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) is well known. This genetic factor is necessary – but not sufficient – to develop CD. Basically, almost 100% of CD patients are carriers of the aforementioned HLA-DQ background and several studies emphasized the main role of the HLA-DQB1*02 allele in such a genetic predisposition.
CD is underdiagnosed in both developing and developed countries, due to several aspects: Indeed, many 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 is still debated and this study might provide some additional insights, in order to find novel screening strategies.
Our aim was to define and assess the carrier frequency of the specific allelic variant HLA-DQB1*02 (coding the β chain of DQ2 heterodimer) in the population of patients diagnosed with CD.
In order to achieve our aim, we performed a systematic review, according to the PRISMA guidelines, by retrieving all original articles (case series, case–control, cross-sectional, and retrospective cohort studies) describing CD patients’ HLA-DQB1 genotype in detail. Any original articles, in which CD patients’ HLA-DQB1 genotype was described in such a way and detail that the number of HLA-DQB1*02 carriers could be clearly defined (within the total of the respective CD population), were considered.
As a result of our literature search, 38 studies were finally included in the present systematic review, since those provided details of the HLA-DQB1 genotype in such a way that could allow to assess the HLA-DQB1*02 carrier frequency among CD patients. Among 4945 HLA-DQ genotyped CD patients, the HLA-DQB1*02 carrier frequency resulted to be 94.94%, meaning that only 5.06% of CD population was completely lacking this allelic variant. If only the CD pediatric population is considered, similar figures are obtained: Only 5.31% is lacking a copy of this allelic variant. Finally, if we consider only the studies whereby the prevalence of CD patients also affected with type 1 diabetes mellitus (DM1) was supposed or clearly established to be very low, the frequency of non-HLA-DQB1*02 carriers among CD patients dropped up to 3.65%.
According to the findings of this systematic review, < 4%-5% of CD-predisposed children may be lost through a preliminary evaluation of the presence/absence of HLA-DQB1*02 allele, regardless of the presence of other HLA-DQB1 and HLA-DQA1 CD-predisposing alleles.
A cost-effective and widened screening approach may be very helpful in both developed and developing countries, if a sustainable strategy could be implemented through a low-cost targeted genetic test for the HLA-DQB1*02 allelic presence, along with appropriate algorithms for serological screening in individuals resulting to be genetically predisposed to CD.