Causal influence of celiac disease on the risk of sarcoidosis: A Mendelian randomization study.

Observational research shows a link between celiac disease (CeD) and sarcoidosis, but the causal link between CeD and sarcoidosis is still unknown. A two-sample Mendelian randomization (MR) study was conducted to ascertain the causal connection between the 2 disorders. In our two-sample MR analysis, we identified independent genetic variants associated with CeD using publicly accessible GWAS data from people of European ancestry. Summary data for sarcoidosis were obtained from the FinnGen Consortium, the UK-Biobank, and a large GWAS dataset. To assess the association between CeD and sarcoidosis, our MR analysis used inverse variance weighted (IVW) as the primary method, incorporating the MR-Egger, weighted median (WM), and MR-PRESSO (outliers test) as a complementary method. In order to ensure that the findings were reliable, several sensitivity analyses were performed. Our study indicated that CeD had a significant causal relationship with sarcoidosis (IVW odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.07-1.20, P = 5.58E-05; WM OR = 1.12, 95% CI: 1.03-1.23, P = 1.03E-02; MR-Egger OR = 1.07, 95% CI: 0.96-1.19, P = 2.20E-01). Additionally, we obtain the same results in the duplicated datasets as well, which makes our results even more reliable. The results of this investigation did not reveal any evidence of horizontal pleiotropy or heterogeneity. Our MR analysis showed a causal effect between CeD and an elevated risk of sarcoidosis. Further study is still needed to confirm the findings and look into the processes underlying these relationships.

Celiac Disease: A Review from Genetic to Treatment.

Celiac disease (CD) is a complex disorder influenced by genetic and environmental factors. When people with a genetic predisposition to CD consume gluten, an inflammatory response is triggered in the small intestine, and this reaction can be alleviated by the elimination of gluten from the diet. The clinical manifestations of CD vary greatly from person to person and begin at a young age or in adulthood. Influence of genetic factors on CD development is evident in carriers of the DQ2 and/or DQ8 allele. HLA genotypes are associated with gut colonization by bacteria, particularly in individuals suffering from CD. In addition, beneficial gut microbes are crucial for the production of DPP-4, which plays a key role in immune function, as well as metabolic and intestinal health. Therefore, probiotics have been recommended as a complementary food supplement in CD.

Evaluation of HLA-DQ2 and HLA-DQ8 haplotypes in patients with endometriosis, A case-control study.

OBJECTIVE: To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women. METHOD: A retrospective cross-sectional study, was conducted in a Tertiary hospital. PATIENTS: Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis. INTERVENTION: The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers. RESULTS: A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location. CONCLUSION: Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.

Intestinal mRNA expression analysis of polarity-related genes identified the discriminatory ability of CRB3 as a diagnostic marker for celiac disease.

BACKGROUND: Celiac disease (CD) is a chronic autoimmune disorder characterized by an abnormal immune response to gluten, a protein found in wheat, barley, and rye. It is well established that the integrity of epithelial tight junctions (TJs) and adherens junctions (AJs) plays a crucial role in the pathogenesis of CD. These junctional complexes contribute to the apical-basal polarity of the intestinal epithelial cells, which is crucial for their proper functioning. METHODS: Sixty CD subjects, and 50 controls were enrolled in the current study. Mucosal samples were obtained from the distal duodenum, total RNA was extracted and complementary DNA was synthesized. The relative expression levels of the desired genes were evaluated by quantitative real-time polymerase chain reaction based on ΔΔCt method. The gene-gene interaction network was also constructed using GeneMANIA. RESULTS: CRB3 (p = .0005), LKB1 (p < .0001), and SCRIB (p = .0005) had lower expression in CD patients compared to controls, while PRKCZ expression did not differ between groups (p > .05). CRB3 represented a significant diagnostic value for differentiating CD patients from the control group (p = .02). CONCLUSION: The aim of the current study was to evaluate the changes in the mRNA expression levels of SCRIB, PRKCZ, LKB1, and CRB3 genes in the small intestinal biopsy samples of CD patients in comparison to the healthy control subjects. Our data uncover the importance of polarity-related genes (especially CRB3) in CD pahtomechanism, that may facilitate the planning of the future studies looking for finding innovative diagnostic and therapeutic strategies for CD.

