Objective:

To characterize the immunogenetic and serological profiles of a clinical cohort with self-reported wheat/gluten sensitivity (SRWGS) and analyze the frequency of HLA-DQ alleles and their association with specific IgG antibody reactivity, highlighting the significance for clinical management.

Key Findings:

• 100% cumulative frequency of HLA-DQ susceptibility variants observed, indicating a potential genetic predisposition.
• HLA-DQ1 (56%), DQ2 (54%), DQ3 (40%), and DQ8 (33%) were the prevalent variants, suggesting a diverse genetic landscape.
• DQ8 and DQ3 were significant markers (p<0.001 and p=0.028 respectively), which may inform clinical assessments.
• 68% of cases showed specific IgG reactivity with strong correlation to wheat-gluten (rs=0.887; p<0.001), indicating a robust immune response.
• IgG cross-reactivity indicated a strong association with wheat/gluten (OR=88.2; 95% CI: 25.8–301.4; p<0.001), supporting the need for targeted dietary interventions.

Interpretation:

The findings suggest a consistent genetic background in symptomatic individuals that exceeds prevalence in the general Western population, indicating potential immune activation and the need for tailored clinical approaches.

Limitations:

• Non-probabilistic convenience sampling may limit generalizability and introduce selection bias.
• Retrospective design may introduce bias in data collection, particularly in self-reported symptoms.

Conclusion:

Characterizing the biological profiles of individuals with self-reported wheat/gluten sensitivity is crucial for advancing precision management and biomarker-informed interventions, and further research is needed to validate these findings.