UK NEQAS and BSHI guideline: Laboratory testing and clinical interpretation of HLA genotyping results supporting the diagnosis of coeliac disease

Abstract

Coeliac disease is a common immune‐mediated inflammatory disorder caused by dietary gluten in genetically susceptible individuals. While the diagnosis of coeliac disease is based on serological and histological criteria, HLA‐DQ genotyping can be useful, especially in excluding the diagnosis in patients who do not carry the relevant DQ heterodimers: DQA1*05 DQB1*02, DQB1*03:02 or DQA1*02 DQB1*02 (commonly referred to as DQ2.5, DQ8 and DQ2.2, respectively). External quality assessment results for HLA genotyping in coeliac disease have revealed concerning errors in HLA genotyping, reporting and clinical interpretation. In response, these guidelines have been developed as an evidence‐based approach to guide laboratories undertaking HLA genotyping for coeliac disease and provide recommendations for reports to standardise and improve the communication of results.

HLA‐DQ7.5 and coeliac disease

“…Interpretation of HLA genotyping for CD can be challenging in clinical practice, and sometimes even misleading, and these proposed guidelines provide a valuable framework for standardizing HLA genotyping and its interpretation in the context of CD diagnosis. However, we would like to address a particular point of contention regarding excluding CD in patients expressing only HLA-DQA1*05 (in the form of DQ7.5) in the absence of HLA-DQ2.5, DQ8 and DQ2.2.The guideline suggests that the presence of DQA1*05 alone (which occurs in HLA-DQ7.5), without the corresponding DQB1*02 allele to form the DQ2.5 heterodimer in cis or trans, should lead to the exclusion of CD (Pritchard et al, 2023). However, in our experience, coeliac patients expressing only HLA-DQ7.5 do exist, and among coeliac patients diagnosed at our centre are roughly as common as those with only DQ8 or only DQ2.2.…”

“…The guideline suggests that the presence of DQA1*05 alone (which occurs in HLA-DQ7.5), without the corresponding DQB1*02 allele to form the DQ2.5 heterodimer in cis or trans, should lead to the exclusion of CD (Pritchard et al, 2023). However, in our experience, coeliac patients expressing only HLA-DQ7.5 do exist, and among coeliac patients diagnosed at our centre are roughly as common as those with only DQ8 or only DQ2.2.…”