Evaluating CD4 and Foxp3 mRNA Expression in Tissue Specimens of Celiac Disease and Colorectal Cancer Patients.

OBJECTIVE: Celiac disease (CD) and colorectal cancer (CRC) are distinct gastrointestinal conditions with a debated association. This study aimed to evaluate the mRNA expression of CD4 and Foxp3 in tissue specimens of CD and CRC patients. The findings can provide valuable insights into the complex connection between these different gastrointestinal conditions. METHODS: Tissue samples from 100 CRC patients, 50 CD patients, and 50 healthy controls (HCs) were collected. RNA extraction, cDNA synthesis, and quantitative real-time PCR were performed. Statistical analysis was conducted using ANOVA and Pearson's correlation test. RESULT: CD4 mRNA expression was significantly higher in CRC patients compared to CD patients and HCs (P<0.0001 for both). Foxp3 mRNA expression was significantly higher in CD patients compared to CRC patients and HCs (P<0.0001 for both). Clinicopathological characteristics did not correlate significantly with gene expression levels. CONCLUSION: This study reveals differential expression patterns of CD4 and Foxp3 mRNA in CRC and CD patients. Upregulated CD4 mRNA suggests its potential role in promoting tumor growth, while increased Foxp3 mRNA expression may reflect an immunosuppressive mechanism in CD pathogenesis. These findings provide insights into the molecular and immunological aspects of CRC and CD, warranting further studies for potential therapeutic strategies.

Saliva direct PCR protocol for HLA-DQB1*02 genotyping.

Celiac disease (CD) is an immune disorder, that is triggered by gluten ingestion in genetically predisposed individuals. The HLA-DQB1*02 allele is the main predisposing genetic factor and a candidate for first-line genotyping screening. We designed and validated a simple, DNA purification-free PCR protocol directly from crude saliva, enabling the detection of the DQB1*02 allele. This assay also distinguishes homozygous from heterozygous carriers. We propose this method for use in mass screening and/or epidemiological studies.

Investigating the role of iron status in the development of coeliac disease: a Mendelian randomisation study.

OBJECTIVE: The environmental trigger behind the increasing prevalence of coeliac disease is not known. One suggested cause is iron deficiency, which is common in coeliac disease. We aimed to evaluate this possible association with Mendelian randomisation (MR), which under certain assumptions can suggest a causal relationship. DESIGN: We conducted a two-sample MR study examining the relationship between single nucleotide polymorphisms (SNPs) associated with iron status and the presence of coeliac disease. The SNPs were drawn from a meta-analysis of three genome-wide association studies (GWAS). The association between these SNPs and coeliac disease was assessed using GWAS summary statistics from the UK Biobank. This consists of 336 638 white British individuals, 1855 with coeliac disease. We performed an MR Egger test for pleiotropy and assessed the plausibility of the assumptions of MR to evaluate for possible causality. RESULTS: There were four SNPs strongly associated with systemic iron status. These were not associated with known risk factors for coeliac disease. All four SNPs were available in the UK Biobank coeliac disease summary statistics. Harmonising exposure and outcome associations, we found that higher iron status was negatively associated with risk of coeliac disease (OR per 1 SD increase in serum iron: 0.65, 95% CI 0.47 to 0.91). Leave-one-out analyses had consistent results, and no single SNP drove the association. All three assumptions of MR appeared plausible. CONCLUSION: We found that genetically lower iron levels were associated with an increased risk of coeliac disease. Our findings highlight a potential opportunity for coeliac disease prevention.

Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease.

We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules involved in celiac disease (CD). We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of CD. CD200, CD200R and Elafin distributions were determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the PI3 gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection. We characterized the expression and function of the CD200-CD200R axis and PI3 in celiac disease. A significantly higher level of soluble CD200 and CD200R and lower expression of PI3 in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type-Th1 and -Th17 cytokines. Regarding the PI3 genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752 were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD. In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will lead to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the PI3 gene-splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.

