Genotyping strategy could boost celiac screening efficacy

Dec 24 2013

By Joanna Lyford, Senior medwireNews Reporter

Genotyping for human leukocyte antigen (HLA) followed by biopsy is a sensitive strategy for detecting histopathologic lesions in the close relatives of people with celiac disease (CD), research indicates.

Around half of individuals screened with this approach would be expected to show some form of enteropathy, report Santiago Vivas (University Hospital of León, Spain) and co-workers in the European Journal of Gastroenterology and Hepatology.

The first-degree relatives of people with CD are at increased risk for the disorder but classic serologic markers of CD have a low sensitivity in adults; indeed, affected relatives may have negative serology despite lymphocytic enteritis and symptoms of malabsorption.

In this study, Vivas et al evaluated a screening strategy of HLA-DQ2/8 genotyping followed by duodenal biopsy among 67 first-degree relatives (mean age 34 years) of CD patients.

At baseline, 54% had gastrointestinal symptoms, with dyspepsia and diarrhea being most prevalent. One-third were homozygous or heterozygous for either the HLA-DQ2 or HLA-DQ8 genotype and 25% tested positive for tissue transglutaminase antibodies (tTGAs).

Histopathology was abnormal in 48% of all participants; specific alterations included villous atrophy (Marsh III) – the hallmark of CD – in 28.3% and inflammation (Marsh I/II) in 19.4%.

Among the 17 participants who tested positive for tTGA, 16 had Marsh III histopathology and one had Marsh I; meanwhile, among the 50 participants with negative tTGA serology, three (6%) had villous atrophy.

The severity of histopathology was negatively correlated with age, note Vivas et al, such that participants with normal biopsy results were significantly older than those with lymphocytic enteritis and mucosal atrophy.

Interestingly, there was no correlation between the presence of symptoms, anemia, or autoimmune disease with the presence of degree of duodenal damage found on biopsy.

However, people who were homozygous for the HLA-DQ2 and DQ8 alleles were more likely to test positive for tTGA (32 vs 12%) and to have duodenal atrophy (29 vs 19%) than were heterozygotes.

Noting that this approach was more than three-fold more sensitive than serology-based screening, the authors conclude: “[A] diagnostic strategy on the basis of HLA-DQ genotyping, followed by a duodenal biopsy in positive relatives, may be an alternative to detect [first-degree relatives] with alterations in the duodenal mucosa irrespective of the serological test results.”

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