Integration of Genetic and Immunological Insights into a Model of Celiac Disease Pathogenesis

The many faces of celiac disease: Clinical presentation of celiac disease in the adult population

XVIII Latin American Congress

Role of tissue transglutaminase in celiac disease.

Celiac disease (CD) presents with a spectrum of clinical disorders, mainly of autoimmune mechanism (1). A wide variety of liver injuries, particularly of the inflammatory type, have been reported in patients with CD (2). More rarely, other liver lesions, such as hepatic steatosis (3), which may be severe (4), cirrhosis and hepatocellular carcinoma, are found in the liver biopsies of children and adults with CD at the time of diagnosis (5). Among the inflammatory lesions, both mild liver injuries with limited fibrosis as well as severe and progressive liver diseases have been described (6). The first report of liver involvement in CD appeared in 1977. In this group of 74 newly diagnosed adults with CD, 40% had an elevation of serum aminotransferase activity, which normalized in most cases, during treatment with gluten-free diet. In addition, of 13 patients, 5 showed signs of reactive hepatitis and 7 (16%) showed histologic lesions of different types and severity ranging from steatosis with focal fibrosis to pronounced fibrosis and cirrhosis (7). Approximately 10 years later, in a study of children younger than 2 years of age with newly diagnosed CD and gastrointestinal symptoms, mild to moderate elevation of serum aminotransferase activity was observed in approximately two thirds of cases (8). The biochemical abnormalities, which usually resolved on a gluten-free diet, were associated with a histologic picture of mild mononuclear infiltrate of the portal tract with non-aspecific signs of liver cell damage and Kupffer cell hyperplasia (9). CD may present atypically as a cryptogenic liver disorder. The first description of this type of onset appeared in The Journal of Pediatric Gastroenterology and Nutrition in 1986 in a case report of a young girl with a persistent and cryptogenic elevation of serum aminotransferase and whose liver biopsy showed mild inflammation of the portal tract (10). The diagnosis of CD was suggested by a high titre of antireticulin antibody and was later confirmed by jejunal biopsy. A series of six children with persistent elevation of aminotransferase activity and with a histopathologic picture ranging from reactive hepatitis to moderately active chronic hepatitis was reported subsequently. These children were asymptomatic and jejunal histology typical of CD. In all children, aminotransferase activity normalized on a gluten-free diet. Normalization of histologic lesions was documented in two children, and in three others, a challenge with gluten was followed by an increase of serum aminotransferases (11). More reports in children and two retrospective studies in adults confirmed these observations (12–14) and suggested that as many as 9% of patients with persistent and cryptogenetic elevation of serum aminotransferases may be affected by asymptomatic CD (15). This condition, was once called gluten hepatitis (16). We now suggest defining the condition as celiac hepatitis, characterized by: Absence of hepatomegaly, splenomegaly, or both and of any clinical features suggesting chronic liver disease; Absence of hypergammaglobulinemia and of serum autoantibodies (excepted for antitransglutaminase-related autoantibodies); and Presence of mild lobular and portal tract inflammation, reversible on a gluten-free diet. A high prevalence of CD (4.3%), four to ten times higher than the expected, was recently found in Finland in a group of 185 adult patients who had undergone liver transplantation (17). The nature of the severe, end-stage liver disease leading to liver transplantation was, in most cases, autoimmune. The finding that the prevalence of CD is higher in adult patients with an autoimmune liver disease than in the general population was first reported by Lindberg et al. in 1979 (18). In this study, while systematically searching for CD in 16 adults with chronic hepatitis B surface antigen-negative active hepatitis, Lindberg et al. found three patients with CD, two of whom had no gastrointestinal symptoms. A recent study by Volta et al. (19) confirmed this observation, demonstrating a 4% prevalence of CD in a population of 181 patients with autoimmune hepatitis. A high prevalence of CD was reported recently in adults with autoimmune diseases of the bile ducts such as primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis (20). Particularly strong evidence supports the association between primary biliary cirrhosis, an autoimmune liver disorder peculiar to adulthood, and CD. Prevalence of primary biliary cirrhosis has been reported to be as high as 3% in celiac patients, and about 6% of individuals with CD may be affected by primary biliary cirrhosis (21). A Scandinavian study has confirmed these data, finding a 20 fold increase in the prevalence of primary biliary cirrhosis in adults with CD (22). These studies suggest an active crosschecking of CD, by serum anti-transglutaminase antibodies, in patients with autoimmune diseases of bile ducts. In children, sporadic cases of autoimmune hepatitis or autoimmune sclerosing cholangitis associated with CD have been reported (16,23). In a