Coeliac disease: what can we learn from prospective studies about disease risk?

Paediatric prospective studies of coeliac disease with longitudinal collection of biological samples and clinical data offer a unique perspective on disease risk. This Review highlights the information now available from international paediatric prospective studies on genetic and environmental risk factors for coeliac disease. In addition, recent omics studies have made it possible to study complex interactions between genetic and environmental factors and thereby further our insight into the causes of the disease. In the future, paediatric prospective studies will be able to provide more detailed risk prediction models combining genes, the environment, and biological corroboration from multiomics. Such studies could also contribute to biomarker development and an improved understanding of disease pathogenesis.

UK NEQAS and BSHI guideline: Laboratory testing and clinical interpretation of HLA genotyping results supporting the diagnosis of coeliac disease.

Coeliac disease is a common immune-mediated inflammatory disorder caused by dietary gluten in genetically susceptible individuals. While the diagnosis of coeliac disease is based on serological and histological criteria, HLA-DQ genotyping can be useful, especially in excluding the diagnosis in patients who do not carry the relevant DQ heterodimers: DQA1*05 DQB1*02, DQB1*03:02 or DQA1*02 DQB1*02 (commonly referred to as DQ2.5, DQ8 and DQ2.2, respectively). External quality assessment results for HLA genotyping in coeliac disease have revealed concerning errors in HLA genotyping, reporting and clinical interpretation. In response, these guidelines have been developed as an evidence-based approach to guide laboratories undertaking HLA genotyping for coeliac disease and provide recommendations for reports to standardise and improve the communication of results.

Sex bias in celiac disease: XWAS and monocyte eQTLs in women identify TMEM187 as a functional candidate gene.

BACKGROUND: Celiac disease (CeD) is an immune-mediated disorder that develops in genetically predisposed individuals upon gluten consumption. HLA risk alleles explain 40% of the genetic component of CeD, so there have been continuing efforts to uncover non-HLA loci that can explain the remaining heritability. As in most autoimmune disorders, the prevalence of CeD is significantly higher in women. Here, we investigated the possible involvement of the X chromosome on the sex bias of CeD. METHODS: We performed a X chromosome-wide association study (XWAS) and a gene-based association study in women from the CeD Immunochip (7062 cases, 5446 controls). We also constructed a database of X chromosome cis-expression quantitative trait loci (eQTLs) in monocytes from unstimulated (n = 226) and lipopolysaccharide (LPS)-stimulated (n = 130) female donors and performed a Summary-data-based MR (SMR) analysis to integrate XWAS and eQTL information. We interrogated the expression of the potentially causal gene (TMEM187) in peripheral blood mononuclear cells (PBMCs) from celiac patients at onset, on a gluten-free diet, potential celiac patients and non-celiac controls. RESULTS: The XWAS and gene-based analyses identified 13 SNPs and 25 genes, respectively, 22 of which had not been previously associated with CeD. The X chromosome cis-eQTL analysis found 18 genes with at least one cis-eQTL in naïve female monocytes and 8 genes in LPS-stimulated female monocytes, 2 of which were common to both situations and 6 were unique to LPS stimulation. SMR identified a potentially causal association of TMEM187 expression in naïve monocytes with CeD in women, regulated by CeD-associated, eQTL-SNPs rs7350355 and rs5945386. The CeD-risk alleles were correlated with lower TMEM187 expression. These results were replicated using eQTLs from LPS-stimulated monocytes. We observed higher levels of TMEM187 expression in PBMCs from female CeD patients at onset compared to female non-celiac controls, but not in male CeD individuals. CONCLUSION: Using X chromosome genotypes and gene expression data from female monocytes, SMR has identified TMEM187 as a potentially causal candidate in CeD. Further studies are needed to understand the implication of the X chromosome in the higher prevalence of CeD in women.

