{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:04:12Z","timestamp":1789653852951,"version":"4.0.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The pathogenesis of pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasingly recognized as an immunometabolic process driven by chronic low-grade inflammation (metainflammation). While nutritional surplus and visceral adiposity are established primary drivers, the contribution of underlying subclinical host immune variations remains largely unexplored. This mini-review investigates the intersection between childhood obesity and subclinical humoral immune dysfunctions, specifically variants of Common Variable Immunodeficiency (CVID). We propose that subtle defects in adaptive immunity\u2014such as partial secretory IgA or IgG subclass deficiencies\u2014compromise mucosal barrier integrity, triggering a breakdown of the gut-liver axis. This barrier failure allows an influx of pathogen-associated molecular patterns (PAMPs) into the portal circulation, overwhelming hepatic immune tolerance. Within the liver, this persistent microbial exposure primes Toll-like receptor pathways and activates the NLRP3 inflammasome within Kupffer cells, accelerating hepatocyte pyroptosis and tissue damage. Concurrently, the T-cell dysregulation characteristic of CVID variants interacts with hepatic lipotoxicity, changing the disease phenotype from simple steatosis to aggressive tissue remodeling. Identifying these subclinical immunodeficiencies in progressive pediatric MASLD is essential for developing personalized, targeted immunometabolic therapies for at-risk youth.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1930909","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:26:02Z","timestamp":1789651562000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The immunogenic cross-talk in pediatric MASLD: does subclinical immune dysfunction accelerate early hepatic destruction?"],"prefix":"10.3389","volume":"17","author":[{"given":"Harald","family":"Mangge","sequence":"first","affiliation":[{"name":"Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz","place":["Graz, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1159\/000525543","article-title":"Nonalcoholic fatty liver disease in children with obesity: Narrative review and research gaps","volume":"95","author":"Furthner","year":"2022","journal-title":"Horm Res Paediatr"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.122466","article-title":"Primary immunodeficiency disorders: Antibody deficiencies","volume":"109","author":"Ballow","year":"2002","journal-title":"J Allergy Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27031518","article-title":"Liver disease in common variable immunodeficiency: Current 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