StandardiSed molecular genetic microarrayS for laboratory diagnoSticS


By: Dr Jacqueline Gosink, Product Manager, EUROIMMUN AG, Luebeck, Germany


INTRODUCTION Molecular genetic analysis is gaining new momentum in diagnostics as the genetic components behind many diseases become better characterised. Human leukocyte antigen (HLA) alleles, for example, exhibit extreme genetic polymorphism. Specific alleles are associated with particular autoimmune and inflammatory diseases, for example coeliac disease, psoriasis and ankylosing spondylitis, and HLA determination is now an important tool for both diagnosis and prediction of disease risk. Other well- characterised mutations, such as those in the blood coagulation factors V and II, are analysed in the management of conditions such as thrombophilia. The following examples illustrate how genetic parameters are now an integral part of routine diagnostics.


HLA-DQ2 AND DQ8 IN COELIAC DISEASE Coeliac disease (CD) is an immune-mediated systemic disorder triggered in genetically predisposed individuals by gluten and related prolamins. It can present in many forms, including classic, silent, latent or potential variants. In addition to gastrointestinal symptoms, its manifestations include osteoporosis, neuropathies, carditis, pregnancy problems, lymphoma and Duhring’s dermatitis herpetiformis. The only effective treatment is observance of a gluten-free diet.


028 MEDLAB MAGAZINE ISSUE 1 2012 The principle determinants of genetic susceptibility for CD are


the HLA alleles DQ2 and DQ8, which are found in near to 100% of sufferers. Around 95% exhibit the DQ2 genotype, while the remainder have the DQ8 genotype. However, the presence of HLA-DQ2/DQ8 is not sufficient by itself to cause coeliac disease. Around a third of the healthy population exhibits DQ2/DQ8 alleles. Thus, the value of HLA- DQ2/DQ8 analysis lies predominantly in exclusion diagnostics. The role of HLA-DQ2/DQ8 in coeliac disease diagnostics


has gained pivotal significance with the recent publication of new guidelines from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). HLA-DQ2/DQ8 analysis is now recommended as the first-line test for screening asymptomatic persons who have a high risk of developing CD, for example relatives of CD patients or persons with associated conditions such a type 1 diabetes mellitus, Down’s syndrome, autoimmune thyroid or liver disease, Turner’s syndrome, Williams’ syndrome or selective IgA deficiency. If HLA-DQ2/DQ8 is negative, the risk of CD is negligible and no further follow up is necessary. Determination of HLA-DQ2/DQ8 is also recommended by


ESPGHAN as a confirmatory test in the diagnosis of CD in symptomatic persons. It is one of a triad of laboratory parameters, along with anti-tissue


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