Celiac disease (CeD) is an immune-related condition triggered by gluten consumption in genetically susceptible individuals. Women present higher prevalence of CeD than men, but the biological explanation of such difference has not been elucidated. In this study, we investigated whether specific genetic variations on the X chromosome were associated with CeD in each sex. Surprisingly, we found 13 genetic variants and 25 genes significantly linked to CeD in women, but not in men. Additionally, we identified genetic variants on the X chromosome associated with gene expression of monocytes, a type of immune cells that is activated in CeD after gluten intake. Integrating these data with our previous findings, we found that lower expression of a gene termed TMEM187 might be associated with a potential increase in CeD risk in women. Finally, validation experiments confirmed higher TMEM187 levels in blood cells from female CeD patients compared to non-celiac women, while no such difference was seen in males. In summary, our study suggests that the X-chromosome gene TMEM187 may play a key role in CeD development, providing insights into the higher prevalence of CeD in females.

A review of the long-term use of proton pump inhibitors and risk of celiac disease in the context of HLA-DQ2 and HLA-DQ8 genetic predisposition.

Proton pump inhibitors (PPIs) are among the most prescribed and widely used medications; however, the long-term effects of these medications are only beginning to be investigated. Since the introduction of omeprazole in 1989, PPIs have become the first-choice treatment for esophagitis, peptic ulcer disease, Zoster-Ellison syndrome, dyspepsia, and the prevention of ulcers with non-steroidal anti-inflammatory drugs. Recent studies have specifically examined the rise in celiac disease (CD) in this context. This review explores how PPIs may impact the development of CD and highlights the need for additional research into the environmental and genetic factors that influence the development and progression of the disease. A literature search was performed using the keywords celiac disease, proton pump inhibitors, human leukocyte antigen (HLA)-DQ2, HLA-DQ8. The pathogenesis of CD is multifactorial, and human leukocyte antigens are one factor that may contribute to its development. Additionally, pharmaceuticals, such as PPIs, that cause gut dysbiosis have been linked to the inflammatory response present in CD. Recent studies have suggested that the rise in CD could be attributed to changes in the gut microbiome, highlighting the significant role that gut microbiota is proposed to play in CD pathogenesis. Although PPI therapy is helpful in reducing acid production in gastroesophageal disorders, additional information is needed to determine whether PPIs are still an appropriate treatment option with the possibility of developing CD in the future, particularly in the context of HLA-DQ2 and HLA-DQ8 predispositions. This review emphasizes the importance of personalized medicine for individuals with gastroesophageal disorders that require long-term use of PPIs.

Influence of genetically predicted autoimmune diseases on NAFLD.

Introduction: Non-alcoholic fatty liver disease (NAFLD), the emerging cause of end-stage liver disease, is the most common liver disease. Determining the independent risk factors of NAFLD and patients who need more monitoring is important. Methods: Two-Sample Mendelian randomization (MR) was performed in the analysis to investigate the causal association of different autoimmune diseases with NAFLD using summary level data. Genome-wide association study (GWAS) of 5 autoimmune diseases including celiac disease (CeD), Crohn's disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), and type 1 diabetes (T1D) were selected for Instrument variables (IVs). NAFLD was included as outcome. Result: After adjusting for confounding factors, genetic predisposition of CeD (OR= 0.973, [0.949,0.997], IVW p-value=0.026), MS (OR= 1.048, [1.012,1.085], IVW p-value= 0.008), RA (OR= 1.036, [1.006,1.066], IVW p-value=0.019), T1D (OR= 1.039, [1.002,1.079], IVW p-value= 0.041) is causally associated with NAFLD. No causal effect was found between CD and NAFLD. Conclusion: CeD itself may be a protective factor for NAFLD, the results of previous observational studies have been influenced by confounding factors, and the morbidity of NAFLD may be higher in patients with MS, RA, and T1D than in common populations, and monitoring the prevalence of NAFLD in these populations is considerable.

