Coeliac Disease: Clinical Key Findings and Practical Insights

What is a notable characteristic of the symptoms of Coeliac Disease?

What is the ratio of females to males affected by Coeliac Disease?

Which of the following is associated with Coeliac Disease?

What is a characteristic of Coeliac Disease in relation to age?

What is a genetic aspect of Coeliac Disease?

What is the global trend of Coeliac Disease?

What is the estimated percentage of individuals with genotype combinations that confer a high risk of CD who will actually develop a clinical presentation of CD?

What is the primary function of tissue transglutaminase enzyme (t-TG) in the pathophysiology of CD?

What is the characteristic of gluten that makes it resistant to pepsin degradation in the gut?

What is the estimated percentage of clinically silent CD patients in some study populations?

What is the primary mechanism of CD induction in genetically susceptible individuals?

What is the effect of HLA-DQ2 and/or DQ8 on the immune response in CD?

What is the characteristic of CD that makes it a multifactorial disease?

What is the effect of lockdowns and strong counseling to avoid infections on CD diagnoses, especially in children?

What is the primary function of peptic enzymes in the pathophysiology of CD?

What is the characteristic of CD that makes it a systemic autoimmune disorder?

Definition and Epidemiology of Coeliac Disease

Coeliac disease (CD) is a multifactorial, systemic autoimmune disorder characterized by gluten reactivity in genetically predisposed individuals.
CD is a worldwide endemic, with a frequency that is increasing, particularly in developing countries.
The prevalence of CD is generally higher in females than males, with a maximum of 3:1 ratio.

Clinical Presentation and Symptoms

CD can present with classical symptoms, such as chronic diarrhea and malabsorption, or with associated conditions like dental enamel defects, iron deficiency anemia, osteoporosis, recurrent abortion, or infertility.
Some patients may have minimal symptoms or be asymptomatic, making diagnosis challenging.
The symptoms of CD differ greatly with respect to age and individual.

Genetic Factors and Environmental Triggers

Patients with CD show an association with several genetic markers, including HLA-DQA and HLA-DQB genes, indicating a polygenic and monogenic component.
The importance of HLA genes in conferring disease susceptibility is highlighted by the near 100% concordance for CD among monozygotic twins with the DQ2/DQ8 genotype.
Environmental factors, such as changes in food preparation and social habits, may contribute to the increasing frequency of CD diagnoses.

Pathophysiology of Coeliac Disease

The intake of gluten-containing foods by susceptible individuals leads to the occurrence of CD, with the presence of HLA-DQ2/DQ8 and/or HLA epitopes on gluten.
An immunological cascade starts with innate immune activation by tissue transglutaminase 2 (tTG2) through its deamidation activity, resulting in increased celiac-specific peptide generation and recognition by HLA-DQ2 and/or DQ8.
The adaptive immune response against deamidated gluten peptides leads to progressive damage of intestinal tissue.