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. 2015 Apr;45(4):441-50.
doi: 10.1111/imj.12716.

Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective

J A Tye-Din  1 , D J S Cameron, A J Daveson, A S Day, P Dellsperger, C Hogan, E D Newnham, S J Shepherd, R H Steele, L Wienholt, M D Varney
Affiliations

Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective

J A Tye-Din et al. Intern Med J. 2015 Apr.

Abstract

The past decade has seen human leukocyte antigen (HLA) typing emerge as a remarkably popular test for the diagnostic work-up of coeliac disease with high patient acceptance. Although limited in its positive predictive value for coeliac disease, the strong disease association with specific HLA genes imparts exceptional negative predictive value to HLA typing, enabling a negative result to exclude coeliac disease confidently. In response to mounting evidence that the clinical use and interpretation of HLA typing often deviates from best practice, this article outlines an evidence-based approach to guide clinically appropriate use of HLA typing, and establishes a reporting template for pathology providers to improve communication of results.

Keywords: HLA typing; coeliac disease; diagnostics.

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Figures

Figure 1
Figure 1
Human leukocyte antigen (HLA) genotype and risk for coeliac disease (CD). HLA-DQ2.5, encoded by the DQA1*05 (α-chain) and DQB1*02 (β-chain) alleles, is associated with the highest risk for CD, especially when two copies of DQB1*02 allele are inherited (DQ2.5 homozygous). HLA-DQ8, encoded by DQA1*03 and DQB1*03:02, imparts moderate risk. The low risk HLA-DQ2 variant, HLA-DQ2.2, is encoded by the DQA1*02 and DQB1*02 alleles. HLA DQA1*05 without DQB1*02 (frequently observed as HLA-DQ7) appears to confer extremely low risk, but there is a paucity of data (not shown). APC, antigen presenting cell; X, any allele other than DQA1*05, DQB1*02 or DQB1*03:02.
Figure 2
Figure 2
Human leukocyte antigen (HLA) genotypes associated with coeliac disease (CD). 99.6% of 1008 patients with coeliac disease from Finland, France, Italy, Norway, Sweden and the UK expressed HLA-DQ2.5, a variant of HLA-DQ2.5 and/or HLA-DQ8. Similar proportions have been confirmed in Australia. This exceptionally strong HLA association imparts high negative predictive value for CD when these genotypes are absent. Notably, the high prevalence of these susceptibility genes in the general population (∼30–50%) renders HLA typing unhelpful as a stand-alone diagnostic for CD due to poor positive predictive value for CD. Green: HLA-DQ2.5 (A1:05, B1:02); Brown: HLA-DQ2.2 (B1:02+); Red: HLA-DQA1*05 (A1:05+); Yellow: HLA-DQ8 (DQA1:03, B1:03:02). HLA-DQ2.5 and variants are represented by green, brown and red. *Karell et al.
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