Gluten Sensitivity

Adapted from [92,93]

†Antibody testing is only accurate if the person's diet contains gluten for at least 1–6 months (varies by source) prior to testing. The amount of time is based on current practice and has not been firmly established through evidenced-based research.
‡ATA or anti-tTG released from damaged intestine during active disease. The intestinal T-cell response to a-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase.
§EMAs detect antibodies to tissue transglutaminase. Replaced by ATA or anti-tTG.
¶Tests for deamidated gliadin antibodies are considered experimental by Aetna. IgG DPGs and AGAs appear to have specificity for celiac disease and gluten sensitivity, as well as for cerebellar ataxia without intestinal involvement.
#IgG AGAs no longer routinely recommended because of their lower sensitivity and specificity: approximately 50% for both celiac disease and gluten sensitivity. Recommended that this test be abandoned and replaced by ATAs or anti-tTG. However, ATA or anti-tTG and EMA are inaccurate in infants, so AGA are ordered.
††Most patients with celiac disease are HLA-DQ2(+), with the remaining few expressing HLA-DQ8. These two class II molecules present gluten peptides to the gluten-specific T cells found only in the gut of celiac disease patients, but not controls. Karell et al. noted that approximately 6% of adult celiac patients with villous atrophy did not express a DQ2 or DQ8 haplotype [94].
‡‡Celiac disease is patchy so at least four to five biopsy specimens should be obtained, including samples from the duodenum's more distal segments and bulb area. Pathologists experienced in celiac disease detection are recommended.
Approximately 10% of celiac disease patients are IgA deficient, so both IgA and IgG should be used along with total IgA to determine whether there is an IgA deficiency.
AGA: Antigliadin antibody; Anti-tTG: Autoantibodies against the transglutaminase protein; ATA: Antitissue transglutaminase antibodies; DGP: Deamidated gliadin antibody; EMA: Anti-endomysial antibody.
Adapted from [92,95]. © 2011 Amy Brown.

tG: Transglutaminase.
© 2011 Amy Brown.

^†Less than half of newly diagnosed celiac patients exhibit classic gastrointestinal symptoms.
Adapted from [64,92,93,99–103].
© 2011 Amy Brown.

Adapted from [93] and references noted above.

Authors and Disclosures

Amy C Brown
Department of Complementary and Alternative Medicine, John A Burns School of Medicine, University of Hawaii, 651 Ilalo Street, MEB 223, Honolulu, HI 96813, USA.

Tel.: +1 808 692 0907 amybrown@hawaii.edu

Sidebar

Key Issues

• Gluten sensitivity requires research to clarify its definition, diagnostic criteria, laboratory tests and appropriate treatments.

• The environmental factor(s) behind what appears to be increasing anecdotal reports of gluten sensitivity need to be deciphered quickly as more and more people appear to be affected.

• Gluten sensitivity should be discussed in the medical school curriculum as a possible emerging problem in need of more evidence-based information.

• Patients testing negative for celiac disease who still experience gastrointestinal symptoms after gluten ingestion should undergo a gluten-free diet, or better yet, an elimination diet to determine whether diet is a factor. A monitored, blinded challenge would eliminate the placebo effect.

• Gluten sensitivity needs to be taken more seriously by clinicians as a possible cause of digestive problems, and immediately addressed, as it is unknown whether the consequences of untreated celiac disease also affect those with gluten sensitivity.

• It is suggested that gluten sensitivity be screened for in individuals susceptible for celiac disease.

• Strict adherence to a gluten-free diet should be emphasized to celiac disease patients. They may possibly avoid some of the more serious side effects such as infertility, premature births, cancer, autoimmune-related conditions and brain calcification. Both celiac disease and gluten-sensitive patients should be informed of these side effects, but the latter should be told that research has not yet confirmed if they too are susceptible.