Everything You Need to Know About Celiac Disease

Celiac disease (CD) is a global condition affecting about 1% of the population, according to the World Health Organization (WHO). This condition occurs in genetically susceptible individuals who develop an immune response triggered by gluten ingestion in response to poorly understood environmental factors (1). 

In Brazil, it is estimated that the prevalence of individuals affected by celiac disease is approximately 2 million, making it one of the most common chronic food-related conditions and, therefore, a considerable public health concern. 

What is Celiac Disease?

It is a chronic immune-mediated disease (when the body generates an abnormal inflammatory response triggered by a foreign antigen), and an enteropathy of the small intestine, occurring in genetically susceptible individuals exposed to gluten (2). 

Celiac disease is triggered by the ingestion of gluten, present in wheat, rye, barley, and their derivatives, which stimulate the immune system to produce antibodies, resulting in lesions in the small intestine mucosa, villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis, through mechanisms that are increasingly being understood (3). 

The human intestine is internally lined with villi that facilitate absorption. The villi have a base called the lamina propria, formed by blood and lymphatic vessels, which receive the products obtained through the digestion process. 

Thus, in individuals genetically predisposed to celiac disease, gluten activates immunological and inflammatory mechanisms that lead to villous atrophy, resulting in a damaged mucosa and reduced surface area for nutrient absorption (4). 

What Causes Celiac Disease? 

Celiac disease occurs due to the inability of gastrointestinal enzymes to break down gluten proteins, leading to an intestinal inflammatory process with consequent malabsorption of nutrients (5). 

This digestive inability is caused by the high proline content in gluten, which gives rise to oligopeptides (gliadin peptides) recognized by the immune system, specifically by T lymphocytes. These induce immune responses in celiac disease patients, leading to increased intestinal permeability and various associated symptoms (6). 

The peptides serve as substrates for the endogenous enzyme TG2 (autoantigen associated with celiac disease), which catalyzes their deamidation, converting specific glutamine residues into glutamic acid. 

Deamidation increases the binding affinity of the gluten peptide to the heterodimers (protein composed of two different subunits) of the human histocompatibility complex, or Human Leukocyte Antigen (HLA) system, specifically to the HLA-DQ2 and HLA-DQ8 alleles, which predispose to celiac disease. 

HLA receptors are expressed on antigen-presenting cells (APCs), such as macrophages and B lymphocytes. This process explains why these two specific HLA haplotypes confer the greatest genetic susceptibility to celiac disease (7). 

Thus, individuals with genetic susceptibility exposed to gluten significantly increase their risk of developing celiac disease. Although immunological and environmental factors can also influence the onset of the disease (8). 

What is Gluten? 

Gluten is a complex mixture of many proteins with similar amino acid sequences. It is the main protein component of wheat (about 70%), being an important structural component of the cereal (9), and it is the substance that remains when wheat flour is washed to remove starch. 

Gluten and its counterparts are proteins rich in proline and glutamine (e.g., prolamins), and the high proline content makes them quite resistant to gastrointestinal digestion. However, due to their unique viscoelastic properties, gluten is essential for dough formation and is a crucial and ubiquitous ingredient in the food industry (10).

What Are the Symptoms of Celiac Disease?

Celiac disease symptoms can develop in childhood or only during adulthood. However, a minority of affected individuals may be apparently asymptomatic (2). 

Patients can exhibit a wide range of symptoms, classified as classical or gastrointestinal and non-classical or extraintestinal, which differ in severity depending on how much the intestine has been affected (11,12). 

The most common gastrointestinal symptoms are: 

• Diarrhea 
• Abdominal pain 
• Constipation 
• Flatulence 
• Loss of appetite 
• Weight loss 
• Steatorrhea (fat in stools) 
• Abdominal distension 
• Growth delay 

Non-classical or extraintestinal symptoms are more prevalent in adults and may be present in about 50% of cases. 

The most common extraintestinal symptoms are: 

• Anemia 
• Osteoporosis 
• Vitamin deficiencies 
• Psychological changes such as anxiety and depression 
• Liver changes that can range from mild elevation of liver enzymes to cirrhosis 
• Endocrine changes such as short stature and type 1 diabetes 
• Dermatological manifestations (dermatitis herpetiformis) 
• Neurological manifestations such as headache, neuropathy, cerebellar ataxia, and gluten encephalopathy 

The variability of symptoms can also influence the time it takes to diagnose the disease. The average time to diagnosis in adults is 2-3 months for those with gastrointestinal symptoms, compared to 42 months for those without gastrointestinal symptoms (13). 

What are the types of celiac disease? 

There are four classifications of celiac disease, according to the symptoms and clinical manifestations found (14,15): 

Classical Form 

This form includes signs of malabsorption accompanied by chronic diarrhea with abdominal distension and weight loss. Other symptoms such as loss of appetite, mood changes, vomiting, and anemia may also be present. When there is a delay in diagnosis and treatment, this form can progress to celiac crisis, often triggered by infection. 