multicenter study in Italy, autoimmune hepatitis occurred in 1.1% of 909 children with CD and in none of the healthy controls or a control group with Crohn disease (24) In another study of 96 children with autoimmune hepatitis at King's College, London, the prevalence of CD was found to be significantly higher (3.4%) than expected (25). In the patients with CD, the autoimmune hepatitis had the serologic characteristics of type 1, which is associated with anti–smooth-muscle autoantibodies with anti-actin specificity (26). The features of the autoimmune liver disorders associated with CD were studied recently in a multicenter survey by the Italian Society of Pediatric Gastroenterology and Hepatology, which collected data on 14 patients with CD and an autoimmune liver disease (27). In most cases, the diagnosis of autoimmune liver disease preceded the diagnosis of CD, although in retrospect, some evidence of liver damage had been present in most patients since the onset. In some patients, however, an acute icteric hepatitis developed a few months after the diagnosis of CD and the start of a gluten-free diet. When an autoimmune liver disease developed in the setting of silent CD, the diagnosis of CD was suggested by sideropenic anemia or by systematic autoantibody screening. This study suggests that: All types of autoimmune liver disorder may be associated with CD, with autoimmune hepatitis the disorder most frequently found; All subtypes of autoimmune hepatitis can be associated with CD: type 1, as previously suggested (25), type 2 characterized by autoantibodies against liver or kidney microsomes (28), liver cytosol (29), or both, and even seronegative autoimmune hepatitis (30); Complete immunoglobulin A deficiency and the presence of an eosinophilic infiltrate of the portal tracts are a characteristic of patients with autoimmune liver disease and CD; and Reintroduction of gluten into the diet may be associated with a relapse in patients free from immunosuppression. The mechanism of liver injury in celiac patients is poorly understood. The two types of liver injury described may represent a spectrum of a single disorder where individual factors, such as precocity and duration of exposure to gluten, may influence the reversibility of liver damage (2–24). Autoimmune liver disorders and CD share common HLA class II aplotypes. In the white adult population, two aplotypes have been identified as susceptibility markers of autoimmune hepatitis: the complex HLA A1 B8 DR3 and the aplotype HLA DR4. (31). Similarly, specific HLA class II antigens such as HLA-DR3, particularly the HLA-DQ2 molecule and HLA DR4, confer susceptibility to CD (32). Patients with CD have an increased intestinal permeability to different substances that, absorbed in larger amounts through the damaged intestinal mucosa, may have a direct toxic effect on the liver. Alternatively, it may initiate an immunologic reaction toward liver antigens. An increased prevalence of organ-specific and non–organ-specific autoantibodies such as antithyroid or antipancreatic islet cell has been described in CD patients on a gluten-containing diet. These autoantibodies appear to be gluten dependent, because in most cases, they become undetectable on a gluten-free diet (33). So, increased permeability to intraluminal gut antigens could induce, in genetically predisposed individuals, an immune response both against antigens sharing common epitopes to self-liver-proteins and against usually cryptic antigens that are unmasked by the reaction with gliadin. It is known that mucosal damage in CD leads to exposure of tissue transglutaminase enzyme, the target antigen recognized by anti-endomysial antibody (34). The hypothesis that this autoantibody plays a role in extraintestinal manifestations of CD and particularly in liver injury is supported by the recent finding of extracellular deposition of immunoglobulin A class anti-tissue transglutaminase in liver biopsy of two patients with active CD (35). In conclusion, liver involvement in individuals with CD comprises: A so-called celiac hepatitis, which develops both in patients with intestinal symptoms and in individuals with asymptomatic CD. This condition is frequent, benign, clinically silent, possibly immune mediated, and resolves on a gluten-free diet. An autoimmune liver disease, which is usually an autoimmune hepatitis. These disorders are rare and in most cases are associated with clinical signs and symptoms of chronic liver disease. Moreover, they do not recover simply with the administration of a gluten-free diet, but need specific immunosuppressive therapy. A fortuitous association between CD and liver cannot be excluded because of the high prevalence of CD in the general population. These considerations recommend a rigorous search for evidence of liver disease among patients with newly diagnosed CD by monitoring aminotransferases activity. Likewise a search for CD should be initiated by obtaining anti-transglutaminase autoantibodies in children with any inflammatory liver disease of unknown cause. Attention should be paid in patients with chronic liver disease, to the risk of false-positive results of anti-transglutaminase assay because of the frequent contamination of guinea pig transglutaminase by hepatic proteins. The use of anti-human transglutaminase usually avoids this risk (36,37).

Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNFalpha gene polymorphism (-308) associated with susceptibility to several autoimmune diseases was studied. Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNFalpha study. HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%). Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.

Celiac Disease Beyond the Gut

The high prevalence of celiac disease in patients with autoimmune hypothyroidism, compared to the general population, has been well documented but screening for celiac disease is not recommended as yet in otherwise asymptomatic hypothyroid patients. In recent years the high prevalence of undiagnosed celiac disease in the general population, largely as a result of the many atypical manifestations of the disease, has become apparent. We report the case of a 58-year-old woman with autoimmune hypothyroidism who was initially suspected of having celiac disease on the basis of apparent resistance to levothyroxine therapy, and who had no other clinical or laboratory clues to suggest the diagnosis. Cases of undiagnosed celiac disease causing levothyroxine malabsorbtion have previously been described, but all previous cases had other obvious manifestations of the disease. We believe that this atypical presentation of celiac disease warrants further attention, and that the diagnosis of celiac disease should always be considered in patients requiring higher than expected doses of thyroid hormone replacement, even in patients with normal bowel habit, and no other apparent manifestations of the disease.

Background: The relatively common co-occurrence of type 1 diabetes (T1D) and celiac disease (CD) suggests these disorders share common pathogenic etiologies. Summary: T1D and CD are strongly linked to closely related high-risk human lymphocyte antigens (HLA-DR-DQ). High-risk HLA molecules bind specific fragments of gluten or the islet self-antigen(s) and present these antigens to antigen-responsive T cells. In an appropriate proinflammatory environment, the autoimmune response results in destruction of the intestinal enterocyte and/or the pancreatic beta cell. Environmental factors have been implicated in the etiology of T1D and CD because (1) identical twins are only partially concordant for these disorders and (2) incidence rates of T1D and CD have been steadily rising for decades. Prospective studies in infants genetically predisposed to T1D and CD showed that antibody positivity to both disorders begins in the first 1–3 years of life. Viral infections and early exposure to gluten or cow’s milk in the infant diet have been implicated in disease pathogenesis. However, delaying introduction of gluten in the infant diet until 12 months of age had no impact on the development of islet or celiac autoimmunity. Weaning nursing infants to hydrolyzed infant formula had no impact on the development of T1D. Viral infections have been suspected of playing a role in T1D pathogenesis for decades. A large international prospective study (TEDDY) has shown increased risk of T1D autoimmunity particularly when >5 respiratory infections or febrile infections have occurred in the 9 months preceding the appearance of islet antibodies. Provocative data in animal models of T1D suggest the microbiome may play an important role in the pathogenesis of T1D. Breastfeeding, diet, infections, antibiotics, and method of birth alter the composition of the microbiome. Human data indicate subtle differences in the microbiome of children with T1D autoimmunity, while intestinal dysbiosis has been clearly demonstrated in CD. Alterations of the integrity of the intestinal mucosa plays an important role in the pathogenesis of CD, and the NOD mouse model suggests an important role of a leaky intestinal epithelium in T1D as well. Key Message: Immunogenetics and the environment are closely interrelated in the pathogenesis of T1D and CD. Large well-designed prospective studies in at-risk populations informed by scientifically rigorous studies in animal models are likely to have the greatest impact on our understanding of the complex pathogenesis of these detrimental autoimmune disorders.

