INTRODUCTION: Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestationsconsequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studiesinvestigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate thefrequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS.METHODS: Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a singlecenter, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis ofirritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels weremeasured. Human leukocyte antigen haplotypes were determined, and duodenal histology performedin all patients carrying the DQ2/DQ8 haplotypes. Participants completed a questionnaire, and theirmedical records were reviewed to identify those with ADs.RESULTS: Twenty-three patients with NCWS (25.3%) presented with ADs; autoimmune thyroiditis (16 patients,17.6%) was the most frequent. The frequency of ADs was higher in patients with NCWS than in HBD(P 5 0.002) and in patients with IBS (P 5 0.05). In the NCWS group, antinuclear antibodies testedpositive in 71.4%vsHBD19.7%, and vs patients with IBS 21.8% (P < 0.0001 for both). The frequencyof extractable nuclear antigen antibody (ENA) positivity was significantly higher in patients with NCWS(21.9%) than in HBD (0%) and patients with IBS (3.6%) (P 5 0.0001 and P 5 0.004, respectively).Among the patients with NCWS, 9.9% tested positive for antithyroglobulin, 16.5% for antithyroidperoxidase, and 14.3% for antiparietal cell antibodies; frequencies were not statistically different fromcontrols. The presence of ADs was related to older age at NCWS diagnosis, female sex, duodenallymphocytosis, and eosinophil infiltration.DISCUSSION: One in 4 patients withNCWS suffered from AD, and serum antinuclear antibodies were positive in a veryhigh percentage of cases. These data led us to consider NCWS to be associated to ADs.