Systemic lupus erythematosus is associated with the risk of coeliac disease: a Mendelian randomisation study.

As an autoimmune disease, systemic lupus erythematosus (SLE) can affect multiple organs and systems. Whether SLE can increase the risk of coeliac disease (CeD) was not evaluated until now. We performed a two-sample Mendelian randomisation study to evaluate the relationship between SLE and CeD, and found that SLE can significantly increase the risk of CeD, suggesting the association between SLE and abnormal intestinal immune microenvironment.

Developing neural network diagnostic models and potential drugs based on novel identified immune-related biomarkers for celiac disease.

BACKGROUND: As one of the most common intestinal inflammatory diseases, celiac disease (CD) is typically characterized by an autoimmune disorder resulting from ingesting gluten proteins. Although the incidence and prevalence of CD have increased over time, the diagnostic methods and treatment options are still limited. Therefore, it is urgent to investigate the potential biomarkers and targeted drugs for CD. METHODS: Gene expression data was downloaded from GEO datasets. Differential gene expression analysis was performed to identify the dysregulated immune-related genes. Multiple machine algorithms, including randomForest, SVM-RFE, and LASSO, were used to select the hub immune-related genes (HIGs). The immune-related genes score (IG score) and artificial neural network (ANN) were constructed based on HIGs. Potential drugs targeting HIGs were identified by using the Enrichr platform and molecular docking method. RESULTS: We identified the dysregulated immune-related genes at a genome-wide level and demonstrated their roles in CD-related immune pathways. The hub genes (MR1, CCL25, and TNFSF13B) were further screened by integrating several machine algorithms. Meanwhile, the CD patients were divided into distinct subtypes with either high- or low-immunoactivity using single-sample gene set enrichment analysis (ssGSEA) and consensus clustering. By constructing IG score based on HIGs, we found that patients with high IG score were mainly attributed to high-immunoactivity subgroups, which suggested a strong link between HIGs and immunoactivity of CD patients. In addition, the novel constructed ANN model showed the sound diagnostic ability of HIGs. Mechanistically, we validated that the HIGs play pivotal roles in regulating CD's immune and inflammatory state. Through targeting the HIGs, we also found potential drugs for anti-CD treatment by using the Enrichr platform and molecular docking method. CONCLUSIONS: This study unveils the HIGs and elucidates the networks regulated by these genes in the context of CD. It underscores the pivotal significance of HIGs in accurately predicting the presence or absence of CD in patients. Consequently, this research offers promising prospects for the development of diagnostic biomarkers and therapeutic targets for CD.

Human intestinal organoid models for celiac disease research.

Celiac disease pathogenesis, in addition to immune cell component, encompasses pathogenic events also in the duodenal epithelium. In celiac disease patients, exposure to dietary gluten induces drastic changes in epithelial differentiation and elicit cellular response to inflammatory cytokines. The autoantigen in celiac disease, transglutaminase 2 (TG2) enzyme, has been also suggested to play its pathogenic gliadin deamidation event in the intestinal epithelium. Therefore in vitro epithelial cell-line models have been exploited in the past to study these pathogenic mechanisms, but they are hampered by their simplistic nature lacking proper cell-type composition and intestinal environ. Moreover, these cell models harbor many cancer-related mutations in tumor suppressor genes making them unsuitable for studying cell differentiation. Intestinal organoids provide a near-native epithelial cell model to study pathogenic agents and mechanisms related to celiac disease. Here we describe protocols to initiate and maintain celiac patient-derived organoid cultures and how to grow them in alternative ways allowing their exploitation in different kind of experiments.

A fast, cheap, and easy protocol for celiac disease HLA haplotype typing using buccal swabs.