Background: In the last few years the prevalence of celiac disease (CD) seems to have increased. It is clear that subclinical and silent CD exist in a large subgroup of the celiac population. Methods: The aim of this study was to evaluate the prevalence of CD in an apparently healthy population. Blood samples were obtained from 1000 apparently healthy blood donors at Arnhem and Nijmegen Blood Donation Centers from January 1997 through April 1998. Sera from 660 blood donors were assayed for total IgA. By means of immunofluorescence, antibodies, including those to endomysium (EMA), were determined. Serum immunoglobulin levels (IgA) were assayed by means of nephelometry. All donors who had positive serology for EMA underwent small-intestinal biopsy. Results

Vaccination is an efficient and reliable means of protection against common hepatitis B virus (HBV) infections [1]. Between 90% and 95% of the adult population responds to HBV vaccination [2][3], and 4-10 % of vaccine recipients fail to respond to standard immunization [1][4][5]. The ability to respond to recombinant HBV vaccine is associated with immunogenetically condition because of multiple candidate genes [6][7]. Some specific HLA haplotypes are considered to be the most important genetic markers for non-responders, who are found to carry specific haplotypes such as B8, DR3, and DQ2 [6][7]. Since HLA genotypes play an important role in unresponsiveness to the HBV vaccine, celiac disease (CD) may be associated with this unresponsiveness [8]. CD is a common autoimmune disorder, which has a particularly strong association with the presence of HLA-DQ2 in 90-95% of the patients [9][10][11][12]. In an issue of Hepatitis Monthly [13], Ertekin et al. reported the results of their study on 52 children with CD and 20 age- and sex-matched healthy children who received HBV vaccination as per an immunization schedule. The proportion of children in the CD group who failed to respond to HBV vaccination (32 of 52) was significantly higher than the proportion of control individuals who did not (18 of 20; 61.5% vs. 90%; P < 0.05). Ertekin et al. concluded that unresponsiveness to hepatitis B vaccination was found in a higher percentage in children with CD than the control group. They concluded that response to the HBV vaccine in children with CD should be investigated and a different immunization schedule should be developed for them. They also suggested that compliance with a gluten-free diet may improve the immune response of celiac children to the HBV vaccine. Most studies on this topic have demonstrated that the number of children with CD who failed to respond to the HBV vaccine is significantly greater than that of healthy children [4][5][8][14]. In a similar study on an adult cohort, Noh et al. found that of 23 adults with CD who had completed a full course of HBV vaccination, 19 tested positive for HBsAb and 13 did not show long-term immunity [15]. This association of HLA with non-responsiveness to HBV vaccination was further confirmed in a study by Stachowski et al., where 34 out of 153 patients with end-stage renal disease were non-responsive to a recombinant HBV vaccine and HLA-DQ2 was found almost exclusively in the non-responder group [7]. Longer intervals between vaccination and antibody testing might be one of the reasons for significantly low protective post-vaccination HBV antibody titers even in CD patients who comply with dietary guidelines [8][14]. Therefore, revaccination is recommended when the patients are following a controlled gluten-free diet. This study was not designed to determine the presence of HLA-DQ2 and HLA-DQ8 in both the groups. Therefore, future studies evaluating the HLA haplotypes in CD and control groups should aim to characterize the role of HLA typing in the response to HBV vaccination. As in the case of other conditions and as indicated by the strong evidence for the protective role of GFD, early diagnosis of CD may obviously increase the percentage of patients responding to the HBV vaccine. Moreover, beginning with a short duration, strict, gluten-free diet seems to play a positive role in the development of antibody memory. Given the high prevalence of CD in the general population and a lack of response to HBV vaccine in untreated patients, we think that non-responsiveness to HBV vaccine necessitates routine assessment in patients with CD. Non-responsiveness to HBV vaccine may be a possible sign of undiagnosed CD or may suggest noncompliance with gluten-free diet.

