High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies

Gastroenterology. 2015 Sep;149(3):596-603.e1. doi: 10.1053/j.gastro.2015.05.040. Epub 2015 May 27.


Background & aims: There is much interest in wheat sensitivity among people without celiac disease (CD), but little is known about any risks associated with the condition. We evaluated the prevalence of autoimmune diseases (ADs) among patients with nonceliac wheat sensitivity (NCWS), and investigated whether they carry antinuclear antibodies (ANA).

Methods: We performed a retrospective study of 131 patients diagnosed with NCWS (121 female; mean age, 29.1 years) at 2 hospitals in Italy from January 2001 through June 2011. Data were also collected from 151 patients with CD or irritable bowel syndrome (IBS) (controls). Patient medical records were reviewed to identify those with ADs. We also performed a prospective study of 42 patients (38 female; mean age, 34 years) diagnosed with NCWS from July 2011 through March 2014 at 3 hospitals in Italy. One hundred age- and sex-matched subjects with CD or IBS served as controls. Serum samples were collected from all subjects and ANA levels were measured by immunofluorescence analysis. Participants completed a questionnaire and their medical records were reviewed to identify those with ADs.

Results: In the retrospective analysis, similar portions of subjects with NCWS (29%) and CD (29%) developed ADs (mainly Hashimoto's thyroiditis, 29 cases), compared with a smaller proportion of subjects with IBS (4%) (P < .001). In the prospective study, 24% of subjects with NCWS, 20% of subjects with CD, and 2% of subjects with IBS developed ADs (P < .001). In the retrospective study, serum samples tested positive for ANA in 46% of subjects with NCWS (median titer, 1:80), 24% of subjects with CD (P < .001), and 2% of subjects IBS (P < .001); in the prospective study, serum samples were positive for ANA in 28% of subjects with NCWS, 7.5% of subjects with CD (P = .02), and 6% of subjects with IBS (P = .005 vs patients with NCWS). ANA positivity was associated with the presence of the HLA DQ2/DQ8 haplotypes (P < .001).

Conclusions: Higher proportions of patients with NCWS or CD develop autoimmune disorders, are ANA positive, and showed DQ2/DQ8 haplotypes compared with patients with IBS.

Keywords: Celiac Disease; Food Allergy; Gluten Sensitivity; Immune Response.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Antinuclear / blood*
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / epidemiology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Biomarkers / blood
  • Celiac Disease / blood
  • Celiac Disease / diagnosis
  • Celiac Disease / epidemiology
  • Celiac Disease / genetics
  • Celiac Disease / immunology*
  • Female
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology
  • Haplotypes
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Prevalence
  • Prospective Studies
  • Retrospective Studies
  • Risk Factors
  • Wheat Hypersensitivity / blood
  • Wheat Hypersensitivity / diagnosis
  • Wheat Hypersensitivity / epidemiology
  • Wheat Hypersensitivity / genetics
  • Wheat Hypersensitivity / immunology*


  • Antibodies, Antinuclear
  • Biomarkers
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen