Abstract
Magnitude of gluten-specific T-cell responses in coeliac disease (CD) might be dependent on HLA-DQ2 gene dose. We aimed to investigate the effects of HLA-DQB1*02 allele dose on clinical outcomes. We reviewed the charts of all coeliac patients attending to three Hungarian university clinics after 1997 and included those patients, who (a) were diagnosed with CD, (b) underwent high-resolution HLA typing and (c) were ≥18years at the time of data collection. HLA typing was performed to determine DQB1*02 allele dose. Patients were divided into risk groups by DQB1*02 allele dose, as follows: high-, intermediate- and low-risk groups corresponded to a double, single and zero doses, respectively. We used ANOVA and Pearson's chi-squared test to explore association between HLA risk and clinical variables. A total of 727 coeliac patients attended the clinics but only 105 (14.4%) patients were eligible for inclusion. High, intermediate and low HLA risk patients comprised 35.3%, 52.3% and 12.3% of the study population, respectively. Double dose of HLA-DQB1*02 was more frequent in patient with high tTGA level (>10 times the upper limit of normal; p=0.045). Gene dose was not associated with younger age at diagnosis (p=0.549), gender (p=0.739), more severe diagnostic histology (p=0.318), more frequent classical presentation (p=0.846), anaemia (p=0.611), metabolic bone disease (p=0.374), dermatitis herpetiformis (p=0.381) and autoimmune diseases (p=0.837). Our study shows a significant gene dose effect in terms of tTGA level at diagnosis, but no significant association between HLA-DQB1*02 allele dose and the clinical outcomes in CD.
Highlights
Coeliac disease (CD) is a highly heritable, immune‐mediated systemic disorder
We aimed to investigate the association between HLA‐DQB1*02
The theoretical background suggests a significant gene dose effect in coeliac disease (CD), we proved only association between HLA‐DQ2 gene dose and tTGA level but not in connection with the clinical features
Summary
The consumption of gluten‐containing cereals triggers a T‐cell‐mediated immune cascade resulting in impairment of small intestinal villous architecture and systemic manifestations. Sequelae include severe tissue destruction accompanied by remodelling of small intestinal villous architecture (Kupfer & Jabri, 2012; Tjon, Van Bergen, & Koning, 2010). Unlike heterozygotes, who have multiple potential allele combinations, only some of them can present gliadin peptides (van Belzen et al, 2004). DQ2.5 homozygotes have a fivefold risk of CD, as compared to heterozygotes (Abraham & Inouye, 2015; Koning, 2012; Pietzak, Schofield, McGinniss, & Nakamura, 2009; Vader et al, 2003; van Belzen et al, 2004). | 75 allele dose with clinical parameters thereby attempting to define the role of HLA status in clinical risk stratification of CD patients
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