Non-Classical or Atypical Form 

Characterized by a clinical presentation where digestive manifestations are absent or, when present, are secondary. Extraintestinal symptoms are predominant and often identified in isolation (such as short stature, osteoporosis, arthritis, myopathy, among others). 

Silent Form 

Individuals do not present symptoms, but there are serological and histological changes in the small intestine mucosa compatible with celiac disease. 

Latent Form 

This form shows positive serology and absence of villous atrophy in the intestinal biopsy. Patients may develop symptoms and/or histological changes later. 

Difference between gluten intolerance and celiac disease 

Gluten intolerance, also known as non-celiac gluten sensitivity, is a syndrome characterized by the presence of gastrointestinal and extraintestinal symptoms resulting from the ingestion of gluten-containing foods. However, it lacks a known immunological involvement, and the symptoms improve with the exclusion of these foods (16). 

What tests are used to diagnose celiac disease? 

Diagnostic criteria for celiac disease have evolved from requiring three sequential small intestine biopsies to a combination of specific serological tests and the presence of enteropathy in small intestine biopsies, applicable to both children and adults. 

In general, the diagnosis is based on a combination of histological evaluation, serological tests, and assessment of genetic predisposition (17). 

Histological Evaluation 

Upper digestive endoscopy with biopsy remains a critical component for confirming the diagnosis of celiac disease in the majority of cases. A tissue sample is taken from the lining of the small intestine. 

The diagnosis is confirmed if the biopsy shows that the intestinal villi are flattened and if the small intestine improves after the person stops consuming gluten-containing foods (18). 

Serological Antibody Evaluation

Individuals with suggestive symptoms or at increased risk of developing celiac disease are evaluated for the presence of specific antibodies, such as anti-transglutaminase (TTG or TG2), anti-endomysial (EMA), anti-gliadin (AGA), and less frequently, anti-tissue transglutaminase (anti-tTG-ab) and deamidated gliadin peptides (anti-DGP-ab) antibodies (19). 

However, negative serology results do not completely exclude celiac disease. 

Genetic Predisposition Evaluation

Genetic screening involves assessing the risk of developing the disease through genotyping of the HLA genes. The combination of HLA alleles (HLA-DQ2 and HLA-DQ8) explains approximately 40% of the genetic variation of celiac disease. 

However, 30% of the general population (healthy individuals) carry the HLA-DQ2 and/or DQ8 haplotypes, so a positive result does not confirm the diagnosis. Clinical history and other tests need to be evaluated. On the other hand, a negative result for both haplotypes makes the diagnosis of celiac disease very unlikely. 

HLA-DQ2/DQ8 genotyping is useful in early investigation in children (without the need for endoscopy), in screening risk groups, such as in the case of Down syndrome, patients with type 1 diabetes, and patients with first-degree relatives with celiac disease (in these cases, serology and biopsy testing is indicated only if they are positive for HLA-DQ2 and/or DQ8) and to exclude the possibility of celiac disease in certain clinical scenarios (18, 20).

What tests does SYNLAB offer for celiac disease? 

In addition to serological tests for evaluating the main antibodies related to celiac disease (such as anti-transglutaminase and anti-gliadin), SYNLAB offers the following tests: 

Celia Test: This test investigates genetic susceptibility by analyzing the HLA-DQ2 and HLA-DQ8 risk haplotypes. From a patient’s blood sample, DNA is extracted and then amplified by Multiplex-Fluorescent PCR (MF-PCR) of the DQA10501 and DQB10201 alleles of the HLA-DQ2 haplotype and the DQA10301 and DQB10302 alleles of the HLA-DQ8 haplotype. 

INTOLERANCE2: This test allows for a single analysis to determine if there is a genetic predisposition for celiac disease and/or primary lactose intolerance. Unlike the breath test, the analysis is performed using a blood sample, avoiding direct exposure of the patient to substances. 

Wellness Check: This molecular test identifies not only the genetic predisposition for celiac disease but also for the regulation of metabolism and other nutrition-related processes. The genetic analysis determines genetic variants in 24 genes related to: cholesterol and lipid profile; lactose intolerance; celiac disease; salt sensitivity; alcohol metabolism; caffeine metabolism; osteoporosis risk; liver detoxification; oxidative stress; inflammatory response; and homocysteine metabolism. 

What Is the Treatment for Celiac Disease?

The strict and permanent exclusion of all gluten-containing foods from the diet is the only recommended treatment for celiac disease, which generally results in the improvement or resolution of enteropathy and symptoms (21). 

Early adoption of a gluten-free diet has been shown to reduce or eliminate symptoms, halt the progression of many complications related to celiac disease, normalize metabolic and nutritional disorders, and improve weight (22). 

However, studies suggest that not all patients respond to the diet, either symptomatically or histologically, mainly due to inadvertent gluten exposure (23).

