Published online Mar 28, 2020. doi: 10.3748/wjg.v26.i12.1365
Peer-review started: December 19, 2019
First decision: January 12, 2020
Revised: March 10, 2020
Accepted: March 22, 2020
Article in press: March 22, 2020
Published online: March 28, 2020
Celiac Disease (CD) is an immune-mediated disorder, in which the HLA immunogenetic background (DQ2 and DQ8 heterodimers) and environmental trigger (gluten) are well established. Indeed, both factors are necessary – but not sufficient – to develop CD. However, it is very likely that CD is underdiagnosed in both developing and developed countries, due to several aspects, including the fact that a lot of patients present mild and/or atypical symptoms, without the presence of any recognized risk factors. Therefore, the possibility and feasibility of widened screening strategies to identify CD patients are debated.
To provide further evidence of the main epidemiological importance of HLA-DQB1*02 allele in the population of CD patients.
We performed a systematic search in PubMed, EMBASE, Cochrane, Web of Science and Scopus databases, in order to produce a systematic review assessing the carrier frequency of HLA-DQB1*02 allele in the celiac population. Following the PRISMA guidelines, we retrieved all the original articles describing CD patients’ HLA-DQB1 genotype in such a way that could allow to assess the HLA-DQB1*02 carrier frequency among CD patients, along with the evidence of the appropriate diagnostic work-up to achieve a correct and final diagnosis of CD.
The final output of this systematic search in the medical literature consisted of 38 studies providing the appropriate HLA-DQB1 genotype information of the respective CD population. According to this systematic review, including a pool of 4945 HLA-DQ genotyped CD patients, the HLA-DQB1*02 carrier frequency was 94.94%, meaning that only 5.06% of CD patients were completely lacking this allelic variant. Interestingly, if we consider only the studies whereby the prevalence of CD patients affected with type 1 diabetes mellitus was supposed or clearly established to be very low, the frequency of non-HLA-DQB1*02 carriers among CD patients dropped to 3.65%.
Such a high carrier frequency of the HLA-DQB1*02 allelic variant (which is > 95%-96% in CD patients without risk factors, like type 1 diabetes mellitus comorbidity) might be exploited to consider a cost-effective and widened screening approach. If a sustainable strategy could be implemented through a low-cost targeted genetic test to detect the individual presence of HLA-DQB1*02 allele, an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD, might be considered.
Core tip: It is well known that HLA-DQ genotyping is useful to assess the individual susceptibility to Celiac Disease (CD) with very high - if not absolute – discriminatory power. Indeed, it is very unlikely that individuals who do not carry specific HLA-DQ alleles coding MHC-DQ2 and MHC-DQ8 heterodimers, may develop CD. Here, we aim at providing further evidence of the specific epidemiological importance of HLA-DQB1*02 allele in the population of CD patients. Briefly, based on 38 original articles that we included in this systematic review (which provided a pool of 4945 HLA-DQ genotyped CD patients, overall), we could find a very high carrier frequency of the HLA-DQB1*02 allelic variant. Indeed, > 95%-96% of CD patients resulted to carry at least one copy of the HLA-DQB1*02 allele. This knowledge might be exploited to consider a cost-effective and widened screening approach: If a sustainable strategy could be implemented through a low-cost targeted genetic test for CD, an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD, might be considered.