Impact on parents of HLA-DQ2/DQ8 genotyping in healthy children from coeliac families

Abstract

on behalf of the PreventCD study groupDue to the association of coeliac disease and HLA-specificities DQ2 and DQ8, HLA-typing can be used for risk determination of the disease. This study was designed to evaluate the knowledge of parents from coeliac families regarding HLA-typing and the impact of HLA-typing on the perception of the health of their children. A structured questionnaire was sent to the Dutch, Spanish and German parents participating with their child in the European PreventCD study on disease prevention in high-risk families, addressing parents' understanding of and attitude towards HLA-typing, distress related to HLA-typing and perceived health and health-related quality of life of their children. Sixty-eight percent of parents of 515 children returned the questionnaires, with 85% of children being DQ2/DQ8 positive. The majority of all parents answered the questions on knowledge correctly. Forty-eight percent of parents of DQ2/DQ8-negative children thought their child could develop coeliac disease. More distress was reported by parents of DQ2/DQ8-positive children (Po0.001). All parents showed few regrets and would repeat HLA-typing in future children. Perceived health and health-related quality of life were similar. In conclusion, we can say that misinterpretation of DQ2/DQ8-negative results by parents is frequent. DQ2/DQ8-positive results do not affect perceived health and health-related quality of life of children but may cause temporary negative feelings among parents. Parents of coeliac families seem to support HLA-typing. INTRODUCTIONCoeliac disease (CD) is the most common intolerance to a dietary component in children and adults. 1 In genetically predisposed individuals, CD is precipitated by the ingestion of gluten, which are storage proteins in wheat (gliadin), rye (secalin) and barley (hordein). 1,2 T-cells in the lamina propria of the small intestines recognize the gluten peptides when they are bound to the human leukocyte antigen (HLA) class II specificities DQ2 and/or DQ8 on antigen-presenting cells. 2 Screening for CD can be done by measuring CD-specific antibodies against the enzyme tissue transglutaminase type 2, endomysium and deamidated gliadin peptides. 3 CD is treated with a gluten-free diet. Long-term complications of untreated CD are among others diarrhoea, abdominal pain, perinatal problems, osteoporosis and cancer. 1,4 CD has a strong genetic component, as 90% of CD patients carry the class II HLA-DQ2 haplotype, about 5% the HLA-DQ8 molecule [5][6][7][8] and the rest usually the half of the HLA-DQ2 heterodimer.The HLA-DQ2 and DQ8 haplotypes are present in over 25% of the general population, 6 but only 1% actually develops CD. 1 This indicates that HLA-DQ2 and -DQ8 haplotypes are necessary but not sufficient for disease development. Around 40% of the heritability of CD is explained by HLA-DQ2 and/or -DQ8. First-degree family members of CD patients who are HLA-DQ2 and/or DQ8 positive (DQ þ ) have an increased risk of approximately 10% to develop CD. 9

Repeated Screening Can Be Restricted to At‐Genetic‐Risk Birth Cohorts

“…Policy documents of genetic screening of children state that the testing should be driven by the best interest of the child (25). Then again, study participants in screening based on HLA-DQ genotyping are generally receptive to continuing participation despite the knowledge of their increased risk for CD (26). One should bear in mind that 40% of the disease risk can be explained by genetics (27); the remainder is probably triggered by the environment (9).…”

Coeliac disease and gluten-related disorders in childhood

“…Parents of affected children support HLA-typing of their other children to assess the risk of the disease. 48 …”

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

“…HLA-DQ2/DQ8 has a prevalence of 90-100% amongst children diagnosed with CD and in up to 85% of firstdegree relatives. [6][7][8][9] It is positive in 25-30% of proven non-coeliac cases, 93% of non-coeliac individuals with diabetes mellitus and 75-80% of non-coeliac firstdegree relatives of CD patients. 8,9 Around 25-40% of the European population is positive for HLA-DQ2/DQ8, but only 2-3% of these will develop CD.…”

“…[6][7][8][9] It is positive in 25-30% of proven non-coeliac cases, 93% of non-coeliac individuals with diabetes mellitus and 75-80% of non-coeliac firstdegree relatives of CD patients. 8,9 Around 25-40% of the European population is positive for HLA-DQ2/DQ8, but only 2-3% of these will develop CD. 1 Therefore, this expensive test (HLA-DQ2/DQ8 costs £21-£100, while cost for tTG is £6 only) should not be used to screen children for CD.…”

“…6–9 It is positive in 25–30% of proven non-coeliac cases, 93% of non-coeliac individuals with diabetes mellitus and 75–80% of non-coeliac first-degree relatives of CD patients. 8,9…”