Limited role of HLA DQ2/8 genotyping in diagnosing coeliac disease

Abstract

The European guidelines for diagnosing coeliac disease in children were revised in 2012. These recommend that in symptomatic children, a diagnosis of coeliac disease can be made without small-bowel biopsies provided their anti-tissue transglutaminase (anti-tTG) titre is >10 times of upper-limit-of-normal (>10×ULN) and anti-endomysial antibody is positive. In order to firm up the diagnosis in these children with very high anti-tTG titre, HLA-DQ2/DQ8 should be checked and be positive. Approximately 25-40% of white Caucasian population has HLA-DQ2/DQ8 haplotype. However, only 0.1-1% of the population will develop coeliac disease. Therefore, HLA-DQ2/DQ8 testing must not be done to 'screen' or 'diagnose' children with coeliac disease. Its use by paediatricians should be limited to children with anti-tTG>10×ULN, where the diagnosis of coeliac disease is being made on serology alone. A review of case referrals made to a tertiary paediatric gastroenterology centre in Southwest England demonstrated that HLA-DQ2/DQ8 testing is being requested inappropriately both in primary and secondary care suggesting a poor understanding of its role in diagnosis of coeliac disease. This article aims to clarify the role of HLA-DQ2/DQ8 testing for clinicians working in non-specialist settings.

Serum transglutaminase antibodies do not always detect the persistent villous atrophy in patients with celiac disease on a gluten-free diet

“…Symptoms and signs of celiac disease are both intestinal and extra-intestinal [2,5,17,18], and many patients with celiac disease have no symptoms [2,5]. Regarding genetic predisposition, the HLA-DQ2 heterodimer is present in more than 95% of celiac patients, whereas HLA-DQ8 is present in the other 5% of celiac patients [2,5,16]. The presence of HLA-DQ2 or HLA-DQ8 is necessary but not sufficient for celiac disease diagnosis, as HLA-DQ2 is present in 30-40% of the general population, whereas only 1% of subjects will develop celiac disease [2,5,16].…”

“…Then, in the diagnostic flow chart of celiac disease, the typing for HLA-DQ2 and HLA-DQ8 is very important for its high negative predictive value, as celiac disease is very unlikely in the absence of HLA-DQ2 and HLA-DQ8 [2,5,16,19]. Celiac disease probability in subjects with the positivity of tTGs and EMAs is very high; in this case, the UGIE with the histological evaluation of the duodenal biopsies is necessary to confirm the celiac disease in adult patients [2,5,6,15].…”

“…The serology evaluation includes antitissue transglutaminase antibodies (tTGs), endomysial antibodies (EMAs) and deamidated gliadin peptide antibodies (DGPs). The genetic evaluation includes typing for HLA-DQ2 and HLA-DQ8 haplotypes [5,16]. The histological evaluation assesses the tissue changes in the duodenal mucosa and is currently graded by Marsh criteria [5].…”

Non-celiac gluten/wheat sensitivity: still more questions than answers

“…Oproti celiakii však u NCG/PS nebyla prokázána silná asociace s geny HLA DQ2/8 [16]. HLA DQ2/8 jsou přítomny až u 99 % pacientů s celiakií, avšak u pacientů s NCG/PS byly nalezeny pouze ve 40-46 % [16,20], což je číslo velmi blízké jejich výskytu ve všeobecné populaci kavkazského původu (25-40 %) [33].…”

Human leukocyte antigen is better than serological screening for celiac diseases in rheumatological arthritis

“…About 0-12% of European population with CD showed lack of both these alleles (8). Approximately 25-40% of white normal Caucasians have HLA-DQ2/DQ8 haplotype while only 1-2% of the whole population would have CD (9,10). The frequency of different alleles is variable in different populations.…”