Huang, Xudong Zhang","doi":"10.3389/falgy.2024.1453873","DOIUrl":"10.3389/falgy.2024.1453873","url":null,"abstract":"<p><p>Exercise-induced anaphylaxis (EIA) is a rare and potentially life-threatening disorder. In difficult to control and refractory cases of EIA, biologics such as omalizumab and dupilumab have shown promise, with documented successful outcomes. Here, we present a case of EIA with lipid transfer protein (LTP) sensitization successfully treated with omalizumab with long-term follow-up. A 12-year-old girl presented to our allergy department because of recurrent episodes of EIA, with no specific food ingestion before exercise. Allergen testing revealed sensitization to weed pollens, particularly mugwort (76.1 kUA/L) and <i>Alternaria alternata</i> (10.8 kUA/L). Allergen component testing indicated sensitization to LTP components from mugwort Art v 3 (49.9 kUA/L), wheat Tri a 14 (2.03 kUA/L), and peach Pru p 3 (11.5 kUA/L), with a negative result for omega-5 gliadin. Despite initial prophylactic treatment with budesonide-formoterol (80/4.5 μg) and cetirizine (10 mg) before exercise, the patient still experienced EIA; she was then recommended for dupilumab therapy (an initial dose of 600 mg, followed by 300 mg every 2 weeks for six doses). However, even while undergoing dupilumab therapy, she suffered two anaphylactic episodes after running 800-1,000 m. With the patient's consent, a trial of omalizumab was initiated (injections of 300 mg every 4 weeks). After 2 months of omalizumab therapy, the patient showed significant improvement. She had been engaging in physical exercise three times a week and experienced a mild episode of urticaria. There were no further episodes of anaphylaxis or emergency room visits. By the fourth month of omalizumab treatment, she was able to consume food normally even just before exercising and had returned to her full activity level without any restrictions. This case presents the first successful off-label use of omalizumab in the prevention of EIA in the Chinese population. It is concluded that omalizumab may be helpful in resolving EIA symptoms, as evidenced by this case of successful long-term use.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}