{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:03:56Z","timestamp":1779685436769,"version":"3.53.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"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":"\n Introduction<\/jats:title>\n Many patients report adverse symptoms following wheat\/gluten consumption. As \u201cSelf-Reported Wheat\/Gluten Sensitivity\u201d lacks gold-standard biomarkers, characterizing biological profiles in Western populations is essential for precision management. This study analyzes immunogenetic (HLA-DQ) and serological (IgG) patterns in a real-world clinical cohort.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A retrospective observational study used Real-World Evidence (RWE) from 100 symptomatic individuals (2019\u20132024) selected via non-probabilistic convenience sampling. Participants underwent HLA-DQ genotyping and serum IgG reactivity testing for wheat\/gluten via a validated ELISA-based assay. Data normality was formally assessed using the Shapiro-Wilk test, revealing a non-parametric distribution (\n W=0.59, p&lt;0.001<\/jats:italic>\n ). Consequently, inferential analyses included Chi-square (\n X<\/jats:italic>\n 2<\/jats:sup>\n ) tests for categorical associations, Spearman\u2019s rank correlation (\n \n r\n s<\/jats:sub>\n <\/jats:italic>\n ), and Odds Ratio (OR) calculations with 95% Confidence Intervals (95% CI).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A 100% cumulative frequency of HLA-DQ susceptibility variants was observed. The immunogenetic landscape revealed complex heterozygosity: DQ1 was most prevalent (56%), followed by DQ2 (54%), DQ3 (40%), and DQ8 (33%). DQ8 (\n \n X\n 2<\/jats:sup>\n \u00a0=\u00a010.24; p=0.001\n <\/jats:italic>\n ) and DQ3 (\n \n X\n 2<\/jats:sup>\n \u00a0=\u00a04.84; p=0.028\n <\/jats:italic>\n ) were significant markers. Specific IgG reactivity occurred in 68% of cases, showing strong wheat-gluten correlation\n \n (r\n s<\/jats:sub>\n =0.887; p&lt;0.001\n <\/jats:italic>\n ) and extraordinary cross-reactivity (\n OR=88.2; 95% CI: 25.8\u2013301.4; p&lt;0.001).<\/jats:italic>\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n Findings reveal a ubiquitous HLA-DQ frequency, suggesting a consistent genetic background in symptomatic individuals that significantly exceeds prevalence in the general Western population. This enriched 'mosaic' may facilitate immune activation. Furthermore, the observed IgG cross-reactivity validates the 'wheat\/gluten complex' as a synchronized immunological unit, supporting a transition toward biomarker-informed nutrition in real-world settings.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1814097","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:44:18Z","timestamp":1779684258000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunogenetic HLA-DQ and IgG serological profiles in individuals with self-reported wheat\/gluten sensitivity: a retrospective real-world evidence study"],"prefix":"10.3389","volume":"17","author":[{"given":"Andreina","family":"White","sequence":"first","affiliation":[{"name":"Universidad Central de Venezuela (UCV)","place":["Caracas, Venezuela"]},{"name":"Autonomous University of Barcelona","place":["Barcelona, Spain"]},{"name":"University of Barcelona","place":["Barcelona, 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Venezuela"]},{"name":"Regis College","place":["Weston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"White","sequence":"additional","affiliation":[{"name":"Department of Assistance and Nutrition, School of Nutrition and Dietetics, Faculty of Medicine, University of Los Andes (ULA)","place":["M\u00e9rida, Venezuela"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milaidi","family":"Garc\u00eda Bravo","sequence":"additional","affiliation":[{"name":"Department of Assistance and Nutrition, School of Nutrition and Dietetics, Faculty of Medicine, University of Los Andes (ULA)","place":["M\u00e9rida, Venezuela"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-10-13","article-title":"Spectrum of gluten-related disorders: consensus on new nomenclature and 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