Table 4.

Differences between CD, NCGS, and wheat allergy.

Terms	CD	NCGS	Wheat allergy
Definition	Autoimmune disorder due to intolerance to gluten proteins	Disorder due to gluten proteins, FODMAPS in food, ATIs in wheat. Different from CD and wheat allergy	Allergic reaction to wheat containing foods through food ingestion, contact, inhalation of flour dust
Reaction time	Slow (30 min to 24 h)	Slow (several hours)	Immediate
Epidemiology	Affects roughly 1% of population	Affects 0.6–6% of population	0.5–9% in children, 0.2–1% in adults
Antigen	Gliadins from gluten	Gluten proteins, ATIs, FODMAPS	ATIs, Gliadins, Peroxidase, Thiol reductase
Immune response activation	Both innate and adaptive immune response	Innate immune response	IgE mediated immune response
	Deamination by enzyme T2G	No such involvement of enzyme studies till date
	Activation of inflammatory cytokines like IFN-γ	No such activation
Hallmark	Lymphocytic duodenosis	Functional dyspepsia, Lymphocytic duodenosis in some cases only	Type I and Type IV hypersensitivity
	IEL levels increased->25/100 enterocytes	In Functional dyspepsia, no increase in IELs but increase in duodenal eosinophils
HLA genotyping (HLA DQ2 and DQ-8)	Present in 95% of patients	Present/absent, 50% of patients	Not used
Serological analysis
Anti-T2G antibody	Positive	Negative	No need
Anti-EM antibody	Positive	Negative	No need
Anti-gliadin antibody	Positive	Positive	No need
Anti-deaminated gliadin peptide	Positive	Negative	No need
Ig E antibodies	No need	No need	Positive (Wheat specific IgE)
Histological response	Villous atrophy with crypt hyperplasia	Mildly inflamed mucosa, activated circulating basophils	None
Duodenal biopsy	Positive, MARSH type 3	Negative, MARSH type 0 or 1	No need
IBS indication	Absent/ less prevalent than NCGS	Overlapping with IBS, with 48% of patients affected	Absent
Skin Prick test	No need	No need	Positive
Symptoms Intestinal	Chronic diarrhea, weight fluctuation, weakness, fatty stools, abdominal bloating	Diarrhea, weight loss, gas	Diarrhea and vomiting immediately after wheat ingestion
Extra-intestinal	Infertility, thyroiditis, muscle cramps, delayed growth, iron deficiency anemia	Glossitis, leg and arm numbness, headache, anemia, dermatitis, tiredness, foggy mind, depression, anxiety	Exercise induced anaphylaxis, Atopic dermatitis, Urticaria, Chronic asthma and rhinitis.
GFD	Effective control	Partially effective	Partially effective
Overlap with other autoimmune illness	Increased prevalence Type I diabetes-5% Autoimmune thyroiditis-19%	Not so common Type I diabetes-not found Autoimmune thyroiditis-1.3%	–
Treatment	Following GFD	Avoidance of gluten, FODMAPS in diet (Gluten challenge)	Avoidance of wheat (contact, ingestion, inhalation)