Pediatric Celiac Disease in Kazakhstan: epidemiological analysis and implementation of screening and diagnostic strategies.

Faculty Development Competitive Research Grants 2020-2022

Celiac Disease (CD) is an autoimmune disorder occurring in genetically predisposed individuals who develop an adaptive immune response to gluten, in particular, to gliadin and its related peptides contained in wheat and other cereals. Therefore, once diagnosed, the curative therapy consists of gluten-free diet (GFD).
The prevalence of CD in the general pediatric population is estimated to be around or at least 1%, with some geographical and ethnic variations. Therefore, in the general population, CD results to be the most frequent autoimmune non-communicable disease after thyroid autoimmune diseases, if considered overall, but it is by far the most common diagnosis of autoimmunity in children.
Among non-communicable and autoimmune diseases (NCDs), CD presents some peculiar aspects in term of etiology or, at least, as regards the available knowledge of it: the necessary environmental trigger (namely, gluten dietary exposure) and the HLA predisposing genetic background (DQA1*0501-DQB1*02 and DQA1*0301-DQB1*0302, coding class II MHC heterodimers DQ2 and DQ8, respectively) are well known. Globally, these HLA predisposed individuals account for 30-40% of the general population, but only a small portion of them will develop CD over the life, despite the comparable exposure to gluten foods. However, despite the high prevalence reported above, CD is likely to be under-diagnosed, even in developed countries, where all the diagnostic resources are available and more disposable for most part of the population. Indeed, according to the so-called “celiac iceberg” epidemiological model, only a minority of cases (the emerged tip of the iceberg) are clinically well-evident and timely diagnosed, whereas most part of cases (the iceberg mass under the water surface) are under-diagnosed (and, then, cannot receive the curative gluten-free diet) or are diagnosed with delay and thanks to screening procedures because of other co-morbidity or family risk (see later). Importantly, a lot of CD cases do not manifest with typical malabsorption-related gastrointestinal (GI) symptoms, which may be actually completely absent. Moreover, CD is very likely to be even more under-diagnosed in developing countries, because of the major attention to infectious diseases and because of the poor awareness of CD in term of prevalence and clinical expression, as it is in Kazakhstan, unfortunately.
Children represent a particularly vulnerable population with respect of this disease. Indeed, a missed or delayed CD diagnosis can affect children’s health much more negatively than adults, as permanent and lifetime negative outcomes may result.
In Kazakhstan, the epidemiological burden of CD is unknown, as specific clinical studies are completely lacking. Indeed, no study investigating CD in Kazakhstan is currently present in the international peer-reviewed medical literature.
Therefore, the general aim of this Project is to provide an epidemiological overview on pediatric CD and, importantly, to draft a cost-effective and feasible diagnostic and screening strategy for Kazakhstan and similar countries, characterized with the same social, demographic and economic context. Concomitantly, this Project will also provide genetic HLA-DQ data, which will be useful in the worldwide open debate on early diagnosis and widened screening for CD in children.
Therefore, this Project pursues multiple specific research objectives, as follows:
I)Defining the epidemiological burden of celiac disease (CD) in the pediatric population of Kazakhstan (which is very likely to be much greater than expected);
II)Providing the most appropriate and effective diagnostic screening, according to the epidemiological, geographical, financial and social background in Kazakhstan, in order to treat CD appropriately and prevent long-term complications;
III)Providing clinical, laboratory and genetics data about the risk of CD in first-degree relatives (FDRs) of pediatric index cases, in order to contribute to the open debate and research pursuing the optimal widened screening strategy for pediatric CD.