{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:55:20Z","timestamp":1764680120111,"version":"3.46.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Pediatric patients with beta-thalassemia (BT) face unique immunologic challenges due to chronic transfusions and viral exposure. Hepatitis C virus (HCV), a common infection in polytransfused individuals, may influence immune polarization. However, the combined effect of chronic HCV and host immunogenetics on allergic sensitization remains incompletely understood. Objective: To assess total serum IgE levels and allergic manifestations in HCV-positive vs. HCV-negative BT patients, and explore associations with common polymorphisms in IL10, TLR7, IL4, and IFNG genes Methods: This cross-sectional observational study enrolled 46 BT patients (37 HCV-positive, 9 HCV-negative) and 50 healthy controls. Clinical allergy history, total IgE levels (ELISA), and skin prick tests (SPT) for aeroallergens were collected. Genotyping for IL10 \u22121082, TLR7 rs179008, IL4 \u2212589, and IFNG +874 polymorphisms was performed. Associations between genotypes, HCV status, and IgE levels were analyzed descriptively due to small sample size Results: HCV-positive BT patients had lower mean IgE levels (18.73 \u00b1 4.2 IU\/mL) and fewer reported allergic symptoms (21.6%) compared to HCV-negative counterparts (118.76 \u00b1 7.9 IU\/mL; 55.5%). The IL10 \u22121082 AA and TLR7 rs179008 TT genotypes were more common in the HCV-positive group and were associated with lower IgE levels. No associations were noted for IL4 or IFNG variants. Splenectomy appeared to further modify IgE levels in HCV-negative patients. Due to limited power and absence of multivariate analysis, findings are exploratory. These preliminary observations may inform future studies of immune deviation in chronically infected pediatric cohorts. Conclusions: Chronic HCV infection may contribute to immune tolerance and reduced allergic expression in BT patients, potentially modulated by IL10 and TLR7 genotypes. Further studies with functional immune profiling and larger cohorts are required.<\/jats:p>","DOI":"10.3390\/genes16121440","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:39:43Z","timestamp":1764679183000},"page":"1440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Host Immunogenetics and Chronic HCV Infection Shape Atopic Risk in Pediatric Beta-Thalassemia: A Genotype\u2013Phenotype Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Caterina","family":"Cuppari","sequence":"first","affiliation":[{"name":"Pediatric Emergency Unit, Department of Maternal and Child Health, University Hospital of Messina, \u201cG. Martino\u201d Policlinic, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cGaetano Barresi\u201d, University of Messina, \u201cG. Martino\u201d Policlinic, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Colavita","sequence":"additional","affiliation":[{"name":"Pediatric Emergency Unit, Department of Maternal and Child Health, University Hospital of Messina, \u201cG. Martino\u201d Policlinic, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8720-5267","authenticated-orcid":false,"given":"Clelia","family":"Cusmano","sequence":"additional","affiliation":[{"name":"Pediatric Emergency Unit, Department of Maternal and Child Health, University Hospital of Messina, \u201cG. Martino\u201d Policlinic, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1575-1905","authenticated-orcid":false,"given":"Valeria","family":"Tallarico","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1955-8074","authenticated-orcid":false,"given":"Valerio","family":"Caruso","sequence":"additional","affiliation":[{"name":"Psychiatry 2 Unit, Clinical and Experimental Medicine Department, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9143-4637","authenticated-orcid":false,"given":"Roberto","family":"Chimenz","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology and Dialysis Unit, University Hospital \u201cG. Martino\u201d, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mimma","family":"Caloiero","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Lamezia Terme Hospital, 88046 Lamezia Terme, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariarosa","family":"Calafiore","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Polistena Hospital, 89024 Polistena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonina","family":"La Mazza","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adulthood and Childhood \u201cG. Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1774-8173","authenticated-orcid":false,"given":"Luciana","family":"Rigoli","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adulthood and Childhood \u201cG. Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.hoc.2009.11.006","article-title":"Update on Thalassemia: Clinical Care and Complications","volume":"24","author":"Cunningham","year":"2010","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1182\/blood-2003-09-3167","article-title":"Thalassemia Clinical Research Network. 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