Conventional wisdom and previous studies have indicated that negative testing for HLA-DQ8 and HLD-DQ2.5 alleles makes a diagnosis of celiac disease (CD), now or in the future, very unlikely. While ~60% of the population has one of these alleles, testing negative for these alleles has been regarded as having a high negative predictive value (>99%) and can be valuable in cases of equivocal diagnosis.
The authors of recent report (F Fernandez-Banares et al. Clin Gastroenterol Hepatol 2017; 15: 594-96) challenged this wisdom, noting that there is expected to geographical variation in the presence of these alleles. The goal of their study was to assess the prevalence of HLA-DQ2.5/8 among CD patients in Spain by reviewing previous studies; 12 studies were included. To be included, patients had to have villous atrophy, positive serology and available genotyping.
- Among 2963 Spanish CD patients, 3% “might be negative for HLA-DQ2.5/8.”
This is a brief report. It is expected that limitations would relate to the accuracy of genotyping and of excluding other causes of villous atrophy.
My take: (from the authors) “This information highlights the need to be cautious when ruling out CD only on the basis of genetics.”
Related blog posts:
- How slow do objective markers of CD decline with diet treatment
- Nuance in Celiac Disease Serology
- How Likely is Celiac Disease if My TTG Test Is Only a Little Bit Abnormal? | gutsandgrowth
- Will Asymptomatic Patients with “Potential” Celiac Disease Benefit from a Gluten-free Diet? | gutsandgrowth
L Kivela et al. J Pediatr 2017; 183: 115-21. This study divided children with CD into those identified via screening (n=145) and those identified due to clinical symptoms (n=359). Key findings:
- There were no differences in serology or histology between the two groups
- More than half (51.8%) of screen-detected patients had symptoms at diagnosis, but typically these were milder than in the clinically-detected group.
- Anemia was more common in the ‘clinical group’ 22.9% vs 7.1% (screen group) as was poor growth (36.9% vs. 15.7%).
AJ Irvine et al. Am J Gastroenterol 2017; 112: 65-76. (Thanks to Ben Gold for this reference) In this systemic review with 15,256 individuals (& 9,275 with irritable bowel), “prevalence of positive celiac serology and biopsy-proven CD was significantly higher in subjects with symptoms suggestive of IBS vs. healthy controls.” The odds ratio for serology-positive and/or biopsy-proven CD ranged from 2.75 to 4.48, though there was no significant increase in these ORs for North American studies.