1st order laboratory parameters – obligatory laboratory tests.
- Small blood count to exclude iron deficiency anemia [microcytic hypochromic anemia:
- MCV↓ → microcytic
- MCH ↓ → hypochromic]
- Ferritin (iron storage protein) [ferritin ↓]
- Alanine aminotransferase (ALT, GPT), aspartate aminotransferase (AST, GOT), gamma-glutamyl transferase (γ-GT, gamma-GT; GGT) [in up to 50% of cases: elevated transaminases].
- Detection of gliadin antibodies of the IgA and IgG type. [these laboratory parameters are increasingly losing importance; antibodies against native gliadin have only a low positive predictive value: 18-31%]These antibody determinations are also suitable for monitoring the course under a gluten-free diet, since with increasing duration of therapy, their concentrations fall below the detection limit.
- Celiac disease serology* : Transglutaminase antibody (tTG) or endomysium antibody (EMA)/endomysium IgA and transglutaminase IgA.
- Transglutaminase IgA antibodies (English : tissue transglutaminase, abbreviated tTG- Ak): sensitivity (percentage of diseased patients in whom the disease is detected by the use of the test, i.e., a positive test result occurs) 74-100%, specificity (probability that actually healthy persons who do not suffer from the disease in question are also detected as healthy in the test) 78-100%.
- Endomysium antibody (EMA): sensitivity 83-100%, specificity 95-100%; there is an association between the titer level and the degree of villous atrophy.
- Selective IgA deficiency (determination of total IgA) must be excluded beforehand (prevalence (disease frequency) 2%); because in the presence of IgA deficiency* endomysium and transglutaminase IgA antibodies may not be detectable.
- IgG antibodies against deamidated gliadin peptides (IgG anti-DGP), which are formed after deaminidation by tissue transgluatminase (TG2) in the small intestinal mucosa (mucosa) in celiac disease – in cases of proven IgA deficiency and suspected celiac disease [predictive value: < 70%].
- IgA (total IgA in serum) – see above under celiac disease serology.
* Duodenal biopsy may be omitted if the following conditions are met [European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guideline]:
- Anti-TG (transglutaminase) IgA [>10-fold above the normal limit].
- Endomysium antibody (EMA) titer [positive in a second, separately drawn blood sample]
Laboratory parameters 2nd order – depending on the results of the history, physical examination, etc. – for differential diagnostic clarification.
- Exclusion of malabsorption
- Genetic testing (DNA analysis)/detection of celiac disease-associated HLA-DQ gene constellation (Caveat: Gene Diagnostics Act)* :
- HLA-DQ2 heterodimer in cis-configuration (HLA-DR3-DQA1* 0501-DQB1* 0201) or in trans-configuration (HLA-DR5-DQA1* 0505- DQB1* 0301 respectively and DR7-DQA1* 0201-DQB1* 0202) and.
- HLA-DQ8 heterodimer (HLA-DR4-DQA1* 0301- DQB1* 0302).
[30-35-40% of the total population is HLA-DQ2 or DH8 positive; only about 2% of these individuals will develop celiac disease during their lifetime; nearly 100% of celiac disease sufferers are positive for HLA-DQ2 and/or -DQ8]
* The genetic test excludes celiac disease (to the greatest extent possible) if negative and, if positive, offers the option of confirming celiac disease without a biopsy if the following conditions are met:
- Classic (gastrointestinal) manifestation.
- Transglutaminase (TG2) IgA titers elevated 10-fold above the cutoff value.
- Confirmation of seropositivity by positive endomysium antibody (≥ 1: 5).
- Education of parents about the advantages and disadvantages of duodenal biopsy (by a pediatric gastroenterologist).
- Clinical and serologic remission on a gluten-free diet.
Further notes
- After a confirmed diagnosis of celiac disease, a blood test for antibodies (see above) in family members is recommended to possibly find out affected persons with subclinical celiac disease.
- For evaluation of a gluten-free diet, the tTG-IgA-Ak (IgA autoantibodies against tissue transglutaminase) is suitable: a persistently elevated titer is highly suspicious of persistent dietary failure.
- Immunohistochemical findings and clonality analysis of the T-cell receptor gene are critical to distinguish refractory celiac disease type I (autoimmune character) vs type II (prelymphoma character).
Celiac disease screening [S2k guideline]
The 1st-degree family members (parents, children, siblings) of celiac disease sufferers should be offered antibody diagnostics even if they do not have typical symptoms.
- In children and adolescents: Diagnostics every 1-2 years and should be repeated if celiac disease-associated symptoms occur (see “Symptoms – Complaints” below).
- In adults: one-time testing; further times only if celiac disease-associated symptoms.
