Is Non-Celiac Wheat Sensitivity an Autoimmune Disorder?

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A recent study (P Mansueto et al. Am J Gastroenterol 2021; 116: 1015-1023. Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity). Thanks to Ben Gold for this reference.

The authors prospectively and consecutively studied 91 patients with Non-Celiac Wheat Sensitivity (NCWS) (F?M ratio 7:1); 76 healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls.

NCWS was diagnosed based on absence of celiac serology, absence of villous atrophy (while receiving a gluten-containing diet), negative IgE-testing for wheat allergy (either serum or skin prick tests) along with resolution of symptoms off wheat and symptom reappearance wiht a DBPC wheat challenge.

Key findings:

  • Twenty-three patients with NCWS (25.3%) presented with autoimmune diseases (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 = 0.002) and in patients with IBS (P = 0.05).
  • In the NCWS group, antinuclear antibodies tested positive in 71.4% vs HBD 19.7%, and vs patients with IBS 21.8% (P < 0.0001 for both).
  • The frequency of 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 = 0.0001 and P = 0.004, respectively).
  • Among NCWS with comorbid autoimmunity, duodenal lymphocytosis was present in ~80% and others had eosinophilic infiltration (~90%), both suggestive of ongoing immune activation. (Duodenal eosinophilic infiltration was also noted in ~60% of those who had absence of autoimmune disease too)

The associated editorial by Galipeau et al notes that only 16% of those who self-report as “gluten-sensitive” will actually fulfill the current consensus criteria for a diagnosis of NCWS. The diagnosis is problematic because of the absence of a validated biomarker. While the current study shows association with autoimmune markers, other studies have shown some have markers of immune activation and others with non-IgE-mediated food sensitivities.

My take: These type of studies help us understand NCWS. Yet, without a more definitive biomarker, many people will be on a gluten-free diet needlessly.

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