Adult Celiac Disease: Report of a Case

Introduction. The group of gluten-dependent diseases currently comprises 3 pathological conditions: celiac disease, non-celiac gluten intolerance and wheat allergy. Celiac disease is a chronic, immune-inflammatory disease that occurs in genetically predisposed individuals in response to exposure to the main cereal protein - gluten. It is characterised by damage to the small intestinal mucosa, leading to its atrophy with corresponding intestinal and extraintestinal clinical manifestations. The treatment is a lifelong gluten-free diet. Gluten intolerance is a condition characterised by the onset of irritable bowel syndrome-like symptoms within hours or days of eating gluten-containing foods. These symptoms disappear quickly when the consumption of gluten-containing products is stopped. The causes of gluten intolerance are amylase inhibitors, trypsin and fructans (FODMAPS), which are present in wheat and other gluten-containing and gluten-free foods. New recommendations from the European Society of Paediatrics, Gastroenterology, Hepatology and Nutrition (ESPGHAN) for the diagnosis of celiac disease in children were published in 2020. The diagnosis of gluten intolerance requires the exclusion of celiac disease and wheat allergy.The aim of the study was to determine the characteristics of the clinical course of celiac disease and gluten intolerance (analysis of intestinal and extraintestinal symptoms), serological and morphological features for differential diagnosis and management.Material and methods. Thirty children aged 9 months to 11 years were included in the study for the period 2016-2023. Distribution by gender: 13 (43.3%) boys and 17 (56.6%) girls, p=0.1391. Patients were divided into two groups according to the diagnosis of celiac disease and gluten intolerance. The study included a detailed medical history, assessment of the child's examination and physical development. Determination of titer of IgA antibodies, IgA to tissue transglutaminase (tTG-IgA), endomysial IgA (EMA-IgA), gliadin IgG, wheat IgE antibodies, endoscopy and morphological examination of duodenal mucosal biopsies. Descriptive analysis and comparison of two proportions were used. Non-parametric methods were used to test hypotheses. Logistic regression analysis using the relative risk index (RR) and its 95% confidence interval (CI). Differences in parameters were considered statistically significant when p&lt;0.05.The study was approved by the Commission on Biomedical Ethics for Compliance with Moral and Legal Rules of Medical-Scientific Research of the Kharkiv National Medical University. It was confirmed that the research does not contradict the basic bioethical norms and complies with the main provisions of the Good Clinical Practice (1996), the Convention of the Council of Europe on Human Rights and Biomedicine (04.04.1997), the Declaration of Helsinki of the World Medical Association on the ethical principles of research involving human subjects (1964-2008), and the Order of the Ministry of Health of Ukraine No. 690 (23.09.2009) with amendments according to the Order of the Ministry of Health of Ukraine No. 523 (12.07.2012). Both parents of the patients were informed about the purpose and procedures of the research and signed the informed consent for their children's participation in this study.Statistical analysis was performed using Statistica 7.0 StatSoft Inc.1984-2004, (serial number 12255555555, USA) and MedCalc version 14.8-© 1993-2014 MedCalc Software bvba (Acacialaan 22 B-8400 Ostend, Belgium). The procedures, logic and interpretation of the statistical parameters obtained in the mathematical and statistical analysis were based on generally accepted rules of medical and biological statistics. Descriptive analysis and comparison of two proportions were used. Non-parametric methods were used to test hypotheses: Logistic regression analysis using the relative risk index (RR) and its 95% confidence interval (CI). Differences in parameters were considered statistically significant if p&lt;0.05. Patients in the study were divided into two groups according to the diagnosis of celiac disease and gluten intolerance.The presented article is a fragment of the scientific research of the Department of Paediatrics No.1 and Neonatology of the Kharkiv National Medical University: topic "Medical and social adaptation aspects of children with somatic pathology in modern conditions"; state registration No.0120U102471.Results. 66.6% of children from the general cohort were diagnosed with celiac disease and 33.3% of children with gluten intolerance, p=0.0053. The mean age of the children with celiac disease was 8.4±1.0 years. Gender distribution of children with celiac disease - 50.0% boys, 50.0% girls, p=1.0000. The mean age of the children with gluten intolerance was 9.1±1.0 years. The gender distribution of children with gluten intolerance was 70.0% boys and 30.0% girls, p=0.0001. In 65.0% of children with celiac disease, the diagnosis was confirmed at an earlier stage than in children with gluten intolerance, p=0.0350. A family history of autoimmune pathology was found in 40% of children with celiac disease. All patients with celiac disease were seropositive for serological biomarkers. IgA to tissue transglutaminase tTG-IgA was detected in 95.0% of children with celiac disease (RR=20.4; 95% CI 1.4-307.2; p=0.0292).Diarrhoea and abdominal pain were found in 18/30 children from the general cohort (RR=0.8; 95% CI 0.4-1.4; p=0.5050), loss of appetite - in 17/30 children (RR=0.7; 95% CI 0.4-1.3; p=0. 2695), 15/30 children had constipation and poor weight gain (RR=0.7; 95% CI 0.3-1.5; p=0.4209), 14/30 children had delayed physical development and weakness (RR=0.9; 95% CI 0.4-1.9; p=0.7929). One third of the children had hyperactivity and attention deficit syndrome, sleep disturbances. All children with celiac disease had various stages of small intestinal mucosal atrophy according to the Marsh-Oberhuber classification. No atrophic changes in the small intestinal mucosa were found in children with gluten intolerance (normal structure of villi and crypts), but infiltrative changes were found in 60% of these patients (increase in intraepithelial lymphocytes).Conclusion. Comparative analysis showed no significant differences in the clinical presentation of celiac disease and gluten intolerance. Autoimmune pathology was not found in the family history of children with celiac disease, whereas it was found in 40% of patients with celiac disease. The diagnosis of gluten intolerance is made in case of exclusion of family history of autoimmune nosology; absence of autoantibodies to tissue tranglutaminase and deaminated gliadin peptides, endomysial autoantibodies, which should be determined on a gluten-containing diet, and absence of specific IgE to wheat. All children with celiac disease had various stages of atrophy of the small intestinal mucosa according to the Marsh-Oberhuber classification, whereas no atrophic changes were found in children with gluten intolerance, but 60% of patients with gluten intolerance had infiltrative changes in the small intestinal mucosa.