Adherence to a gluten-free diet can have negative social consequences. Eating out or traveling is also complicated by the difficulty of accessing gluten-free foods and the constant fear of possible gluten contamination. 

Besides the psychological effects, a gluten-free diet is a financial burden, as most gluten-free products are two to three times more expensive than those containing gluten (24). 

In addition to fruits, vegetables, legumes, meats, eggs, and dairy, corn, buckwheat, rice, quinoa, soy, sorghum, tapioca, and flax are naturally gluten-free grains and therefore suitable for patients with celiac disease. 

About SYNLAB Group

Performing precise and up-to-date tests is essential to achieve more accurate diagnoses and better treatment direction. 

SYNLAB offers diagnostic solutions with rigorous quality control to companies, patients, and doctors. With over 10 years in Brazil, SYNLAB operates in 36 countries and across three continents, leading in service provision in Europe. 

Contact the SYNLAB team to learn about the available tests. 

References on Celiac Disease:

(1) Singh P, Arora A, Strand TA, et al. Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2.

(2) Ludvigsson JF, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013; 62,43–52.

(3) Tye-Din JA, Galipeau HJ, Agardh D. Celiac disease: a review of current concepts in pathogenesis, prevention, and novel therapies. Front. Pediatr. 2018: 6,350.

(4) Farrell R, Kelly, C. Celiac Disease and Refractory Celiac Disease. In: MARK FELDMAN, L.S.F.E.L.J.B. (ed.) Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. Philadelphia: Elsevier. 2010.

(5) Shan L, et al. Structural basis for gluten intolerance in celiac sprue. Science. 2002; 297, 2275–2279.

(6) Cardoso-Silva D, et al. Intestinal barrier function in gluten-related disorders. Nutrients. 2019; 11, 2325.

(7) Kuja-Halkola R, et al. Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins. Gut. 2016; 65,1793–1798.

(8) Bessa CC, et al. Health control for celiac patients: an analysis according to the Pender Health Promotion model, Texto & contexto enfermagem. 2020, 29: e2080420.

(9) Kasarda DD. Can an increase in celiac disease be attributed to an increase in the gluten contente of wheat as a consequence of wheat breeding? J. Agric. Food Chem. 2013; 61, 1155–1159.

(10) Baggus EMR, et al. How to manage adult coeliac disease: perspective from the NHS England rare diseases collaborative network for non-responsive and refractory coeliac disease. Frontline Gastroenterol. 2019; 11,235–242.

(11) Therrien A, et al. Celiac disease: extraintestinal manifestations and associated conditions. Journal of Clinical Gastroenterology. 2020; 54(1):8.

(12) Murphy AK, et al. Celiac Disease in an Adult Presenting as Behavioral Disturbances. The American Journal of Case Reports. 2020; 21:e928337.

(13) Paez MA, et al. Delay in diagnosis of celiac disease in patients without gastrointestinal complaints. The American Journal of Medicine. 2017; 130(11): 1318-1323.

(14) Sdepanian VL, et al. Doença celíaca: avaliação da obediência à dieta isenta de glúten e do conhecimento da doença pelos pacientes cadastrados na Associação dos Celíacos do Brasil (ACELBRA). Arquivos de Gastroenterologia. 2001; 38(4):232-239.

(15) Marques ETF, et al. Uma análise acerca das características da Doença Celíaca: revisão de literatura. Revista Eletrônica Acervo Médico. 2022;15. https://doi.org/10.25248/reamed.e10722.2022.

(16) Sapone A, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. Bmc Medicine. 2012; 10(13).

(17) McNeish AS, Harms HK, Rey J, et al. The diagnosis of coeliac disease. A Commentary on the Current Practices of Members of the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN). Arch Dis Child. 1979;54:783–786.

(18) Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108:656–676.

(19) Giersiepen K, Lelgemann M, Stuhldreher N, et al. Accuracy of diagnostic antibody tests for coeliac disease in children: summary of an evidence report. J Pediatr Gastroenterol Nutr. 2012; 54:229–241.

(20) Husby S, Koletzko S, Korponay-Szabo IR, et al. European society for pediatric gastroenterology, hepatology and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012; 54:136–160.

(21) Baggus EMR, et al. How to manage adult coeliac disease: perspective from the NHS England rare diseases collaborative network for non-responsive and refractory coeliac disease. Frontline Gastroenterol. 2019;11:235–242.

(22) Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American society for pediatric gastroenterology, hepatology and nutrition. J Pediatr Gastroenterol Nutr. 2005;40:1–19.

(23) Daveson AJM, et al. Baseline quantitative histology in therapeutics trials reveals villus atrophy in most patients with coeliac disease who appear well controlled on gluten-free diet. GastroHep. 2020; 2:22–30.

(24) Lee AR, Ng DL, Zivin J, et al. Economic burden of a gluten-free diet. J Hum Nutr Diet. 2007;20:423–430.

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