Celiac disease Gluten allergy IgA and IgG Transglutamine
For gluten allergy, 3 tests are done in the blood test:
- transglutaminase (tTG), tissue (IgA) serum
- transglutaminase (tTG), tissue IgG serum
- IgA serum
About Celiac Disease
Celiac disease is more common than previously thought.
More than half of celiac patients do not have the classic picture of diarrhea. There may also be anemia and decreased bone density.
Celiac disease is a chronic intestinal disease induced by a hypersensitivity to the storage proteins of cereals (gluten). The hypersensitivity specifically involves the gluten of related species such as wheat, barley and rye, but not oats, rice or corn. Celiac disease has always been considered a fairly rare condition, but with the development of blood tests, it appears to be much more common.
In young children, the typical presentation is in the form of diarrhea and a bloated abdomen. There is also delayed growth. However, vomiting, anorexia and constipation may also be the first symptoms.
In adults, the picture is less pronounced. Chronic diarrhea, flatulence and weight loss can be associated with celiac disease. However, more than 50% of coeliacs do not have diarrhoea but milder symptoms such as abdominal pain. Of the patients who do not have abdominal symptoms, most appear to have anemia. other consequences may include decreased bone density, infertility, neurological symptoms (muscle disease, drunkenness or epilepsy) or dermatitis herpetiformis (itchy skin) . Celiac disease is associated with conditions such as diabetes mellitus type 1, Down syndrome, and thyroid disorders.
In the case of TTG transglutaminase IGG and IGA, total IGA should always be determined to rule out a systematic IgA deficiency that could cause false negative gluten allergy.
Guidelines on when to request which test
Sensible Diagnostics Considerations in screening blood tests for celiac disease Celiac disease is a hypersensitivity reaction of the body against gluten (gluten is found in almost all grain products). In the process, the body produces antibodies. These antibodies and auto-reactive T-cells destroy the intestinal villi (villi atrophy), which results in poorer absorption of nutrients.
When following a gluten-free diet, the intestine recovers completely and the antibodies disappear. The antibodies (including IgA antibodies to tissue transglutaminase (anti-TTG IgA), deamidated gliadin peptide and endomysium) can be used in making the diagnosis.
1. For screening for celiac disease, request anti-TTG IgA and total IgA.
For screening for celiac disease, we look for the presence of IgA antibodies to tissue transglutaminase. The antibodies made in the gastrointestinal tract are usually of the IgA class. However, 1 in 700 individuals is (symptomless) IgA-deficient and celiac patients are more often IgA deficient.
Therefore, in case of a negative result of the anti-TTG (below the laboratory reference values), a false negative result must be excluded. Therefore, the IgA content is also determined. IgA deficiency is defined as IgA < 0.07 g/L. With an IgA <0.07 g/L, it is common to determine additional IgG antibodies to TTG.
Determination of IgG antibodies (against tissuetransglutaminase and endomysium) is useful only in patients with IgA deficiency.
2. On suspicion of celiac disease, do not request the anti-endomysium IgA or anti-deamidated gliadin peptide
The anti-TTG IgA is the antibody of choice for diagnosis and follow-up. The height of the titer correlates with the severity of the villous atrophy.
Only in children under 2 years of age can the anti-TTG be (false) reduced or negative.
If there is a strong suspicion of celiac disease, it is then advisable to request antibodies against deamidated gliadin peptide.
IgA antibodies to endomysium are only performed as a confirmatory test in the presence of anti-TTG antibodies. Thus, they do not need to be requested immediately at initial screening.
The test for antibodies to endomysium detects the same antibodies as the anti-TTG test, but using a different (indirect immunofluorescence) technique.
3. Do not apply for anti-TTG IgA for celiac disease screening when already on a low gluten diet
When celiac disease is suspected and the patient in question already avoids gluten in the diet, the body is not adequately exposed to gluten and the likelihood of antibody formation is reduced. For confirmation of the diagnosis, it is important that patient remains exposed to gluten. Depending on antibody formation, antibody positivity can usually be found again 3 weeks after gluten use.
When following up patients with a diagnosis of celiac disease, the response to the diet can be monitored using the anti-TTG IgA. The concentration of antibodies will decrease if the gluten-free diet is maintained
4. Do not request DNA testing for HLA-DQ2 and DQ8 when celiac disease is suspected.
Of patients with celiac disease, 98% have the HLA-DQ2 and/or HLA-DQ8 genotype. Absence of this genotype virtually rules out sensitivity to gluten. However, 40% of the population is positive for HLA-DQ2/8. Therefore, this examination has no added value as a screening test for suspected celiac disease. In groups at increased risk of celiac disease (Down syndrome, positive family history, Diabetes Mellitis type I, autoimmune thyroid disease), frequent serological testing can be avoided when the HLA-DQ2.2 and HLA-DQ2.5 and HLA-DQ8 genotype is absent. Only in high-risk groups is genotyping screening recommended as a substitute for repeated serologic testing.
In children with high anti-TTG IgA (at least 10x above cutoff value) and a positive endomysial test, a biopsy can be avoided for the definitive diagnosis of celiac disease if they have the HLA-DQ2 and/or HLA-DQ 8 genotype. In adults, a small intestine biopsy is the gold standard for the time being.
References: CBO/MDL guideline 2008: Guideline Celiac Disease and Dermatitis Herpetiformis Husby S., Koletzko S., Korponay-Szabó I. R., et al; ESPGHAN Guidelines for the diagnosis of celiac disease in children and adolescents: An evidencebased approach. J pediatr Gastroenterol nutr. 2012 Jan; 54(1): 136-160. Dahlbom I1 , Korponay-Szabó IR, Kovács JB, Szalai Z, Mäki M, Hansson T. Prediction of clinical and mucosal severity of coeliac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase. J Pediatr Gastroenterol Nutr. 2010 Feb;50(2):140- 6. C Lagerqvist, I Dahlbom, T Hansson, et al. Anti-gliadin Immunoglobulin A Best in Finding Celiac Disease in Children Younger Than 18 Months of Age. JPGN 47:428-435, 2008. P. Hill & G Holmes. Coeliac disease: a biopsy is not always necessary for diagnosis. Aliment Pharmacol Ther. 2008; 27: 572-577 PG Hill and SA McMillan. Anti-tissue transglutaminase antibodies and their role in the investigation of coeliac disease. Ann Clin Biochem 2006; 43: 105-117 P.H.R. Green and C. Cellier. Celiac Disease N Engl J Med 2007;357:1731-43. Damoiseaux JGMC, Damoiseaux RAMJ. Celiac disease diagnostics in the general practitioner. GP Law 2005;48(1):24-7.