Covering the Cover

Celiac disease, or gluten-sensitive enteropathy, is a chronic autoimmune disease characterized by immune response when taking gluten. Celiac disease is a multifactorial disorder that results from the interaction of genetic and environmental factors. The review examines the etiology and pathogenesis of celiac disease from the view of the oral mucosal lesions. Based on the data of medical literature sources, the analysis of the incidence, severity and structure of oral cavity changes in celiac disease was conducted. It has been shown that tooth enamel defects and recurrent aphthous stomatitis may be the only manifestation of celiac disease The most common oral cavity disorders in celiac disease are recurrent aphthous stomatitis, teething retention, tooth enamel defects, in particular hypoplasia. Angular cheilitis and atrophic glossitis are considered the very rare. The caries prevalence in patients diagnosed with celiac disease either does not differ from the prevalence in healthy patients, or the caries prevalence indices are significantly lower in patients with celiac disease than in the control group. Oral lesions in celiac disease can cause significant functional and aesthetic disorders, as well as worsen the patient’s life quality. KEYWORDS: celiac disease, gluten enteropathy, oral mucosa, caries, recurrent aphthous stomatitis, teething retention, cheilitis, atrophic glossitis FOR CITATION: Mazurov V.I., Gaydukova I.Z., Inamova O.V. et al. Diseases of the oral mucosa and dental tissues as a manifestation of celiac disease. Russian Medical Inquiry. 2022;6(8):451–457 (in Russ.). DOI: 10.32364/2587-6821-2022-6-8-451-457.

Celiac disease in patients with sporadic and inherited cardiomyopathies and in their relatives.