Immunogenetic HLA-DQ and IgG serological profiles in individuals with self-reported wheat/gluten sensitivity: a retrospective real-world evidence study

This is the authors' abstract. We don't add key points for this paper.

Introduction Many patients report adverse symptoms following wheat/gluten consumption. As “Self-Reported Wheat/Gluten Sensitivity” 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. Methods A retrospective observational study used Real-World Evidence (RWE) from 100 symptomatic individuals (2019–2024) 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 ( W=0.59, p<0.001 ). Consequently, inferential analyses included Chi-square ( X 2 ) tests for categorical associations, Spearman’s rank correlation ( r s ), and Odds Ratio (OR) calculations with 95% Confidence Intervals (95% CI). Results 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 ( X 2 = 10.24; p=0.001 ) and DQ3 ( X 2 = 4.84; p=0.028 ) were significant markers. Specific IgG reactivity occurred in 68% of cases, showing strong wheat-gluten correlation (r s =0.887; p<0.001 ) and extraordinary cross-reactivity ( OR=88.2; 95% CI: 25.8–301.4; p<0.001). Discussion 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.