eng Science and Education Publishing International Journal of Celiac Disease 2334-3486 2024-12-22 12 1 33 40 10.12691/ijcd-12-1-7 IJCD20241217 article Michael F. Roberts mrobert@linfield.edu 1 Nadine Grzeskowiak 2 Stephen E. Bricher 3 Department of Biology, Linfield University, McMinnville, Oregon 97128 USA Celiac Nurse Consulting, Salem, Oregon 97302 USA Department of Mathematics and Computer Science, Linfield University, McMinnville, Oregon 97128 USA We investigated gluten-related disorders (GRD) in intestinal biopsy-proven subjects to determine the relation between genotype (i.e., Human Leukocyte Antigen (HLA) DQ alleles) and phenotype (i.e., antibody levels and clearly defined symptoms). Subjects had known DQ genotypes, information on IgA anti-Endomysial antibodies (EMA) and/or anti-tissue Trans Glutaminase (tTG) antibodies (tTGA). Subjects also answered a survey characterizing gastrointestinal, skin, and neural symptoms. Though all were biopsy-proven, HLA genotypes included all combinations of DQ2.5, DQ2.2, DQ8, DQ7.5, DQ5, and DQ6. Subject antibody levels were proportional to the number of DQ2.5 haplotypes, and subjects with non-CD-associated haplotypes did not have positive antibody scores (despite positive biopsy). In addition, the total number of GRD-associated symptoms were approximately the same across all genotypes. The results suggest that gluten damage and symptoms are independent of genotype; i.e., not restricted to people with DQ2.5, DQ2.2, or DQ8 genotypes or to those with positive antibody scores. We propose a GRD classification in which clinicians consider GRD symptoms and signs even in people without CD-associated genotypes, as these likely make up the majority of those with gluten-related disorders. https://pubs.sciepub.com/ijcd/12/1/7/ijcd-12-1-7.pdf gluten-related disorders celiac disease innate and acquired immune responses IgA tTGA and EMA antibodies gluten-related symptoms