Celiac disease (CeD) is a complex autoimmune disorder characterized by intestinal immune-derived injury that develops in response to dietary gluten consumption. Human Leucocyte Antigen (HLA) complex haplotype typing is one of the main tests for CeD diagnosis, together with anti-endomysium and anti-transglutaminase autoantibody detection in blood and inflammation observation in the intestine, being the former mainly used for the initial discarding of the pathogenesis. Among the many types of HLA proteins, HLA-DQ2.5 and HLA-DQ8 are considered essential for CeD development. These receptors are only expressed when specific alleles are present, which can be accurately predicted by the presence of the tagging SNPs rs2187668 and rs7454108, respectively. Taking advantage of this premise, we present here an easy workflow to assess HLA genotyping in saliva by a quick and cheap isopropanol-ethanol precipitation-based DNA extraction method followed by the genotyping of two tagging SNPs for the most frequent CeD risk-associated HLA haplotypes. All the actual diagnostic methods for CeD are performed after acquisition of intestine biopsies or blood samples by invasive techniques. Therefore, the development of non-invasive methods would be of a great improvement and advantage for patients, especially children, as an alternative method for initial CeD screening.

In vivo sensitization to gliadin by oral administration.

Celiac disease is a highly prevalent immune-mediated enteropathy that develops in genetically susceptible individuals expressing HLA-DQ2 or HLA-DQ8 after ingestion of gluten and results in decreased quality of life and increased morbidity. This pathology is triggered by immunogenic peptides generated from gliadins present in gluten, which act on the intestinal mucosa in a context of high intestinal permeability, activating the innate and adaptive response of the immune system. Several in vivo rodent models attempt to reproduce some phases of the intestinal inflammatory process that occurs in celiac disease. Allergic sensitization to gluten simulates, or enhances in some animal models, the loss of tolerance to gliadin peptides and the initial events that lead to celiac disease in a specific genetic or environmental context. Here we describe a simple method for performing gliadin sensitization in an in vivo animal model.

Elucidating the role of microbes in celiac disease through gnotobiotic modeling.

Celiac disease (CeD) is a common immune-mediated disease triggered by the ingestion of gluten in genetically predisposed individuals. CeD is unique in that the trigger (gluten), necessary genes (HLA-DQ2 and DQ8), and the autoantigen (tissue transglutaminase) have been identified, allowing additional environmental co-factors, like the intestinal microbiota, to be studied through relevant in vivo models. Murine models for CeD have come a long way in the past decade and there are now in vitro and in vivo tools available that mimic certain aspects of clinical disease. These models, many of which express the CeD risk genes, have recently been used to study the mechanisms through which the microbiota play a role in CeD pathogenesis through a gnotobiotic approach. Historically, the generation of gnotobiology technology in mid-20th century allowed for the study of immunity and physiology under a complete absence of microbes (axenic) or known colonized status (gnotobiotic). This enabled understanding of mechanisms by which certain bacteria contribute to health and disease. With this perspective, here, we will discuss the various murine models currently being used to study CeD. We will then describe how utilizing axenic and gnotobiotic CeD models has increased our understanding of how microbes influence relevant steps of CeD pathogenesis, and explain key methodology involved in axenic and gnotobiotic modeling.

Coeliac Disease High-Risk Human Leukocyte Antigen Alleles in a South African Type One Diabetic Population.

BACKGROUND: Coeliac disease (CD) is an autoimmune disorder strongly associated with Human Leukocyte Antigen (HLA) genes DQ2 and DQ8. These alleles are also associated with other autoimmune diseases including type 1 dia-betes (T1D) and these patients are consequently at a higher risk of developing CD. We examined the frequency of high-risk HLA alleles in a cohort of South African T1D pediatric patients. METHODS: A total of 22 pediatric participants were recruited at an endocrinology clinic in a public sector hospital in Johannesburg, South Africa. Clinical details were collected, and all patients were HLA typed at the DQ loci. RESULTS: Of our T1D patients, 63.6% had at least 1 high-risk HLA type alleles associated with CD. Of the patients with high-risk alleles, DQ2 was found in the majority which is consistent with CD literature. CONCLUSIONS: This study provides preliminary insight into the frequency of the HLA-DQ types associated with CD in a South African population. The high prevalence of high-risk alleles in our T1D population motivates continual monitoring and further investigations into CD in South Africa.